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Raffi Hovasapian

Raffi Hovasapian

Protein Function III: More on Hemoglobin

Slide Duration:

Table of Contents

I. Preliminaries on Aqueous Chemistry
Aqueous Solutions & Concentration

39m 57s

Intro
0:00
Aqueous Solutions and Concentration
0:46
Definition of Solution
1:28
Example: Sugar Dissolved in Water
2:19
Example: Salt Dissolved in Water
3:04
A Solute Does Not Have to Be a Solid
3:37
A Solvent Does Not Have to Be a Liquid
5:02
Covalent Compounds
6:55
Ionic Compounds
7:39
Example: Table Sugar
9:12
Example: MgCl₂
10:40
Expressing Concentration: Molarity
13:42
Example 1
14:47
Example 1: Question
14:50
Example 1: Solution
15:40
Another Way to Express Concentration
22:01
Example 2
24:00
Example 2: Question
24:01
Example 2: Solution
24:49
Some Other Ways of Expressing Concentration
27:52
Example 3
29:30
Example 3: Question
29:31
Example 3: Solution
31:02
Dilution & Osmotic Pressure

38m 53s

Intro
0:00
Dilution
0:45
Definition of Dilution
0:46
Example 1: Question
2:08
Example 1: Basic Dilution Equation
4:20
Example 1: Solution
5:31
Example 2: Alternative Approach
12:05
Osmotic Pressure
14:34
Colligative Properties
15:02
Recall: Covalent Compounds and Soluble Ionic Compounds
17:24
Properties of Pure Water
19:42
Addition of a Solute
21:56
Osmotic Pressure: Conceptual Example
24:00
Equation for Osmotic Pressure
29:30
Example of 'i'
31:38
Example 3
32:50
More on Osmosis

29m 1s

Intro
0:00
More on Osmosis
1:25
Osmotic Pressure
1:26
Example 1: Molar Mass of Protein
5:25
Definition, Equation, and Unit of Osmolarity
13:13
Example 2: Osmolarity
15:19
Isotonic, Hypertonic, and Hypotonic
20:20
Example 3
22:20
More on Isotonic, Hypertonic, and Hypotonic
26:14
Osmosis vs. Osmotic Pressure
27:56
Acids & Bases

39m 11s

Intro
0:00
Acids and Bases
1:16
Let's Begin With H₂O
1:17
P-Scale
4:22
Example 1
6:39
pH
9:43
Strong Acids
11:10
Strong Bases
13:52
Weak Acids & Bases Overview
14:32
Weak Acids
15:49
Example 2: Phosphoric Acid
19:30
Weak Bases
24:50
Weak Base Produces Hydroxide Indirectly
25:41
Example 3: Pyridine
29:07
Acid Form and Base Form
32:02
Acid Reaction
35:50
Base Reaction
36:27
Ka, Kb, and Kw
37:14
Titrations and Buffers

41m 33s

Intro
0:00
Titrations
0:27
Weak Acid
0:28
Rearranging the Ka Equation
1:45
Henderson-Hasselbalch Equation
3:52
Fundamental Reaction of Acids and Bases
5:36
The Idea Behind a Titration
6:27
Let's Look at an Acetic Acid Solution
8:44
Titration Curve
17:00
Acetate
23:57
Buffers
26:57
Introduction to Buffers
26:58
What is a Buffer?
29:40
Titration Curve & Buffer Region
31:44
How a Buffer Works: Adding OH⁻
34:44
How a Buffer Works: Adding H⁺
35:58
Phosphate Buffer System
38:02
Example Problems with Acids, Bases & Buffers

44m 19s

Intro
0:00
Example 1
1:21
Example 1: Properties of Glycine
1:22
Example 1: Part A
3:40
Example 1: Part B
4:40
Example 2
9:02
Example 2: Question
9:03
Example 2: Total Phosphate Concentration
12:23
Example 2: Final Solution
17:10
Example 3
19:34
Example 3: Question
19:35
Example 3: pH Before
22:18
Example 3: pH After
24:24
Example 3: New pH
27:54
Example 4
30:00
Example 4: Question
30:01
Example 4: Equilibria
32:52
Example 4: 1st Reaction
38:04
Example 4: 2nd Reaction
39:53
Example 4: Final Solution
41:33
Hydrolysis & Condensation Reactions

18m 45s

Intro
0:00
Hydrolysis and Condensation Reactions
0:50
Hydrolysis
0:51
Condensation
2:42
Example 1: Hydrolysis of Ethyl Acetate
4:52
Example 2: Condensation of Acetic Acid with Ethanol
8:42
Example 3
11:18
Example 4: Formation & Hydrolysis of a Peptide Bond Between the Amino Acids Alanine & Serine
14:56
II. Amino Acids & Proteins: Primary Structure
Amino Acids

38m 19s

Intro
0:00
Amino Acids
0:17
Proteins & Amino Acids
0:18
Difference Between Amino Acids
4:20
α-Carbon
7:08
Configuration in Biochemistry
10:43
L-Glyceraldehyde & Fischer Projection
12:32
D-Glyceraldehyde & Fischer Projection
15:31
Amino Acids in Biological Proteins are the L Enantiomer
16:50
L-Amino Acid
18:04
L-Amino Acids Correspond to S-Enantiomers in the RS System
20:10
Classification of Amino Acids
22:53
Amino Acids With Non-Polar R Groups
26:45
Glycine
27:00
Alanine
27:48
Valine
28:15
Leucine
28:58
Proline
31:08
Isoleucine
32:42
Methionine
33:43
Amino Acids With Aromatic R Groups
34:33
Phenylalanine
35:26
Tyrosine
36:02
Tryptophan
36:32
Amino Acids, Continued

27m 14s

Intro
0:00
Amino Acids With Positively Charged R Groups
0:16
Lysine
0:52
Arginine
1:55
Histidine
3:15
Amino Acids With Negatively Charged R Groups
6:28
Aspartate
6:58
Glutamate
8:11
Amino Acids With Uncharged, but Polar R Groups
8:50
Serine
8:51
Threonine
10:21
Cysteine
11:06
Asparagine
11:35
Glutamine
12:44
More on Amino Acids
14:18
Cysteine Dimerizes to Form Cystine
14:53
Tryptophan, Tyrosine, and Phenylalanine
19:07
Other Amino Acids
20:53
Other Amino Acids: Hydroxy Lysine
22:34
Other Amino Acids: r-Carboxy Glutamate
25:37
Acid/Base Behavior of Amino Acids

48m 28s

Intro
0:00
Acid/Base Behavior of Amino Acids
0:27
Acid/Base Behavior of Amino Acids
0:28
Let's Look at Alanine
1:57
Titration of Acidic Solution of Alanine with a Strong Base
2:51
Amphoteric Amino Acids
13:24
Zwitterion & Isoelectric Point
16:42
Some Amino Acids Have 3 Ionizable Groups
20:35
Example: Aspartate
24:44
Example: Tyrosine
28:50
Rule of Thumb
33:04
Basis for the Rule
35:59
Example: Describe the Degree of Protonation for Each Ionizable Group
38:46
Histidine is Special
44:58
Peptides & Proteins

45m 18s

Intro
0:00
Peptides and Proteins
0:15
Introduction to Peptides and Proteins
0:16
Formation of a Peptide Bond: The Bond Between 2 Amino Acids
1:44
Equilibrium
7:53
Example 1: Build the Following Tripeptide Ala-Tyr-Ile
9:48
Example 1: Shape Structure
15:43
Example 1: Line Structure
17:11
Peptides Bonds
20:08
Terms We'll Be Using Interchangeably
23:14
Biological Activity & Size of a Peptide
24:58
Multi-Subunit Proteins
30:08
Proteins and Prosthetic Groups
32:13
Carbonic Anhydrase
37:35
Primary, Secondary, Tertiary, and Quaternary Structure of Proteins
40:26
Amino Acid Sequencing of a Peptide Chain

42m 47s

Intro
0:00
Amino Acid Sequencing of a Peptide Chain
0:30
Amino Acid Sequence and Its Structure
0:31
Edman Degradation: Overview
2:57
Edman Degradation: Reaction - Part 1
4:58
Edman Degradation: Reaction - Part 2
10:28
Edman Degradation: Reaction - Part 3
13:51
Mechanism Step 1: PTC (Phenylthiocarbamyl) Formation
19:01
Mechanism Step 2: Ring Formation & Peptide Bond Cleavage
23:03
Example: Write Out the Edman Degradation for the Tripeptide Ala-Tyr-Ser
30:29
Step 1
30:30
Step 2
34:21
Step 3
36:56
Step 4
38:28
Step 5
39:24
Step 6
40:44
Sequencing Larger Peptides & Proteins

1h 2m 33s

Intro
0:00
Sequencing Larger Peptides and Proteins
0:28
Identifying the N-Terminal Amino Acids With the Reagent Fluorodinitrobenzene (FDNB)
0:29
Sequencing Longer Peptides & Proteins Overview
5:54
Breaking Peptide Bond: Proteases and Chemicals
8:16
Some Enzymes/Chemicals Used for Fragmentation: Trypsin
11:14
Some Enzymes/Chemicals Used for Fragmentation: Chymotrypsin
13:02
Some Enzymes/Chemicals Used for Fragmentation: Cyanogen Bromide
13:28
Some Enzymes/Chemicals Used for Fragmentation: Pepsin
13:44
Cleavage Location
14:04
Example: Chymotrypsin
16:44
Example: Pepsin
18:17
More on Sequencing Larger Peptides and Proteins
19:29
Breaking Disulfide Bonds: Performic Acid
26:08
Breaking Disulfide Bonds: Dithiothreitol Followed by Iodoacetate
31:04
Example: Sequencing Larger Peptides and Proteins
37:03
Part 1 - Breaking Disulfide Bonds, Hydrolysis and Separation
37:04
Part 2 - N-Terminal Identification
44:16
Part 3 - Sequencing Using Pepsin
46:43
Part 4 - Sequencing Using Cyanogen Bromide
52:02
Part 5 - Final Sequence
56:48
Peptide Synthesis (Merrifield Process)

49m 12s

Intro
0:00
Peptide Synthesis (Merrifield Process)
0:31
Introduction to Synthesizing Peptides
0:32
Merrifield Peptide Synthesis: General Scheme
3:03
So What Do We Do?
6:07
Synthesis of Protein in the Body Vs. The Merrifield Process
7:40
Example: Synthesis of Ala-Gly-Ser
9:21
Synthesis of Ala-Gly-Ser: Reactions Overview
11:41
Synthesis of Ala-Gly-Ser: Reaction 1
19:34
Synthesis of Ala-Gly-Ser: Reaction 2
24:34
Synthesis of Ala-Gly-Ser: Reaction 3
27:34
Synthesis of Ala-Gly-Ser: Reaction 4 & 4a
28:48
Synthesis of Ala-Gly-Ser: Reaction 5
33:38
Synthesis of Ala-Gly-Ser: Reaction 6
36:45
Synthesis of Ala-Gly-Ser: Reaction 7 & 7a
37:44
Synthesis of Ala-Gly-Ser: Reaction 8
39:47
Synthesis of Ala-Gly-Ser: Reaction 9 & 10
43:23
Chromatography: Eluent, Stationary Phase, and Eluate
45:55
More Examples with Amino Acids & Peptides

54m 31s

Intro
0:00
Example 1
0:22
Data
0:23
Part A: What is the pI of Serine & Draw the Correct Structure
2:11
Part B: How Many mL of NaOH Solution Have Been Added at This Point (pI)?
5:27
Part C: At What pH is the Average Charge on Serine
10:50
Part D: Draw the Titration Curve for This Situation
14:50
Part E: The 10 mL of NaOH Added to the Solution at the pI is How Many Equivalents?
17:35
Part F: Serine Buffer Solution
20:22
Example 2
23:04
Data
23:05
Part A: Calculate the Minimum Molar Mass of the Protein
25:12
Part B: How Many Tyr Residues in this Protein?
28:34
Example 3
30:08
Question
30:09
Solution
34:30
Example 4
48:46
Question
48:47
Solution
49:50
III. Proteins: Secondary, Tertiary, and Quaternary Structure
Alpha Helix & Beta Conformation

50m 52s

Intro
0:00
Alpha Helix and Beta Conformation
0:28
Protein Structure Overview
0:29
Weak interactions Among the Amino Acid in the Peptide Chain
2:11
Two Principals of Folding Patterns
4:56
Peptide Bond
7:00
Peptide Bond: Resonance
9:46
Peptide Bond: φ Bond & ψ Bond
11:22
Secondary Structure
15:08
α-Helix Folding Pattern
17:28
Illustration 1: α-Helix Folding Pattern
19:22
Illustration 2: α-Helix Folding Pattern
21:39
β-Sheet
25:16
β-Conformation
26:04
Parallel & Anti-parallel
28:44
Parallel β-Conformation Arrangement of the Peptide Chain
30:12
Putting Together a Parallel Peptide Chain
35:16
Anti-Parallel β-Conformation Arrangement
37:42
Tertiary Structure
45:03
Quaternary Structure
45:52
Illustration 3: Myoglobin Tertiary Structure & Hemoglobin Quaternary Structure
47:13
Final Words on Alpha Helix and Beta Conformation
48:34
IV. Proteins: Function
Protein Function I: Ligand Binding & Myoglobin

51m 36s

Intro
0:00
Protein Function I: Ligand Binding & Myoglobin
0:30
Ligand
1:02
Binding Site
2:06
Proteins are Not Static or Fixed
3:36
Multi-Subunit Proteins
5:46
O₂ as a Ligand
7:21
Myoglobin, Protoporphyrin IX, Fe ²⁺, and O₂
12:54
Protoporphyrin Illustration
14:25
Myoglobin With a Heme Group Illustration
17:02
Fe²⁺ has 6 Coordination Sites & Binds O₂
18:10
Heme
19:44
Myoglobin Overview
22:40
Myoglobin and O₂ Interaction
23:34
Keq or Ka & The Measure of Protein's Affinity for Its Ligand
26:46
Defining α: Fraction of Binding Sites Occupied
32:52
Graph: α vs. [L]
37:33
For The Special Case of α = 0.5
39:01
Association Constant & Dissociation Constant
43:54
α & Kd
45:15
Myoglobin's Binding of O₂
48:20
Protein Function II: Hemoglobin

1h 3m 36s

Intro
0:00
Protein Function II: Hemoglobin
0:14
Hemoglobin Overview
0:15
Hemoglobin & Its 4 Subunits
1:22
α and β Interactions
5:18
Two Major Conformations of Hb: T State (Tense) & R State (Relaxed)
8:06
Transition From The T State to R State
12:03
Binding of Hemoglobins & O₂
14:02
Binding Curve
18:32
Hemoglobin in the Lung
27:28
Signoid Curve
30:13
Cooperative Binding
32:25
Hemoglobin is an Allosteric Protein
34:26
Homotropic Allostery
36:18
Describing Cooperative Binding Quantitatively
38:06
Deriving The Hill Equation
41:52
Graphing the Hill Equation
44:43
The Slope and Degree of Cooperation
46:25
The Hill Coefficient
49:48
Hill Coefficient = 1
51:08
Hill Coefficient < 1
55:55
Where the Graph Hits the x-axis
56:11
Graph for Hemoglobin
58:02
Protein Function III: More on Hemoglobin

1h 7m 16s

Intro
0:00
Protein Function III: More on Hemoglobin
0:11
Two Models for Cooperative Binding: MWC & Sequential Model
0:12
MWC Model
1:31
Hemoglobin Subunits
3:32
Sequential Model
8:00
Hemoglobin Transports H⁺ & CO₂
17:23
Binding Sites of H⁺ and CO₂
19:36
CO₂ is Converted to Bicarbonate
23:28
Production of H⁺ & CO₂ in Tissues
27:28
H⁺ & CO₂ Binding are Inversely Related to O₂ Binding
28:31
The H⁺ Bohr Effect: His¹⁴⁶ Residue on the β Subunits
33:31
Heterotropic Allosteric Regulation of O₂ Binding by 2,3-Biphosphoglycerate (2,3 BPG)
39:53
Binding Curve for 2,3 BPG
56:21
V. Enzymes
Enzymes I

41m 38s

Intro
0:00
Enzymes I
0:38
Enzymes Overview
0:39
Cofactor
4:38
Holoenzyme
5:52
Apoenzyme
6:40
Riboflavin, FAD, Pyridoxine, Pyridoxal Phosphate Structures
7:28
Carbonic Anhydrase
8:45
Classification of Enzymes
9:55
Example: EC 1.1.1.1
13:04
Reaction of Oxidoreductases
16:23
Enzymes: Catalysts, Active Site, and Substrate
18:28
Illustration of Enzymes, Substrate, and Active Site
27:22
Catalysts & Activation Energies
29:57
Intermediates
36:00
Enzymes II

44m 2s

Intro
0:00
Enzymes II: Transitions State, Binding Energy, & Induced Fit
0:18
Enzymes 'Fitting' Well With The Transition State
0:20
Example Reaction: Breaking of a Stick
3:40
Another Energy Diagram
8:20
Binding Energy
9:48
Enzymes Specificity
11:03
Key Point: Optimal Interactions Between Substrate & Enzymes
15:15
Induced Fit
16:25
Illustrations: Induced Fit
20:58
Enzymes II: Catalytic Mechanisms
22:17
General Acid/Base Catalysis
23:56
Acid Form & Base Form of Amino Acid: Glu &Asp
25:26
Acid Form & Base Form of Amino Acid: Lys & Arg
26:30
Acid Form & Base Form of Amino Acid: Cys
26:51
Acid Form & Base Form of Amino Acid: His
27:30
Acid Form & Base Form of Amino Acid: Ser
28:16
Acid Form & Base Form of Amino Acid: Tyr
28:30
Example: Phosphohexose Isomerase
29:20
Covalent Catalysis
34:19
Example: Glyceraldehyde 3-Phosphate Dehydrogenase
35:34
Metal Ion Catalysis: Isocitrate Dehydrogenase
38:45
Function of Mn²⁺
42:15
Enzymes III: Kinetics

56m 40s

Intro
0:00
Enzymes III: Kinetics
1:40
Rate of an Enzyme-Catalyzed Reaction & Substrate Concentration
1:41
Graph: Substrate Concentration vs. Reaction Rate
10:43
Rate At Low and High Substrate Concentration
14:26
Michaelis & Menten Kinetics
20:16
More On Rate & Concentration of Substrate
22:46
Steady-State Assumption
26:02
Rate is Determined by How Fast ES Breaks Down to Product
31:36
Total Enzyme Concentration: [Et] = [E] + [ES]
35:35
Rate of ES Formation
36:44
Rate of ES Breakdown
38:40
Measuring Concentration of Enzyme-Substrate Complex
41:19
Measuring Initial & Maximum Velocity
43:43
Michaelis & Menten Equation
46:44
What Happens When V₀ = (1/2) Vmax?
49:12
When [S] << Km
53:32
When [S] >> Km
54:44
Enzymes IV: Lineweaver-Burk Plots

20m 37s

Intro
0:00
Enzymes IV: Lineweaver-Burk Plots
0:45
Deriving The Lineweaver-Burk Equation
0:46
Lineweaver-Burk Plots
3:55
Example 1: Carboxypeptidase A
8:00
More on Km, Vmax, and Enzyme-catalyzed Reaction
15:54
Enzymes V: Enzyme Inhibition

51m 37s

Intro
0:00
Enzymes V: Enzyme Inhibition Overview
0:42
Enzyme Inhibitors Overview
0:43
Classes of Inhibitors
2:32
Competitive Inhibition
3:08
Competitive Inhibition
3:09
Michaelis & Menten Equation in the Presence of a Competitive Inhibitor
7:40
Double-Reciprocal Version of the Michaelis & Menten Equation
14:48
Competitive Inhibition Graph
16:37
Uncompetitive Inhibition
19:23
Uncompetitive Inhibitor
19:24
Michaelis & Menten Equation for Uncompetitive Inhibition
22:10
The Lineweaver-Burk Equation for Uncompetitive Inhibition
26:04
Uncompetitive Inhibition Graph
27:42
Mixed Inhibition
30:30
Mixed Inhibitor
30:31
Double-Reciprocal Version of the Equation
33:34
The Lineweaver-Burk Plots for Mixed Inhibition
35:02
Summary of Reversible Inhibitor Behavior
38:00
Summary of Reversible Inhibitor Behavior
38:01
Note: Non-Competitive Inhibition
42:22
Irreversible Inhibition
45:15
Irreversible Inhibition
45:16
Penicillin & Transpeptidase Enzyme
46:50
Enzymes VI: Regulatory Enzymes

51m 23s

Intro
0:00
Enzymes VI: Regulatory Enzymes
0:45
Regulatory Enzymes Overview
0:46
Example: Glycolysis
2:27
Allosteric Regulatory Enzyme
9:19
Covalent Modification
13:08
Two Other Regulatory Processes
16:28
Allosteric Regulation
20:58
Feedback Inhibition
25:12
Feedback Inhibition Example: L-Threonine → L-Isoleucine
26:03
Covalent Modification
27:26
Covalent Modulators: -PO₃²⁻
29:30
Protein Kinases
31:59
Protein Phosphatases
32:47
Addition/Removal of -PO₃²⁻ and the Effect on Regulatory Enzyme
33:36
Phosphorylation Sites of a Regulatory Enzyme
38:38
Proteolytic Cleavage
41:48
Zymogens: Chymotrypsin & Trypsin
43:58
Enzymes That Use More Than One Regulatory Process: Bacterial Glutamine Synthetase
48:59
Why The Complexity?
50:27
Enzymes VII: Km & Kcat

54m 49s

Intro
0:00
Km
1:48
Recall the Michaelis–Menten Equation
1:49
Km & Enzyme's Affinity
6:18
Rate Forward, Rate Backward, and Equilibrium Constant
11:08
When an Enzyme's Affinity for Its Substrate is High
14:17
More on Km & Enzyme Affinity
17:29
The Measure of Km Under Michaelis–Menten kinetic
23:19
Kcat (First-order Rate Constant or Catalytic Rate Constant)
24:10
Kcat: Definition
24:11
Kcat & The Michaelis–Menten Postulate
25:18
Finding Vmax and [Et}
27:27
Units for Vmax and Kcat
28:26
Kcat: Turnover Number
28:55
Michaelis–Menten Equation
32:12
Km & Kcat
36:37
Second Order Rate Equation
36:38
(Kcat)/(Km): Overview
39:22
High (Kcat)/(Km)
40:20
Low (Kcat)/(Km)
43:16
Practical Big Picture
46:28
Upper Limit to (Kcat)/(Km)
48:56
More On Kcat and Km
49:26
VI. Carbohydrates
Monosaccharides

1h 17m 46s

Intro
0:00
Monosaccharides
1:49
Carbohydrates Overview
1:50
Three Major Classes of Carbohydrates
4:48
Definition of Monosaccharides
5:46
Examples of Monosaccharides: Aldoses
7:06
D-Glyceraldehyde
7:39
D-Erythrose
9:00
D-Ribose
10:10
D-Glucose
11:20
Observation: Aldehyde Group
11:54
Observation: Carbonyl 'C'
12:30
Observation: D & L Naming System
12:54
Examples of Monosaccharides: Ketose
16:54
Dihydroxy Acetone
17:28
D-Erythrulose
18:30
D-Ribulose
19:49
D-Fructose
21:10
D-Glucose Comparison
23:18
More information of Ketoses
24:50
Let's Look Closer at D-Glucoses
25:50
Let's Look At All the D-Hexose Stereoisomers
31:22
D-Allose
32:20
D-Altrose
33:01
D-Glucose
33:39
D-Gulose
35:00
D-Mannose
35:40
D-Idose
36:42
D-Galactose
37:14
D-Talose
37:42
Epimer
40:05
Definition of Epimer
40:06
Example of Epimer: D-Glucose, D-Mannose, and D-Galactose
40:57
Hemiacetal or Hemiketal
44:36
Hemiacetal/Hemiketal Overview
45:00
Ring Formation of the α and β Configurations of D-Glucose
50:52
Ring Formation of the α and β Configurations of Fructose
1:01:39
Haworth Projection
1:07:34
Pyranose & Furanose Overview
1:07:38
Haworth Projection: Pyranoses
1:09:30
Haworth Projection: Furanose
1:14:56
Hexose Derivatives & Reducing Sugars

37m 6s

Intro
0:00
Hexose Derivatives
0:15
Point of Clarification: Forming a Cyclic Sugar From a Linear Sugar
0:16
Let's Recall the α and β Anomers of Glucose
8:42
α-Glucose
10:54
Hexose Derivatives that Play Key Roles in Physiology Progression
17:38
β-Glucose
18:24
β-Glucosamine
18:48
N-Acetyl-β-Glucosamine
20:14
β-Glucose-6-Phosphate
22:22
D-Gluconate
24:10
Glucono-δ-Lactone
26:33
Reducing Sugars
29:50
Reducing Sugars Overview
29:51
Reducing Sugars Example: β-Galactose
32:36
Disaccharides

43m 32s

Intro
0:00
Disaccharides
0:15
Disaccharides Overview
0:19
Examples of Disaccharides & How to Name Them
2:49
Disaccharides Trehalose Overview
15:46
Disaccharides Trehalose: Flip
20:52
Disaccharides Trehalose: Spin
28:36
Example: Draw the Structure
33:12
Polysaccharides

39m 25s

Intro
0:00
Recap Example: Draw the Structure of Gal(α1↔β1)Man
0:38
Polysaccharides
9:46
Polysaccharides Overview
9:50
Homopolysaccharide
13:12
Heteropolysaccharide
13:47
Homopolysaccharide as Fuel Storage
16:23
Starch Has Two Types of Glucose Polymer: Amylose
17:10
Starch Has Two Types of Glucose Polymer: Amylopectin
18:04
Polysaccharides: Reducing End & Non-Reducing End
19:30
Glycogen
20:06
Examples: Structures of Polysaccharides
21:42
Let's Draw an (α1→4) & (α1→6) of Amylopectin by Hand.
28:14
More on Glycogen
31:17
Glycogen, Concentration, & The Concept of Osmolarity
35:16
Polysaccharides, Part 2

44m 15s

Intro
0:00
Polysaccharides
0:17
Example: Cellulose
0:34
Glycoside Bond
7:25
Example Illustrations
12:30
Glycosaminoglycans Part 1
15:55
Glycosaminoglycans Part 2
18:34
Glycosaminoglycans & Sulfate Attachments
22:42
β-D-N-Acetylglucosamine
24:49
β-D-N-AcetylGalactosamine
25:42
β-D-Glucuronate
26:44
β-L-Iduronate
27:54
More on Sulfate Attachments
29:49
Hylarunic Acid
32:00
Hyaluronates
39:32
Other Glycosaminoglycans
40:46
Glycoconjugates

44m 23s

Intro
0:00
Glycoconjugates
0:24
Overview
0:25
Proteoglycan
2:53
Glycoprotein
5:20
Glycolipid
7:25
Proteoglycan vs. Glycoprotein
8:15
Cell Surface Diagram
11:17
Proteoglycan Common Structure
14:24
Example: Chondroitin-4-Sulfate
15:06
Glycoproteins
19:50
The Monomers that Commonly Show Up in The Oligo Portions of Glycoproteins
28:02
N-Acetylneuraminic Acid
31:17
L-Furose
32:37
Example of an N-Linked Oligosaccharide
33:21
Cell Membrane Structure
36:35
Glycolipids & Lipopolysaccharide
37:22
Structure Example
41:28
More Example Problems with Carbohydrates

40m 22s

Intro
0:00
Example 1
1:09
Example 2
2:34
Example 3
5:12
Example 4
16:19
Question
16:20
Solution
17:25
Example 5
24:18
Question
24:19
Structure of 2,3-Di-O-Methylglucose
26:47
Part A
28:11
Part B
33:46
VII. Lipids
Fatty Acids & Triacylglycerols

54m 55s

Intro
0:00
Fatty Acids
0:32
Lipids Overview
0:34
Introduction to Fatty Acid
3:18
Saturated Fatty Acid
6:13
Unsaturated or Polyunsaturated Fatty Acid
7:07
Saturated Fatty Acid Example
7:46
Unsaturated Fatty Acid Example
9:06
Notation Example: Chain Length, Degree of Unsaturation, & Double Bonds Location of Fatty Acid
11:56
Example 1: Draw the Structure
16:18
Example 2: Give the Shorthand for cis,cis-5,8-Hexadecadienoic Acid
20:12
Example 3
23:12
Solubility of Fatty Acids
25:45
Melting Points of Fatty Acids
29:40
Triacylglycerols
34:13
Definition of Triacylglycerols
34:14
Structure of Triacylglycerols
35:08
Example: Triacylglycerols
40:23
Recall Ester Formation
43:57
The Body's Primary Fuel-Reserves
47:22
Two Primary Advantages to Storing Energy as Triacylglycerols Instead of Glycogen: Number 1
49:24
Two Primary Advantages to Storing Energy as Triacylglycerols Instead of Glycogen: Number 2
51:54
Membrane Lipids

38m 51s

Intro
0:00
Membrane Lipids
0:26
Definition of Membrane Lipids
0:27
Five Major Classes of Membrane Lipids
2:38
Glycerophospholipids
5:04
Glycerophospholipids Overview
5:05
The X Group
8:05
Example: Phosphatidyl Ethanolamine
10:51
Example: Phosphatidyl Choline
13:34
Phosphatidyl Serine
15:16
Head Groups
16:50
Ether Linkages Instead of Ester Linkages
20:05
Galactolipids
23:39
Galactolipids Overview
23:40
Monogalactosyldiacylglycerol: MGDG
25:17
Digalactosyldiacylglycerol: DGDG
28:13
Structure Examples 1: Lipid Bilayer
31:35
Structure Examples 2: Cross Section of a Cell
34:56
Structure Examples 3: MGDG & DGDG
36:28
Membrane Lipids, Part 2

38m 20s

Intro
0:00
Sphingolipids
0:11
Sphingolipid Overview
0:12
Sphingosine Structure
1:42
Ceramide
3:56
Subclasses of Sphingolipids Overview
6:00
Subclasses of Sphingolipids: Sphingomyelins
7:53
Sphingomyelins
7:54
Subclasses of Sphingolipids: Glycosphingolipid
12:47
Glycosphingolipid Overview
12:48
Cerebrosides & Globosides Overview
14:33
Example: Cerebrosides
15:43
Example: Globosides
17:14
Subclasses of Sphingolipids: Gangliosides
19:07
Gangliosides
19:08
Medical Application: Tay-Sachs Disease
23:34
Sterols
30:45
Sterols: Basic Structure
30:46
Important Example: Cholesterol
32:01
Structures Example
34:13
The Biologically Active Lipids

48m 36s

Intro
0:00
The Biologically Active Lipids
0:44
Phosphatidyl Inositol Structure
0:45
Phosphatidyl Inositol Reaction
3:24
Image Example
12:49
Eicosanoids
14:12
Arachidonic Acid & Membrane Lipid Containing Arachidonic Acid
18:41
Three Classes of Eicosanoids
20:42
Overall Structures
21:38
Prostagladins
22:56
Thromboxane
27:19
Leukotrienes
30:19
More On The Biologically Active Lipids
33:34
Steroid Hormones
33:35
Fat Soluble Vitamins
38:25
Vitamin D₃
40:40
Vitamin A
43:17
Vitamin E
45:12
Vitamin K
47:17
VIII. Energy & Biological Systems (Bioenergetics)
Thermodynamics, Free Energy & Equilibrium

45m 51s

Intro
0:00
Thermodynamics, Free Energy and Equilibrium
1:03
Reaction: Glucose + Pi → Glucose 6-Phosphate
1:50
Thermodynamics & Spontaneous Processes
3:31
In Going From Reactants → Product, a Reaction Wants to Release Heat
6:30
A Reaction Wants to Become More Disordered
9:10
∆H < 0
10:30
∆H > 0
10:57
∆S > 0
11:23
∆S <0
11:56
∆G = ∆H - T∆S at Constant Pressure
12:15
Gibbs Free Energy
15:00
∆G < 0
16:49
∆G > 0
17:07
Reference Frame For Thermodynamics Measurements
17:57
More On BioChemistry Standard
22:36
Spontaneity
25:36
Keq
31:45
Example: Glucose + Pi → Glucose 6-Phosphate
34:14
Example Problem 1
40:25
Question
40:26
Solution
41:12
More on Thermodynamics & Free Energy

37m 6s

Intro
0:00
More on Thermodynamics & Free Energy
0:16
Calculating ∆G Under Standard Conditions
0:17
Calculating ∆G Under Physiological Conditions
2:05
∆G < 0
5:39
∆G = 0
7:03
Reaction Moving Forward Spontaneously
8:00
∆G & The Maximum Theoretical Amount of Free Energy Available
10:36
Example Problem 1
13:11
Reactions That Have Species in Common
17:48
Example Problem 2: Part 1
20:10
Example Problem 2: Part 2- Enzyme Hexokinase & Coupling
25:08
Example Problem 2: Part 3
30:34
Recap
34:45
ATP & Other High-Energy Compounds

44m 32s

Intro
0:00
ATP & Other High-Energy Compounds
0:10
Endergonic Reaction Coupled With Exergonic Reaction
0:11
Major Theme In Metabolism
6:56
Why the ∆G°' for ATP Hydrolysis is Large & Negative
12:24
∆G°' for ATP Hydrolysis
12:25
Reason 1: Electrostatic Repulsion
14:24
Reason 2: Pi & Resonance Forms
15:33
Reason 3: Concentrations of ADP & Pi
17:32
ATP & Other High-Energy Compounds Cont'd
18:48
More On ∆G°' & Hydrolysis
18:49
Other Compounds That Have Large Negative ∆G°' of Hydrolysis: Phosphoenol Pyruvate (PEP)
25:14
Enzyme Pyruvate Kinase
30:36
Another High Energy Molecule: 1,3 Biphosphoglycerate
36:17
Another High Energy Molecule: Phophocreatine
39:41
Phosphoryl Group Transfers

30m 8s

Intro
0:00
Phosphoryl Group Transfer
0:27
Phosphoryl Group Transfer Overview
0:28
Example: Glutamate → Glutamine Part 1
7:11
Example: Glutamate → Glutamine Part 2
13:29
ATP Not Only Transfers Phosphoryl, But Also Pyrophosphoryl & Adenylyl Groups
17:03
Attack At The γ Phosphorous Transfers a Phosphoryl
19:02
Attack At The β Phosphorous Gives Pyrophosphoryl
22:44
Oxidation-Reduction Reactions

49m 46s

Intro
0:00
Oxidation-Reduction Reactions
1:32
Redox Reactions
1:33
Example 1: Mg + Al³⁺ → Mg²⁺ + Al
3:49
Reduction Potential Definition
10:47
Reduction Potential Example
13:38
Organic Example
22:23
Review: How To Find The Oxidation States For Carbon
24:15
Examples: Oxidation States For Carbon
27:45
Example 1: Oxidation States For Carbon
27:46
Example 2: Oxidation States For Carbon
28:36
Example 3: Oxidation States For Carbon
29:18
Example 4: Oxidation States For Carbon
29:44
Example 5: Oxidation States For Carbon
30:10
Example 6: Oxidation States For Carbon
30:40
Example 7: Oxidation States For Carbon
31:20
Example 8: Oxidation States For Carbon
32:10
Example 9: Oxidation States For Carbon
32:52
Oxidation-Reduction Reactions, cont'd
35:22
More On Reduction Potential
35:28
Lets' Start With ∆G = ∆G°' + RTlnQ
38:29
Example: Oxidation Reduction Reactions
41:42
More On Oxidation-Reduction Reactions

56m 34s

Intro
0:00
More On Oxidation-Reduction Reactions
0:10
Example 1: What If the Concentrations Are Not Standard?
0:11
Alternate Procedure That Uses The 1/2 Reactions Individually
8:57
Universal Electron Carriers in Aqueous Medium: NAD+ & NADH
15:12
The Others Are…
19:22
NAD+ & NADP Coenzymes
20:56
FMN & FAD
22:03
Nicotinamide Adenine Dinucleotide (Phosphate)
23:03
Reduction 1/2 Reactions
36:10
Ratio of NAD+ : NADH
36:52
Ratio of NADPH : NADP+
38:02
Specialized Roles of NAD+ & NADPH
38:48
Oxidoreductase Enzyme Overview
40:26
Examples of Oxidoreductase
43:32
The Flavin Nucleotides
46:46
Example Problems For Bioenergetics

42m 12s

Intro
0:00
Example 1: Calculate the ∆G°' For The Following Reaction
1:04
Example 1: Question
1:05
Example 1: Solution
2:20
Example 2: Calculate the Keq For the Following
4:20
Example 2: Question
4:21
Example 2: Solution
5:54
Example 3: Calculate the ∆G°' For The Hydrolysis of ATP At 25°C
8:52
Example 3: Question
8:53
Example 3: Solution
10:30
Example 3: Alternate Procedure
13:48
Example 4: Problems For Bioenergetics
16:46
Example 4: Questions
16:47
Example 4: Part A Solution
21:19
Example 4: Part B Solution
23:26
Example 4: Part C Solution
26:12
Example 5: Problems For Bioenergetics
29:27
Example 5: Questions
29:35
Example 5: Solution - Part 1
32:16
Example 5: Solution - Part 2
34:39
IX. Glycolysis and Gluconeogenesis
Overview of Glycolysis I

43m 32s

Intro
0:00
Overview of Glycolysis
0:48
Three Primary Paths For Glucose
1:04
Preparatory Phase of Glycolysis
4:40
Payoff Phase of Glycolysis
6:40
Glycolysis Reactions Diagram
7:58
Enzymes of Glycolysis
12:41
Glycolysis Reactions
16:02
Step 1
16:03
Step 2
18:03
Step 3
18:52
Step 4
20:08
Step 5
21:42
Step 6
22:44
Step 7
24:22
Step 8
25:11
Step 9
26:00
Step 10
26:51
Overview of Glycolysis Cont.
27:28
The Overall Reaction for Glycolysis
27:29
Recall The High-Energy Phosphorylated Compounds Discusses In The Bioenergetics Unit
33:10
What Happens To The Pyruvate That Is Formed?
37:58
Glycolysis II

1h 1m 47s

Intro
0:00
Glycolysis Step 1: The Phosphorylation of Glucose
0:27
Glycolysis Step 1: Reaction
0:28
Hexokinase
2:28
Glycolysis Step 1: Mechanism-Simple Nucleophilic Substitution
6:34
Glycolysis Step 2: Conversion of Glucose 6-Phosphate → Fructose 6-Phosphate
11:33
Glycolysis Step 2: Reaction
11:34
Glycolysis Step 2: Mechanism, Part 1
14:40
Glycolysis Step 2: Mechanism, Part 2
18:16
Glycolysis Step 2: Mechanism, Part 3
19:56
Glycolysis Step 2: Mechanism, Part 4 (Ring Closing & Dissociation)
21:54
Glycolysis Step 3: Conversion of Fructose 6-Phosphate to Fructose 1,6-Biphosphate
24:16
Glycolysis Step 3: Reaction
24:17
Glycolysis Step 3: Mechanism
26:40
Glycolysis Step 4: Cleavage of Fructose 1,6-Biphosphate
31:10
Glycolysis Step 4: Reaction
31:11
Glycolysis Step 4: Mechanism, Part 1 (Binding & Ring Opening)
35:26
Glycolysis Step 4: Mechanism, Part 2
37:40
Glycolysis Step 4: Mechanism, Part 3
39:30
Glycolysis Step 4: Mechanism, Part 4
44:00
Glycolysis Step 4: Mechanism, Part 5
46:34
Glycolysis Step 4: Mechanism, Part 6
49:00
Glycolysis Step 4: Mechanism, Part 7
50:12
Hydrolysis of The Imine
52:33
Glycolysis Step 5: Conversion of Dihydroxyaceton Phosphate to Glyceraldehyde 3-Phosphate
55:38
Glycolysis Step 5: Reaction
55:39
Breakdown and Numbering of Sugar
57:40
Glycolysis III

59m 17s

Intro
0:00
Glycolysis Step 5: Conversion of Dihydroxyaceton Phosphate to Glyceraldehyde 3-Phosphate
0:44
Glycolysis Step 5: Mechanism, Part 1
0:45
Glycolysis Step 5: Mechanism, Part 2
3:53
Glycolysis Step 6: Oxidation of Glyceraldehyde 3-Phosphate to 1,3-Biphosphoglycerate
5:14
Glycolysis Step 6: Reaction
5:15
Glycolysis Step 6: Mechanism, Part 1
8:52
Glycolysis Step 6: Mechanism, Part 2
12:58
Glycolysis Step 6: Mechanism, Part 3
14:26
Glycolysis Step 6: Mechanism, Part 4
16:23
Glycolysis Step 7: Phosphoryl Transfer From 1,3-Biphosphoglycerate to ADP to Form ATP
19:08
Glycolysis Step 7: Reaction
19:09
Substrate-Level Phosphorylation
23:18
Glycolysis Step 7: Mechanism (Nucleophilic Substitution)
26:57
Glycolysis Step 8: Conversion of 3-Phosphoglycerate to 2-Phosphoglycerate
28:44
Glycolysis Step 8: Reaction
28:45
Glycolysis Step 8: Mechanism, Part 1
30:08
Glycolysis Step 8: Mechanism, Part 2
32:24
Glycolysis Step 8: Mechanism, Part 3
34:02
Catalytic Cycle
35:42
Glycolysis Step 9: Dehydration of 2-Phosphoglycerate to Phosphoenol Pyruvate
37:20
Glycolysis Step 9: Reaction
37:21
Glycolysis Step 9: Mechanism, Part 1
40:12
Glycolysis Step 9: Mechanism, Part 2
42:01
Glycolysis Step 9: Mechanism, Part 3
43:58
Glycolysis Step 10: Transfer of a Phosphoryl Group From Phosphoenol Pyruvate To ADP To Form ATP
45:16
Glycolysis Step 10: Reaction
45:17
Substrate-Level Phosphorylation
48:32
Energy Coupling Reaction
51:24
Glycolysis Balance Sheet
54:15
Glycolysis Balance Sheet
54:16
What Happens to The 6 Carbons of Glucose?
56:22
What Happens to 2 ADP & 2 Pi?
57:04
What Happens to The 4e⁻ ?
57:15
Glycolysis IV

39m 47s

Intro
0:00
Feeder Pathways
0:42
Feeder Pathways Overview
0:43
Starch, Glycogen
2:25
Lactose
4:38
Galactose
4:58
Manose
5:22
Trehalose
5:45
Sucrose
5:56
Fructose
6:07
Fates of Pyruvate: Aerobic & Anaerobic Conditions
7:39
Aerobic Conditions & Pyruvate
7:40
Anaerobic Fates of Pyruvate
11:18
Fates of Pyruvate: Lactate Acid Fermentation
14:10
Lactate Acid Fermentation
14:11
Fates of Pyruvate: Ethanol Fermentation
19:01
Ethanol Fermentation Reaction
19:02
TPP: Thiamine Pyrophosphate (Functions and Structure)
23:10
Ethanol Fermentation Mechanism, Part 1
27:53
Ethanol Fermentation Mechanism, Part 2
29:06
Ethanol Fermentation Mechanism, Part 3
31:15
Ethanol Fermentation Mechanism, Part 4
32:44
Ethanol Fermentation Mechanism, Part 5
34:33
Ethanol Fermentation Mechanism, Part 6
35:48
Gluconeogenesis I

41m 34s

Intro
0:00
Gluconeogenesis, Part 1
1:02
Gluconeogenesis Overview
1:03
3 Glycolytic Reactions That Are Irreversible Under Physiological Conditions
2:29
Gluconeogenesis Reactions Overview
6:17
Reaction: Pyruvate to Oxaloacetate
11:07
Reaction: Oxaloacetate to Phosphoenolpyruvate (PEP)
13:29
First Pathway That Pyruvate Can Take to Become Phosphoenolpyruvate
15:24
Second Pathway That Pyruvate Can Take to Become Phosphoenolpyruvate
21:00
Transportation of Pyruvate From The Cytosol to The Mitochondria
24:15
Transportation Mechanism, Part 1
26:41
Transportation Mechanism, Part 2
30:43
Transportation Mechanism, Part 3
34:04
Transportation Mechanism, Part 4
38:14
Gluconeogenesis II

34m 18s

Intro
0:00
Oxaloacetate → Phosphoenolpyruvate (PEP)
0:35
Mitochondrial Membrane Does Not Have a Transporter for Oxaloactate
0:36
Reaction: Oxaloacetate to Phosphoenolpyruvate (PEP)
3:36
Mechanism: Oxaloacetate to Phosphoenolpyruvate (PEP)
4:48
Overall Reaction: Pyruvate to Phosphoenolpyruvate
7:01
Recall The Two Pathways That Pyruvate Can Take to Become Phosphoenolpyruvate
10:16
NADH in Gluconeogenesis
12:29
Second Pathway: Lactate → Pyruvate
18:22
Cytosolic PEP Carboxykinase, Mitochondrial PEP Carboxykinase, & Isozymes
18:23
2nd Bypass Reaction
23:04
3rd Bypass Reaction
24:01
Overall Process
25:17
Other Feeder Pathways For Gluconeogenesis
26:35
Carbon Intermediates of The Citric Acid Cycle
26:36
Amino Acids & The Gluconeogenic Pathway
29:45
Glycolysis & Gluconeogenesis Are Reciprocally Regulated
32:00
The Pentose Phosphate Pathway

42m 52s

Intro
0:00
The Pentose Phosphate Pathway Overview
0:17
The Major Fate of Glucose-6-Phosphate
0:18
The Pentose Phosphate Pathway (PPP) Overview
1:00
Oxidative Phase of The Pentose Phosphate Pathway
4:33
Oxidative Phase of The Pentose Phosphate Pathway: Reaction Overview
4:34
Ribose-5-Phosphate: Glutathione & Reductive Biosynthesis
9:02
Glucose-6-Phosphate to 6-Phosphogluconate
12:48
6-Phosphogluconate to Ribulose-5-Phosphate
15:39
Ribulose-5-Phosphate to Ribose-5-Phosphate
17:05
Non-Oxidative Phase of The Pentose Phosphate Pathway
19:55
Non-Oxidative Phase of The Pentose Phosphate Pathway: Overview
19:56
General Transketolase Reaction
29:03
Transaldolase Reaction
35:10
Final Transketolase Reaction
39:10
X. The Citric Acid Cycle (Krebs Cycle)
Citric Acid Cycle I

36m 10s

Intro
0:00
Stages of Cellular Respiration
0:23
Stages of Cellular Respiration
0:24
From Pyruvate to Acetyl-CoA
6:56
From Pyruvate to Acetyl-CoA: Pyruvate Dehydrogenase Complex
6:57
Overall Reaction
8:42
Oxidative Decarboxylation
11:54
Pyruvate Dehydrogenase (PDH) & Enzymes
15:30
Pyruvate Dehydrogenase (PDH) Requires 5 Coenzymes
17:15
Molecule of CoEnzyme A
18:52
Thioesters
20:56
Lipoic Acid
22:31
Lipoate Is Attached To a Lysine Residue On E₂
24:42
Pyruvate Dehydrogenase Complex: Reactions
26:36
E1: Reaction 1 & 2
30:38
E2: Reaction 3
31:58
E3: Reaction 4 & 5
32:44
Substrate Channeling
34:17
Citric Acid Cycle II

49m 20s

Intro
0:00
Citric Acid Cycle Reactions Overview
0:26
Citric Acid Cycle Reactions Overview: Part 1
0:27
Citric Acid Cycle Reactions Overview: Part 2
7:03
Things to Note
10:58
Citric Acid Cycle Reactions & Mechanism
13:57
Reaction 1: Formation of Citrate
13:58
Reaction 1: Mechanism
19:01
Reaction 2: Citrate to Cis Aconistate to Isocitrate
28:50
Reaction 3: Isocitrate to α-Ketoglutarate
32:35
Reaction 3: Two Isocitrate Dehydrogenase Enzymes
36:24
Reaction 3: Mechanism
37:33
Reaction 4: Oxidation of α-Ketoglutarate to Succinyl-CoA
41:38
Reaction 4: Notes
46:34
Citric Acid Cycle III

44m 11s

Intro
0:00
Citric Acid Cycle Reactions & Mechanism
0:21
Reaction 5: Succinyl-CoA to Succinate
0:24
Reaction 5: Reaction Sequence
2:35
Reaction 6: Oxidation of Succinate to Fumarate
8:28
Reaction 7: Fumarate to Malate
10:17
Reaction 8: Oxidation of L-Malate to Oxaloacetate
14:15
More On The Citric Acid Cycle
17:17
Energy from Oxidation
17:18
How Can We Transfer This NADH Into the Mitochondria
27:10
Citric Cycle is Amphibolic - Works In Both Anabolic & Catabolic Pathways
32:06
Biosynthetic Processes
34:29
Anaplerotic Reactions Overview
37:26
Anaplerotic: Reaction 1
41:42
XI. Catabolism of Fatty Acids
Fatty Acid Catabolism I

48m 11s

Intro
0:00
Introduction to Fatty Acid Catabolism
0:21
Introduction to Fatty Acid Catabolism
0:22
Vertebrate Cells Obtain Fatty Acids for Catabolism From 3 Sources
2:16
Diet: Part 1
4:00
Diet: Part 2
5:35
Diet: Part 3
6:20
Diet: Part 4
6:47
Diet: Part 5
10:18
Diet: Part 6
10:54
Diet: Part 7
12:04
Diet: Part 8
12:26
Fats Stored in Adipocytes Overview
13:54
Fats Stored in Adipocytes (Fat Cells): Part 1
16:13
Fats Stored in Adipocytes (Fat Cells): Part 2
17:16
Fats Stored in Adipocytes (Fat Cells): Part 3
19:42
Fats Stored in Adipocytes (Fat Cells): Part 4
20:52
Fats Stored in Adipocytes (Fat Cells): Part 5
22:56
Mobilization of TAGs Stored in Fat Cells
24:35
Fatty Acid Oxidation
28:29
Fatty Acid Oxidation
28:48
3 Reactions of the Carnitine Shuttle
30:42
Carnitine Shuttle & The Mitochondrial Matrix
36:25
CAT I
43:58
Carnitine Shuttle is the Rate-Limiting Steps
46:24
Fatty Acid Catabolism II

45m 58s

Intro
0:00
Fatty Acid Catabolism
0:15
Fatty Acid Oxidation Takes Place in 3 Stages
0:16
β-Oxidation
2:05
β-Oxidation Overview
2:06
Reaction 1
4:20
Reaction 2
7:35
Reaction 3
8:52
Reaction 4
10:16
β-Oxidation Reactions Discussion
11:34
Notes On β-Oxidation
15:14
Double Bond After The First Reaction
15:15
Reaction 1 is Catalyzed by 3 Isozymes of Acyl-CoA Dehydrogenase
16:04
Reaction 2 & The Addition of H₂O
18:38
After Reaction 4
19:24
Production of ATP
20:04
β-Oxidation of Unsaturated Fatty Acid
21:25
β-Oxidation of Unsaturated Fatty Acid
22:36
β-Oxidation of Mono-Unsaturates
24:49
β-Oxidation of Mono-Unsaturates: Reaction 1
24:50
β-Oxidation of Mono-Unsaturates: Reaction 2
28:43
β-Oxidation of Mono-Unsaturates: Reaction 3
30:50
β-Oxidation of Mono-Unsaturates: Reaction 4
31:06
β-Oxidation of Polyunsaturates
32:29
β-Oxidation of Polyunsaturates: Part 1
32:30
β-Oxidation of Polyunsaturates: Part 2
37:08
β-Oxidation of Polyunsaturates: Part 3
40:25
Fatty Acid Catabolism III

33m 18s

Intro
0:00
Fatty Acid Catabolism
0:43
Oxidation of Fatty Acids With an Odd Number of Carbons
0:44
β-oxidation in the Mitochondrion & Two Other Pathways
9:08
ω-oxidation
10:37
α-oxidation
17:22
Ketone Bodies
19:08
Two Fates of Acetyl-CoA Formed by β-Oxidation Overview
19:09
Ketone Bodies: Acetone
20:42
Ketone Bodies: Acetoacetate
20:57
Ketone Bodies: D-β-hydroxybutyrate
21:25
Two Fates of Acetyl-CoA Formed by β-Oxidation: Part 1
22:05
Two Fates of Acetyl-CoA Formed by β-Oxidation: Part 2
26:59
Two Fates of Acetyl-CoA Formed by β-Oxidation: Part 3
30:52
XII. Catabolism of Amino Acids and the Urea Cycle
Overview & The Aminotransferase Reaction

40m 59s

Intro
0:00
Overview of The Aminotransferase Reaction
0:25
Overview of The Aminotransferase Reaction
0:26
The Aminotransferase Reaction: Process 1
3:06
The Aminotransferase Reaction: Process 2
6:46
Alanine From Muscle Tissue
10:54
Bigger Picture of the Aminotransferase Reaction
14:52
Looking Closely at Process 1
19:04
Pyridoxal Phosphate (PLP)
24:32
Pyridoxamine Phosphate
25:29
Pyridoxine (B6)
26:38
The Function of PLP
27:12
Mechanism Examples
28:46
Reverse Reaction: Glutamate to α-Ketoglutarate
35:34
Glutamine & Alanine: The Urea Cycle I

39m 18s

Intro
0:00
Glutamine & Alanine: The Urea Cycle I
0:45
Excess Ammonia, Glutamate, and Glutamine
0:46
Glucose-Alanine Cycle
9:54
Introduction to the Urea Cycle
20:56
The Urea Cycle: Production of the Carbamoyl Phosphate
22:59
The Urea Cycle: Reaction & Mechanism Involving the Carbamoyl Phosphate Synthetase
33:36
Glutamine & Alanine: The Urea Cycle II

36m 21s

Intro
0:00
Glutamine & Alanine: The Urea Cycle II
0:14
The Urea Cycle Overview
0:34
Reaction 1: Ornithine → Citrulline
7:30
Reaction 2: Citrulline → Citrullyl-AMP
11:15
Reaction 2': Citrullyl-AMP → Argininosuccinate
15:25
Reaction 3: Argininosuccinate → Arginine
20:42
Reaction 4: Arginine → Orthinine
24:00
Links Between the Citric Acid Cycle & the Urea Cycle
27:47
Aspartate-argininosuccinate Shunt
32:36
Amino Acid Catabolism

47m 58s

Intro
0:00
Amino Acid Catabolism
0:10
Common Amino Acids and 6 Major Products
0:11
Ketogenic Amino Acid
1:52
Glucogenic Amino Acid
2:51
Amino Acid Catabolism Diagram
4:18
Cofactors That Play a Role in Amino Acid Catabolism
7:00
Biotin
8:42
Tetrahydrofolate
10:44
S-Adenosylmethionine (AdoMet)
12:46
Tetrahydrobiopterin
13:53
S-Adenosylmethionine & Tetrahydrobiopterin Molecules
14:41
Catabolism of Phenylalanine
18:30
Reaction 1: Phenylalanine to Tyrosine
18:31
Reaction 2: Tyrosine to p-Hydroxyphenylpyruvate
21:36
Reaction 3: p-Hydroxyphenylpyruvate to Homogentisate
23:50
Reaction 4: Homogentisate to Maleylacetoacetate
25:42
Reaction 5: Maleylacetoacetate to Fumarylacetoacetate
28:20
Reaction 6: Fumarylacetoacetate to Fumarate & Succinyl-CoA
29:51
Reaction 7: Fate of Fumarate & Succinyl-CoA
31:14
Phenylalanine Hydroxylase
33:33
The Phenylalanine Hydroxylase Reaction
33:34
Mixed-Function Oxidases
40:26
When Phenylalanine Hydoxylase is Defective: Phenylketonuria (PKU)
44:13
XIII. Oxidative Phosphorylation and ATP Synthesis
Oxidative Phosphorylation I

41m 11s

Intro
0:00
Oxidative Phosphorylation
0:54
Oxidative Phosphorylation Overview
0:55
Mitochondrial Electron Transport Chain Diagram
7:15
Enzyme Complex I of the Electron Transport Chain
12:27
Enzyme Complex II of the Electron Transport Chain
14:02
Enzyme Complex III of the Electron Transport Chain
14:34
Enzyme Complex IV of the Electron Transport Chain
15:30
Complexes Diagram
16:25
Complex I
18:25
Complex I Overview
18:26
What is Ubiquinone or Coenzyme Q?
20:02
Coenzyme Q Transformation
22:37
Complex I Diagram
24:47
Fe-S Proteins
26:42
Transfer of H⁺
29:42
Complex II
31:06
Succinate Dehydrogenase
31:07
Complex II Diagram & Process
32:54
Other Substrates Pass Their e⁻ to Q: Glycerol 3-Phosphate
37:31
Other Substrates Pass Their e⁻ to Q: Fatty Acyl-CoA
39:02
Oxidative Phosphorylation II

36m 27s

Intro
0:00
Complex III
0:19
Complex III Overview
0:20
Complex III: Step 1
1:56
Complex III: Step 2
6:14
Complex IV
8:42
Complex IV: Cytochrome Oxidase
8:43
Oxidative Phosphorylation, cont'd
17:18
Oxidative Phosphorylation: Summary
17:19
Equation 1
19:13
How Exergonic is the Reaction?
21:03
Potential Energy Represented by Transported H⁺
27:24
Free Energy Change for the Production of an Electrochemical Gradient Via an Ion Pump
28:48
Free Energy Change in Active Mitochondria
32:02
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1 answer

Last reply by: Professor Hovasapian
Thu Feb 27, 2014 7:35 PM

Post by Yanet Ortiz on February 26, 2014

Great lecture!!! very clear explanation!!! thank you

Protein Function III: More on Hemoglobin

Lecture Slides are screen-captured images of important points in the lecture. Students can download and print out these lecture slide images to do practice problems as well as take notes while watching the lecture.

  • Intro 0:00
  • Protein Function III: More on Hemoglobin 0:11
    • Two Models for Cooperative Binding: MWC & Sequential Model
    • MWC Model
    • Hemoglobin Subunits
    • Sequential Model
    • Hemoglobin Transports H⁺ & CO₂
    • Binding Sites of H⁺ and CO₂
    • CO₂ is Converted to Bicarbonate
    • Production of H⁺ & CO₂ in Tissues
    • H⁺ & CO₂ Binding are Inversely Related to O₂ Binding
    • The H⁺ Bohr Effect: His¹⁴⁶ Residue on the β Subunits
    • Heterotropic Allosteric Regulation of O₂ Binding by 2,3-Biphosphoglycerate (2,3 BPG)
    • Binding Curve for 2,3 BPG

Transcription: Protein Function III: More on Hemoglobin

Hello and welcome back to Educator.com, and welcome back to Biochemistry.0000

Today, we are going to continue our discussion of hemoglobin and discuss cooperative binding a little bit more.0004

OK, let’s get started.0010

OK, now, as far as the cooperative binding of hemoglobin is concerned, there are 2 models that have been proposed for how this actually happens.0014

Let’s see what we have here.0023

There are 2 models for cooperative binding.0029

And again, cooperative binding just refers to the fact that when one particular ligand attaches to one part of this hemoglobin molecule, it causes certain changes to take place in the conformation - things like that - that makes the binding of the second, third and subsequent ligands either a little easier or a little harder.0039

That is all cooperative binding means; it means it is not just a simple process of bind, unbind, bind, unbind.0059

There is more interaction going on.0066

Two models for cooperative binding, they are called the MWC model, and the MWC just refers to the last names of the men who proposed this and the sequential model, OK, MWC model and sequential model.0070

Now, for the MWC, the basic assumptions of the model is that the subunits of the protein - and again, in our case, the protein that we are interested in is the hemoglobin, so we have the 4 subunits, the 2 alphas and the 2 betas, I will go ahead and write hemoglobin in this case - they function identically - OK - that they exist in 2 conformations; and that all subunits, they transition from one state to the other state simultaneously.0091

Excuse me.0160

OK, in other words, in the case of hemoglobin, everything is either going to be in the T-state, the tensed state, the deoxyhemoglobin state or everything is going to be in the R-state, the relaxed state, the oxyhemoglobin.0181

Remember, the T-state is the one that does not want to bind H2, does not want to bind O2 - I am sorry - not H2.0198

The R-state is the one that does tend to bind O2.0205

Let’s go ahead, and let me go to blue for this one.0214

That is for hemoglobin, Hb, all the subunits are either T or R- one or the other.0220

OK, pictorially this is what it looks like; you are going to get something like this.0239

It is going to take a couple of minutes to draw out this picture here; we have 4 subunits in our hemoglobin molecule.0244

We have 1, 2, 3, 4; I will just do it that way, and then, let’s see.0251

I hope I have enough room here, I should; let me make my...I am sorry.0260

I am going to make my circles a little bit smaller; I would like all of these to be on one page.0262

I am going to go 1, 2, 3, 4, and I will do my equilibrium arrows afterward actually, 2, 3, 4, 1, 2, 3, 4.0266

That is 2, 1, 2, 3, 4; that is 3.0280

1, 2, 3, 4, that is 4, and 1, 2, 3, 4, that is 5.0282

That is going to be our 4 subunits of hemoglobin, 1, 2, 3, 4, the 2 alphas, the 2 betas.0288

This is going to be the T-state; we will circle, we will represent the T-state.0293

Now, I will go ahead and draw the R-state.0298

The R-state is going to be represented as squares; let me go ahead and draw them in, and then, we will talk about the movements between these states.0302

Here we go; this is our T-state over here on the left, and we have our R-state.0315

And again, for the MWC model, they are either all in the T-state or all in the R-state.0319

What you have is a bunch of equilibriums that exist between all of these forms.0325

Let me go ahead and draw in all of my equilibrium arrows, and I will talk about this in just a minute.0331

Just let me make sure to get all these drawn in; I hope I have not forgotten anything here.0345

OK, now, I am going to go ahead and put 1 ligand which is the oxygen.0350

I will go ahead and do this in red; that has 1 ligand attached, and of course, when it makes the transition, this one has 2 ligands attached, and then, in the case of oxygen, the ligand we are talking about is diatomic oxygen, oxygen gas, O2.0354

Let’s go ahead and, now, do a 3 L, L, L, L, L, L, and, of course, our fourth final, of course, has 4.0372

Each of the subunits has an O2 attached; the MWC model, it looks something like this.0385

You start out with, let’s say, 4 empty subunits.0391

It is in equilibrium with the R-state of the 4 empty subunits.0396

From here, either one of these can bind a ligand.0401

If this one binds one ligand, 1 O2 molecule, OK, now, this one might bind another one.0404

It might go this way, the transition from the T-state to the R-state completely.0411

Again, the MWC model says that the transitions take place for all of them simultaneously, all T-state or all R-state.0416

Maybe, it makes the transition over here, and then, maybe, now, in the R-state, it binds another ligand.0425

Well, we know that in the R-state, as more ligands bind, there is more of a transition and the O2 tends to bind easier.0431

Maybe, it does not make the transition back here, or maybe, a few of the enzymes actually do make it back here.0440

They bind the third, and maybe it comes back here; at some point, we go from all empty to all full, and all of these equilibriums exist.0446

It can go this way, this way, this way, this way, this way, this way, this way; they can go this way, this way.0454

That is what all of these equilibrium arrows mean; these are pathways that it can actually follow to get from no binding to every single subunit is completely bound by its ligand, which is oxygen in this case.0460

This is a pictorial model of how the MWC mechanism works.0473

OK, now, in sequential model, I will just say…actually, let me go back to blue here.0479

I like the blue very much.0490

OK, in sequential binding, each individual subunit can be in either state, can be in either T - well, I will just say in either state - and the conformational change in 1 subunit can induce a change in the other or others, can induce a change in another subunit or others.0494

It can be one or more; a change in one subunit can cause, maybe, another subunit to change, or it might cause a second subunit to change, or it might cause all 3 subunits to change, but they are free.0557

Each one is individual; they are not necessarily...they are cooperative in the sense that they affect each other, but they do not all have to be T or all have to be R- either one can be either.0567

OK, induce a change in the other causing the ligand or ligand - again, pronunciation - to bind more tightly.0578

And we know, again, T-state to R-state, as it makes the transition from the T-state to the R-state, the O2 is bound more tightly.0598

OK, now, let’s do a pictorial version of this; the sequential binding, the pictorial version of this has actually a lot of those states.0607

In the previous picture that we saw, there were not too many; this one has quite a few because each individual subunit is free to be in either state.0615

I am going to draw a portion of it that involves change in 2 of the subunits.0624

It actually has more when you have changes in all 4 subunits, but I am only going to do a portion of it; but you should be able to understand what it is that is going on.0630

You should be able to hopefully, you will actually finish off the picture.0639

Let me go ahead and do this in...no, you know what, this time, I think I will do black.0644

Excuse me; I have got 1, 2, 3, 4, 1, 2, 3, 4, 1, 2, 3, 4.0651

OK, this time, I have got 1, 2, 3, and this one is a square.0662

I have got 1, 2, 3; this top right is a square, and I have got 1, 2, 3.0670

This top right is a square.0675

OK, this time, I have circle, circle, square, square or T-state, R-state.0679

The Ts are the circles; the squares are the R: circle, circle, square, square and circle, circle, square, square0685

Alright, now, let’s go ahead and draw in our equilibrium arrows; these are going to be a little bit more complex.0697

It is not going to be just horizontal and vertical; there is actually going to be equilibriums that exist diagonally.0702

Let me go ahead and put the...let’s be nice and systematic; let’s go horizontal first, get those out of the way.0708

Now, let’s go ahead and do the vertical, there - actually I prefer that - and then, this way and that way and this way and that way, this way and that way, this way and that way.0714

And now, we have an equilibrium that exists here also, so equilibriums all over the place.0728

OK, now, let’s go ahead and fill in with the ligand, our oxygen.0736

We can have it in this state where there are all the T-state.0742

We can have the transition of 3 of them can be in the T-state; 1 of them can be in the R-state.0748

Two of them can be in the T-state; 2 of them can be in the R-state, and what I mean by you finishing off, that this is being just a portion of the whole picture, the next column over will be 3 squares and 1 circle, and then the next column will be 4 squares.0750

The same thing down here, it is just a little broader.0764

I am just doing a portion of it here; these can be all empty.0767

They can be all empty; they can be all full.0772

One could be empty, the others full; one could be full, the others empty.0774

Let’s go ahead and draw in some ligands here: L, L, L, now, for 2 ligands bound.0779

OK, and again, it goes a little bit further this way and a little bit further this way.0792

OK, all this means is that at any given time, any subunit can be in any state at any given time with ligand or without.0798

That is what is key here; OK, any subunit can be in any state, and by "any", we mean the 2 states, the T or the R.0808

In the case of hemoglobin, another enzyme another protein might have 5 states.0823

It could be in any of those 5- any state at any time with ligand or without.0829

All kinds of possibilities are available here.0843

You can start here; maybe, you can bind the ligand to the T-state.0848

Maybe, this particular subunit starts to make the transition, itself, from the T-state to the R-state, and now, it has moved over here.0853

Now, maybe, this one decides to bind another ligand, and it binds it over here; and then, maybe this subunit, it bounded in the T-state, but now, it has gone ahead and transitioned to the R-state, or maybe, this one, this particular subunit, when this one binds, it causes a conformational change in this subunit over here on the bottom left.0861

It causes it to transition into the R-state, and then, the R-state actually binds another ligand.0882

We can go here or here; that is what these arrows mean.0888

They are pathways that this particular protein can take to get from one place to another.0892

It does not have to always be in one way; if I wanted to go from here, the top left where everything is in the T-state, and everything is empty, all the way down here where I have 2 of them in the T-state, 2 in the R-state and the ligands happen to be in the R-state subunits, I can go 1, 2, 3, 4.0898

That is 1 path; I can go 1, 2, 3, 4.0918

That is another path; I can go 1, 2, 3, 4, 5, 6, 7, 8, 9.0920

It is an infinite number of pathways.0926

What this model represents is pictorially, it gives you an idea of the complexity of the interactions of cooperative binding.0928

It is not a simple thing; we can describe it, but the idea is to understand that this is very, very complex and very, very subtle.0937

This gives you an idea of just how complex and how subtle.0947

Pathways, double arrow, if the arrows were in one direction, it would actually minimize the pathways, but it can transition from any state to any state with ligand or without.0954

OK, this is the sequential model for binding.0961

Now, you should now, just because 2 models have been proposed, it does not necessarily mean that they are mutually exclusively.0965

We are not saying that it is either sequential or MWC.0971

The same protein can and will often demonstrate both.0975

Maybe, sometimes the binding will happen in a sequential pattern.0980

Maybe, the binding will happen in an MWC pattern, in a simultaneously pattern.0984

Again, when we propose models in science, we are not necessarily being exclusive of the other models especially, when it comes to something as complex as biochemistry.0988

Lots of things are going on, and we still do not have a full grasp on what and why.0997

That is what makes biochemistry so rich, so full, so exciting, such a fertile field for any of you that are interested in research- so many wonderful things to discover.1003

OK, that takes care of the cooperative binding of hemoglobin.1014

Now, we are going to go on, and I am going to talk about a couple of the other things, other ligands that hemoglobin actually binds.1020

As it turns out, hemoglobin does not just bind oxygen.1026

It binds hydrogen ion; it binds CO2, and it binds something called biphosphoglycerate, which is a molecule that regulates the extent to which it binds O2.1030

Now, let’s go ahead and discuss that.1040

Now, let me go back to blue; I like blue.1044

Hemoglobin, in addition to the oxygen, it also transports hydrogen ion and CO2.1050

Hemoglobin not only carries O2 to the tissues - I should say from the lung to the tissues - but also carries the hydrogen ion and CO2 from the tissues to the lung.1070

I mean, in terms of physiological efficiency, in terms of just efficiency alone, I mean, it makes sense.1114

Why are you going to have this molecule that is going to go, take the oxygen from the lung, deliver it to all of the tissues and then, you are going to have another molecule that has to bring those waste products, the CO2, and the hydrogen ion that are created by the metabolic processes the body needs to get rid of them?1119

Why have another enzyme, another protein floating around, that is just going to have to bring them back?1138

You can have the same molecule, hemoglobin, do double duty.1142

It will take the oxygen; it will bring back the H+ and the CO2.1146

It will take the oxygen, bring back the CO2; that is what is so amazing about this hemoglobin molecule.1150

I mean, it really is kind of, sort of, staggers the imagination when you think of this collection of a couple of a hundred of amino acids and look at it what it does and it does it so beautifully and so perfectly and for so very long- absolutely magnificent.1155

OK, let’s see here.1170

Now, very, very important, the H+ - excuse me - and CO2, they do not bind to the same site that O2 binds.1176

O2 binds to the iron in heme; the H+ and the CO2 do not bind to the iron in heme.1192

Actually I will not say Fe2+; I am going to say iron.1209

I am going to say 2+ 3+ because again, once it becomes...you know what, I am just going to say "does not bind to the Fe in heme"- there we go.1218

OK, the H+ binds to one of many amino acids that make up the protein- makes sense.1231

We have plenty of nitrogens and oxygens that can actually be protonated by this H+, so it can bind anywhere.1253

Now, CO2 binds to the NH2 group, to the amino group at the amino terminal - oops, excuse me - end of each subunit forming something called carbaminohemoglobin.1261

The name does not matter actually.1310

Again, a lot of these names, they are actually not that important; they are just extra fancy stuff that just really gets in the way.1317

As long as you understand that CO2 is actually binding to an amino group, that is at the amino terminal of each subunit, that is what matters.1323

Here is the reaction that takes place; let me go ahead and go back to...you know what, I think I will do this in red.1331

We have our CO2 molecule plus I will do H2N.1336

We have a C; this I going to be the amino terminal here, then, we have C, and of course, the polypeptide chain of the protein goes on.1344

This is the amino terminal end.1356

This reacts, CO2 reacts with this, and what you end up with is the following.1360

You end up with C - I will go ahead and make it a little bent here - N, H, C, H, N, C.1366

Yes, here we go; let's just make sure we keep track of all these atoms- there we go.1379

We end up with this thing right here.1386

OK, the amino terminal end of the subunit, OK, this amino group, it acts as a nucleophile.1390

It attacks here; it pushes these electrons up, and it binds CO2.1399

That is where the CO2 binds; now, let's go back to black.1404

OK, the CO2 produced in metabolic processes is converted to bicarbonate to make it soluble in aqueous solution.1412

OK, in some of the CO2 that is produced in metabolic processes, about 20% actually, is going to be bound to hemoglobin.1449

Hemoglobin is what is actually going to take it back to the lungs to release it; that is one of the things that you exhale.1457

Not all of this CO2 that is created in the metabolic processes is actually bound up by hemoglobin, only a part of it is, again, about 20%, maybe, 25%.1464

The other CO2 produced in metabolic processes, CO2 is not soluble in aqueous solution.1474

In other words, if I bubble CO2 into water, the bubbles come up because it is not going to dissolve in the water.1480

The only time that CO2 is actually soluble in water is when I put it under high pressure, which is what you get in soda.1488

That is why soda has the fizz.1495

What we have done is we have actually pushed CO2 into the water, and in that process, by putting all that pressure on it, we can make sure it stays in the water.1499

When it is in the water, it reacts with the water to form carbonic acid.1508

Well, the CO2 that is produced in metabolic processes, the part that is not actually attached to hemoglobin directly, is converted to bicarbonate in order to keep it soluble in aqueous solution in the blood, which is not a high pressure system - excuse me - under conditions of normal pressure.1512

When we do not have the pressure to actually keep the CO2 dissolved, we have to turn it to something else to make sure it does dissolved.1548

We have to turn it into an ionic species - bicarbonate, normal pressure - and here is what it looks like.1552

Let's see here; let me see.1563

Let me go to the next page here; what we have is CO2 is going to react with the H2O - OK - and it is going to produce HCO3- + H+.1570

OK, this reaction is catalyzed by an enzyme called carbonic anhydrase- very, very important enzyme.1588

We are not going to talk about it here, but you definitely want to know this carbonic anhydrase.1595

OK, here is your bicarbonate right here, OK, hydrogen bicarbonate, carbonate.1600

Notice that 1 of the things that is actually produced in this is H+.1608

High CO2 concentration actually ends up producing a high H+ concentration, high acid concentration, which means a lower pH.1614

That is what CO2 does; there is more CO2 in the body.1623

If you cannot exhale it fast enough, it is actually going to start producing H+, and it is going to start to lower the pH of the blood.1626

OK, high CO2 concentration lowers the pH because high CO2 concentration...what is not attached to hemoglobin will actually react with water to produce bicarbonate and hydrogen ion.1634

Alright, now, as we said - excuse me - hemoglobin accounts for about 40% of the H+ and about 20% of the CO2 produced in tissues during metabolic processes.1648

What happens to the rest, well, the rest is actually absorbed in this bicarbonate and carbonate buffer system.1688

This is part of the buffer system of the blood, the carbonate, bicarbonate buffer system, that controls the amount of CO2 and controls the amount of H+ in the blood to make sure that it remains at a reasonably stable pH, somewhere in the range of about 7.2.1695

OK, now, H+ and CO2 binding are inversely related to O2 binding, and you know what inverse means.1712

The more that hydrogen ion and CO2 bind, they cause conformational changes, which makes it less likely for O2 to bind and vice versa.1739

As more O2 binds, it makes it less likely for hemoglobin to bind CO2 and hydrogen ion.1748

This makes sense because of what hemoglobin does, delivers the O2, drops its pay load, delivers the O2 to the tissues.1755

Now that the O2 is no longer bound, now, it is going to pick the H+ and the CO2 and take it back to the lungs- it makes sense.1763

Now, under conditions of low pH - and again, low pH means high hydrogen ion concentration - and high CO2 concentration, the affinity - excuse me - of hemoglobin for O2 is lowered.1772

It releases its O2 to the tissues.1819

Again, the hemoglobin travels to the tissues.1831

The tissues tend to have a very, very high CO2 and a high acid concentration.1836

Under those conditions, the binding of O2, the affinity of hemoglobin for O2 drops.1840

When the affinity drops, it releases its O2, which is exactly what we want to happen.1850

It is not just pressure, the low 4 kPa pressure at the tissues versus the 12 or 13 kPa of the lungs.1855

It is not just the pressure that actually affects the extent to which hemoglobin will bind O2 or release O2.1863

It is also the presence of CO2 and hydrogen ion, and as we will see a little bit later, the presence of this regulating molecule called 2,3-biphosphoglycerate.1871

OK, now, in the lungs, as CO2 is released and the pH comes back up to normal - in other words, under conditions of normal pH - hemoglobin’s affinity for O2 rises.1883

Now, it wants O2, which is perfect because the lungs are flooded with oxygen gas.1913

It binds the O2.1918

Let’s try to make this a little bit more legible, shall we?1925

Hemoglobin's affinity for O2, it rises, and it binds oxygen, which exactly what we want it to do.1936

OK, now, let’s go back to blue here.1955

The effect of H+ and CO2 on O2 binding and release - well, there is a name for it - by hemoglobin is called the Bohr effect.1964

It is named after Christian Bohr, who was Niels Bohr father.1994

It is not a Niels Bohr effect; it is a Christian Bohr effect- the Bohr effect.1998

The extent to which the hydrogen ion and CO2 actually affect the binding and release of oxygen by hemoglobin, we give it the name the Bohr effect.2002

OK, now, let’s go a little bit deeper into this, not too, much but a little bit of detail is good.2012

A major contributor to the hydrogen ion Bohr effect is the histidine 146 residue on the beta subunits.2022

This beta subunit, it is a polypeptide chain.2063

The 146 amino acid on that chain is a histidine.2067

OK, now, under conditions of low pH...and again, low pH means high hydrogen ion concentration.2073

It is really, really easy to confuse that; I actually confuse it all the time.2090

When we talk about...which is why I personally prefer to talk about high hydrogen concentration, low hydrogen ion concentration because then, I am actually speaking about something that is high or low directly.2094

When we talk about low pH, because pH is a negative logarithmic scale, a low pH means high hydrogen ion concentration- very, very acidic.2106

High pH is low hydrogen ion concentration- very, very basic.2117

Again, in the literature and just in general, you are going to find that they use pH to describe concentration of H+ as opposed to directly saying high or low hydrogen ion concentration.2123

So, be very, very careful with that, stop for a second just to make sure you understand- low pH, high hydrogen ion concentration.2136

I will go ahead and put it in here: high hydrogen ion concentration.2143

And I know my brackets are not exactly pretty, but there it is.2149

OK, under conditions of high hydrogen ion concentration, low pH, this histidine 146 actually becomes protonated, which makes sense, and it forms an ion pair, in other words, an ionic bond, an ion-ion bond, ion pair with aspartate 94.2152

The aspartate 94, you have got a negative charge on it; the protonated histidine has a positive charge on it.2189

Well, negative and positive, they tend to attract each other; they form an ion pair.2196

OK, this ion pair, this positive negative attraction - OK - it actually stabilizes the T-state of hemoglobin, and the T-state is the deoxyhemoglobin state.2201

It is the state that does not bind O2 very easily; in fact, it wants to give up its O2.2227

Sure enough, the more the hydrogen ion concentration, the more acidic this histidine 146 is protonated.2233

It is going to form some ionic pair with this aspartate 94 that is going to, sort of, lock the hemoglobin in to this T-state.2242

It is not going to bind to O2; that is where this comes from.2251

It stabilizes the T-state, and the T-state is the deoxy state- deoxyhemoglobin.2256

OK, now, the bound CO2 that we saw earlier, that is bound to the amino terminal - OK - also forms ion pairs.2267

Again, when we bound the CO2, you notice that one of the double bonds actually moved up to the oxygen to form a negative bond on one of the oxygens.2292

The oxygen is carrying a formal charge of negative one.2301

That is going to form an ion pair with other things that happen to be positively charged, which also tends to stabilize the T-state.2304

The bound CO2 also forms ion pairs that stabilize T-state- both of them do, the deoxy.2313

OK, the conclusion, really, what we want you to take away from all of this is the fact that cooperative binding is profoundly complex.2329

Cooperative binding in hemoglobin - well, cooperative binding in anything that actually binds ligands - is a very complex function, in not only O2 but also H+ and CO2- there you go.2346

OK, now we are going to start.2378

Now, let's talk about the regulation binding, the hemoglobin’s binding of O2 via this molecule called 2,3-biohosphoglycerate- just BPG as what we call it.2383

Let’s start on that, and I think I am actually going to keep it in blue because I like the blue.2393

Regulation of O2 binding by 2,3-biphosphoglycerate, and by now, you are accustomed to this nice long words in biochemistry, otherwise known as just 2,3-BPG or just BPG.2400

Regulation of O2 binding by 2,3-biphosphoglycerate is heterotropic allosteric regulation.2436

OK, here we go; regulation of O2 binding by 2,3-BPG is heterotropic allosteric regulation2459

Let's recall what this means; remember we said we have this enzyme - not enzyme, this protein - that binds some ligand, in this case, O2.2467

Well, there is another site on this protein that another ligand combined, and this binding of this ligand can actually affect the extent to which the main ligand, the O2, binds.2478

Heterotropic means that it is a different molecule altogether.2492

Allosteric means it binds to another site on the protein and regulation is just regulation- that is all.2496

This is just a fancy word for the fact that there is another molecule that is going to control the extent to which O2 binds- that is all.2503

I mean in some sense, the H+ and the CO2 that we have talked about are also allosteric heterotropic modulators of O2 binding, but we tend to call 2,3-BPG, we tend to refer to that more so because it is a larger molecule; but for all practical purposes, they are all doing the same thing.2511

They are not the same molecule as O2, and they control how O2 binds.2532

OK, let's draw the structure for 2-BPG and see what is going on here.2538

Let’s see; let’s write 2-BPG.2543

We have got...let me do this...that is OK.2549

I will go ahead and do it in black; I have got C, C and C.2552

I will go ahead and do this as COO-; I will go ahead and just write this as PO32-, and I will go ahead and put a PO32- here.2559

That is fine; I will go ahead and put the hydrogens in- that is it.2573

2,3-biphosphoglycerate, this is the no. 1 - I will go back to blue - no. 2 carbon, no. 3 carbon, 2,3-biphosphoglycerate, this carboxylic acid a molecule right there.2577

OK, now I am going to go ahead and stay with blue here.2596

Now, BPG, the biphosphoglycerate is always present.2601

When we talk about biphosphoglycerate as regulating the amount of O2 that is binding, we are not talking about that it is not bound to hemoglobin, and then, all of a sudden, when BPG does bind to hemoglobin, things change.2605

The BPG is always bound to hemoglobin.2618

What we are discussing here is that when you go to higher altitudes, it is the increase in the BPG concentration on the blood.2621

Therefore, more BPG starts to bind to hemoglobin.2628

BPG is always present.2633

In fact, the normal binding curves that we saw in previous lessons for hemoglobin, that actually includes the bound BPG that is always there with the hemoglobin.2639

OK, in fact, the standard binding curves we have discussed, or I should say we have seen so far, involve hemoglobin with bound BPG.2654

I repeat again, we are concerned not with the binding of BPG.2681

We are concerned with the binding of more BPG.2685

OK, now, let me see the binding of BPG.2691

BPG and hemoglobin’s affinity for oxygen, again, are inversely related.2700

What that means is, as the BPG concentration rises, that means that the affinity for O2 by hemoglobin, drops.2718

That means, hemoglobin does not want O2 as badly as it did before.2730

Hemoglobin's affinity for O2 decreases.2737

As the BPG - let me make this arrow a little bit better - concentration increases, well, when a concentration increases, more BPG is going to bind to hemoglobin.2745

That causes hemoglobin to have less affinity for O2; it is going to want to get rid of its O2, or another way of looking at it, it does not want to bind O2 as strongly.2757

It just depends on your perspective.2765

OK, let’s take a look and see what is going on; let’s say a few more words actually, and then, we will go ahead and draw what this looks like.2769

We will draw a couple of binding curves, standard binding curve and then, the binding curve with the extra BPG that is bound to the hemoglobin.2774

Now, at sea level - that is fine, I will go ahead and stay with the blue - the BPG concentration is somewhere in the neighborhood of 5mM.2784

Now, at about 4500 feet, as you go up to about 4500 feet or 5000 feet, now, what happens is the concentration of BPG in the blood starts to increase - OK - and it actually is about 8mM.2804

The concentration of BPG goes up, so more BPG is going to bind to the hemoglobin.2827

Now, here is what is important; here is how this works.2831

BPG does not - repeat - does not affect the binding of O2 very much in the lungs but effects the release of O2 in the tissues very, very much.2837

I will write very, very much.2880

OK, let me talk a little bit about what is actually happening here.2887

Now, recall that at sea level, that hemoglobin delivers about 40% of the oxygen that is bound to it, delivers about 40% of its bound O2.2891

OK, 100% saturated hemoglobin is fully saturated with O2.2920

It only delivers in the blood; only about 40 % of the oxygen that is available is delivered to the tissues.2926

It keeps about 60%.2930

Now, well, let me go ahead and write it out and then, discuss it.2934

At high altitudes, the availability of oxygen is less.2942

In other words, the partial pressure of oxygen is less.2953

There is less oxygen; that is all that means.2956

The pO2 is reduced; OK, there is less oxygen.2958

The pO2 is reduced, so less O2 binds to hemoglobin.2966

Therefore, less O2 is delivered to the tissues.2979

Now, this is before anything happens; OK, this is before any BPG happens.2992

If I am at sea level, 40% of my oxygen that is bound to the hemoglobin is being delivered to my tissues.2996

If I, all of a sudden, take a plane, take a train, whatever, and all of a sudden, I am at 4500 feet sea level, well, there is less oxygen up there.3002

Before anything happens in the body, all of a sudden there is less oxygen binding to the O2.3010

However, the body will still only deliver up to a certain amount, but because there is less O2 having bound, there is less O2 delivered; and here is what it looks like pictorially.3016

Let's say that this is a 100% here and here; OK, now, let’s say this is a 100% of O2.3030

Well, we said that it binds; we said that it releases about 40% of it.3036

About that much is released; this right here, this remaining 60%, that stays bound.3041

Well, if you go to higher elevation, before anything happens, OK, before BPG has a chance to do what it does, now, instead of binding a 100%, now, it is binding 90%.3047

There is less oxygen to bind; all of the hemoglobin is now no longer saturated.3058

However, when it gets to the tissues, it still releases that amount, that same amount.3063

Now, instead of 100%, now, because less is bound, it is still going to deliver the same amount from the 0 mark.3069

Now, instead of delivering this much, it delivers this much.3080

The bottom end, the delivery end, that stays the same, but because there is less oxygen bound to hemoglobin, there is less oxygen delivered because hemoglobin will always keep about 60% of its oxygen.3086

From 60 to a hundred is 40, but now, if only 90% is saturated, 60 to 30 is 30%.3103

That is how our bodies experience the diminished oxygenation.3106

It is because it delivers the same level, but there is less to deliver.3111

What BPG does is at higher elevations, once the BPG concentration rises, the BPG binds to the hemoglobin.3118

Now, it does not affect too much, as far as the binding of hemoglobin in the lungs.3127

Let's say from a 100%, it binds 90%, but now, instead of delivering from 60-90, now, what happens, is it actually ends up delivering more.3133

Now, the 40% or the 60% drops down to 50 to 40 to 30.3145

Although, it does bind less because of the increased BPG concentration, it ends up delivering more, so here, here, here, here.3152

OK, once I have gone to a higher elevation, yes, it is true that less has bound, but now, I am dropping this down here.3165

So, more is delivered, and it brings it back up to the 40% level, which was the original amount that the body needs in order to sustain its natural function.3175

Do not worry about this; I am going to actually write it out and then, I am going to show you what this looks like on a graph on a binding curve.3185

I will be discussing this again in just a moment; let me just go ahead and write a few things down here, though.3192

Now, OK, what did I write?3198

At high altitudes, the PO uses less oxygen to bind, therefore, less O2 is delivered to the tissues.3203

Yes, now, BPG concentration, it rises.3208

Once the BPG concentration starts to rise, the body is adjusting for the higher elevation by raising the concentration of BPG.3221

Higher concentration of BPG, it starts to bind to hemoglobin.3228

BPG starts to bind to the hemoglobin.3233

OK, as more binds, it causes hemoglobin to lose affinity for its oxygen/O2 but not so much at the pressure of the lungs, rather, very much at the pressure of the tissues.3242

OK, again, I have a certain amount of hemoglobin, 100% saturated, OK, 0, 100- that is like that.3301

It is going to deliver about 40% of its payload; it is going to keep 60%.3307

Well, now, I go to higher elevation; the BPG, it is true that it ends up dropping from about...the BPG causes the O2 to bind a little bit less in the lungs.3312

Now, I am about 90% saturated, but because it causes hemoglobin to lose affinity for oxygen, it actually causes more of it to release.3321

Even though I have dropped this to 90%, the 60, the 90 is 30, but now, it is no longer 60.3334

Now, it releases up to 50, 40 and even more.3341

If it releases now 50% instead of 60%, now, the difference between 50 and 90 is back up to 40%.3347

As far as the body is concerned, it is still getting the oxygen that it needs.3354

We have just gone to this much to this much; we have dropped the lower end.3360

It binds a little bit less, but it releases a whole lot more once it gets to the tissues.3365

I hope that make sense; OK, now, let’s go ahead and draw this out, and I think it will make sense.3371

Let me go to the next page here, and let me go ahead and draw the axis in black.3381

I have got this; I have got that.3388

OK, now, this is going to be 1; we are doing a binding curve here.3393

These are percentages, and this is going to be 0.3401

This is going to be 0; this is pressure.3406

OK, this is going to be partial pressure of O2, and we are going to go ahead and use kPa; and this right here, is the percentage of O2 actually bound.3412

I am going to go ahead and mark this as 4.3423

This is 8; this is 12.3425

This is 4kPa, 8kPa, 12kPa.3428

Now, you remember, this 4kPa, that is about the pressure at the tissues, and just about 12 or 13kPa, that is the pressure in the lungs at sea level.3432

At 4500 feet, the pressure in the lungs is about 7kPa; let’s go ahead and mark those points off.3446

I am going to mark those points in red; I am going to put a little X here, and I am going to put a little X here.3451

And now, let me go ahead and draw some lines.3458

Actually, let me go ahead and draw that; yes that is fine.3462

I will go ahead and draw the lines.3464

That is there; that is there, and that is there, and I will go ahead and label everything in just a minute.3469

Now, let me go ahead and draw my lines here.3481

This is going to be the normal binding curve at sea level, and remember, it is going to be, sort of, sigmoid.3486

Let me mark a couple of points, though, so just I know where I am.3492

Let me go ahead and go over this way.3499

OK, it is going to be something like that.3503

It is going to look something like that, the normal sigmoid binding curve.3510

OK, now, let me go ahead and do my labels here.3515

This point, this is the - I am going to do this in black - partial pressure of O2 in the tissues.3519

OK, partial pressure is 4kPa.3530

OK, now here, this is going to be the partial pressure of O2 at 4500 feet elevation.3534

Here, this is going to be the partial pressure of O2 at sea level- normal.3541

OK, that is what is going on.3550

Now, let me go ahead and draw the other cure before I discuss distances.3554

I am going to do this curve, I think in...that is fine.3558

I will go ahead and do it in blue also; that is not a problem.3562

Let’s make sure this is blue; now, this is going to be here, and it is going to be here- something like that.3567

OK, this graph, that is the graph with no BPG or normal BPG.3582

OK, this graph right here, is the binding curve for hemoglobin under conditions of elevated BPG concentration - OK - elevated BPG, or I will put extra bound BPG.3595

OK, now, let’s take a look at what happens; I am going to go ahead and do this in red.3623

Under normal conditions - OK, we are going to follow this top curve right here, OK - it is going to go ahead and - you know what, I am going to do it in black, I am sorry, OK - bind at about 12 or 13kPa.3627

It is going to bind to oxygen in the lungs; now, at the tissues, it is going to be right there.3644

The distance between here and here, this distance, that is the 40%.3651

OK, under normal conditions, that is what happens.3658

Now, let’s go ahead and go all of a sudden to 4500 feet, before any extra BPG has bound.3661

So, we are still going to follow the top curve.3667

Now, under conditions of 4500 feet, now, the pressure in the lungs is here.3672

It is going to bind that much oxygen, but still it is going to release that much.3676

Now, there is your 30%.3683

That is what your body experiences; from normal sea level, all of a sudden, if you jump up to a high altitude before the body has had the chance to adjust the BPG concentration, all of a sudden you are delivering less oxygen from 40% to 30%.3687

OK, now, after the body has had a chance to adjust, a couple of hours, a couple of days, BPG concentration in the blood goes up.3700

The BPG binds to the hemoglobin; now, the hemoglobin is going to behave differently.3710

It has less affinity for oxygen, so the binding curve is going to be different.3716

Now, we are going to follow this curve right here.3720

OK, now, at 4500 feet, it is going to bind that much.3724

It is going to bind less but not too much less, but now, at the pressure of the lungs, but now, as it makes its way to the tissues, now, let’s go to the tissues, come down this curve.3731

Now, look where we are; the binding in the lungs has diminished a little bit, but the release of the O2 in the tissues has increased a lot.3743

Now, this distance right here, that distance is back up to the 40%, in fact, more that 40% sometimes.3753

That is what is going on.3763

This is absolutely extraordinary; there is less oxygen available at higher elevations, and the body knows this.3768

It can only do what it can with what is available to it.3775

If less oxygen is available, the body adjusts at the lower end that says: OK, if I am going to keep 60% of my payload, now, instead I will keep 50% of my payload.3781

A certain amount has bound, but now, I am going to release more of it because, again, it wants to be at the 40%.3796

By releasing more, it brings it back down to the 40% despite the fact that there is less oxygen at higher elevation.3804

Again, it does not make too much of an adjustment at the high end; it makes the adjustment at the low end to bring the delivery back up to normal.3812

And again, that is all the tissues are concerned about; it is the tissues that want the oxygen.3820

That is where you notice it; you do not notice it in the lungs.3824

You notice it because less oxygen is being delivered to the tissues; well, if BPG ends up causing more oxygen to be delivered to the tissues, your body does not notice.3828

It is just going to function normally again as if it were at sea level; that is what is important.3837

OK, now, let’s go ahead and circle these points because these are the important ones- over here.3843

Here, the binding of O2 in the lungs at this higher elevation is only slightly diminished or decreased.3851

Here, the release of O2 in the tissues is greatly increased creating more of a gap to bring us back up to that 40%.3871

That is what is happening; OK, this top curve is normal hemoglobin under standard sea level conditions.3902

This curve is after BPG has had a chance to have its effect.3909

Now, the binding of oxygen has changed and by picking 2 points, we can actually see the numbers, from here to here, 30%, from here to here 40% under normal conditions.3915

Now, under BPG conditions - once the BPG has had a chance to do its magic - now, it binds less oxygen, but it releases so much more oxygen bringing the number back up to the 40% that the body is accustomed to.3930

That is all that is going on; now, I will finish off by saying, BPG binding, it does effect O2 affinity but not equally at both ends, in other words, the lung end and the tissue end or the lung end and the tissue end.3945

It affects it tremendously at the tissues end I will say.3993

The delivery of O2 is brought back to about 40%.4014

I hope that made sense.4030

Thank you for joining us here at Educator.com; we will see you next time, bye-bye.4032

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