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Raffi Hovasapian

Raffi Hovasapian

Enzymes V: Enzyme Inhibition

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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Lecture Comments (13)

0 answers

Post by Raymond Santiago on March 23, 2017

How would the graph of mixed inhibition look like if:

Vmax decreases as usual but Km decreased as well... There would be no interception?

1 answer

Last reply by: Professor Hovasapian
Tue Nov 29, 2016 3:07 AM

Post by Parth Shorey on November 28, 2016

How come you didn't go over non-competitive inhibition?

3 answers

Last reply by: Professor Hovasapian
Mon Feb 16, 2015 3:18 PM

Post by Billy Jabbar on April 28, 2014

Great Lecture, but I just want to point out that your expression of both KI and KI' are reversed.  My book and professor presented it the opposite way.

Regardless though, all of the other concepts that include KI were the same so aside from that discrepancy, everything else is okay.

0 answers

Post by tiffany yang on November 14, 2013

along with Cuong's question, can you please explain why reversible inhibitor will not decrease Vmax' whereas irreversible inhibitor will decrease the Vmax? Thank you professor Hovasapian.

If Vmax doesn't change for reversible inhibitor, does that mean V knot when substrate concentration equals to Km doesn't decrease either?

Does reversible inhibitor just means it has a good chance to fall off? so substrate can come back in to bind with enzyme? Thank you so much.

1 answer

Last reply by: Professor Hovasapian
Tue Sep 24, 2013 8:07 PM

Post by Vinit Shanbhag on September 15, 2013

most of the feedback inhibition in metabolic pathways happens thru allostery,, my question is: will those inhibition modes follow the same principles in this lecture?

If your drug is a small molecule which is binds to non enzymatic protein, how shld we express the effect of its inhibition?

2 answers

Last reply by: cuong Le
Mon Apr 1, 2013 1:47 PM

Post by cuong Le on April 1, 2013

For the irreverisble inhibition, what are the graphs look like? Can you please briefly mention?

Enzymes V: Enzyme Inhibition

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
  • Enzymes V: Enzyme Inhibition Overview 0:42
    • Enzyme Inhibitors Overview
    • Classes of Inhibitors
  • Competitive Inhibition 3:08
    • Competitive Inhibition
    • Michaelis & Menten Equation in the Presence of a Competitive Inhibitor
    • Double-Reciprocal Version of the Michaelis & Menten Equation
    • Competitive Inhibition Graph
  • Uncompetitive Inhibition 19:23
    • Uncompetitive Inhibitor
    • Michaelis & Menten Equation for Uncompetitive Inhibition
    • The Lineweaver-Burk Equation for Uncompetitive Inhibition
    • Uncompetitive Inhibition Graph
  • Mixed Inhibition 30:30
    • Mixed Inhibitor
    • Double-Reciprocal Version of the Equation
    • The Lineweaver-Burk Plots for Mixed Inhibition
  • Summary of Reversible Inhibitor Behavior 38:00
    • Summary of Reversible Inhibitor Behavior
    • Note: Non-Competitive Inhibition
  • Irreversible Inhibition 45:15
    • Irreversible Inhibition
    • Penicillin & Transpeptidase Enzyme

Transcription: Enzymes V: Enzyme Inhibition

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

Today, we are going to continue our discussion of enzymes by talking about enzyme inhibition.0004

Enzyme inhibition exactly is exactly what you think it is.0009

We have an enzyme that does something; we want to either completely stop it from doing something, or we want to slow it down a little bit.0014

There is also something called positive inhibition, where you want to actually cause an enzyme to do what it does a little bit better, a little bit faster; but for the most part, we are going to be talking about negative inhibition.0022

Again, inhibition, exactly what you think it means, so let's get started and see what we can do.0036

OK, enzyme inhibitors - excuse me - are molecules that interfere with enzyme action or enzyme activity.0043

Now, it is no surprise that a large percentage of current pharmaceuticals on the market are, in fact, enzyme inhibitors, and that is a huge, huge, huge area or pharmaceutical research.0076

We discover some metabolic pathway; we discover something in that pathway, some enzyme where we know how to control it.0117

We control it; we mess with it- that is what we do.0125

OK, now, there are 2 broad classes of enzyme inhibitors.0128

Excuse me; we have something called reversible and - exactly what you think - irreversible.0140

Now, let's go ahead and deal with the reversible first; let me go ahead and do this in blue.0152

Now, the reversible comes in 3 varieties: something called a competitive inhibitor - it is exactly what you think it is, but we will give a definition in just a minute - and uncompetitive inhibitor and a mixed inhibitor- mixed being combination of competitive and uncompetitive.0161

OK, let's go ahead and deal with these one at a time; the first thing we are going to deal with is competitive inhibition.0187

It is the most intuitive one; the one that is most easily understood.0194

Competitive inhibition is exactly what you think it is, exactly what it sounds like.0199

It is where the inhibitor, which again is a molecule, where the inhibitor molecule, it competes directly against...I will stay with actually, instead of against, does not matter.0212

It is competing with the normal substrate for binding to the active site.0239

It competes directly with the normal substrate for the active site.0244

They both want to be in the active site- substrate competitor.0260

If substrate makes it, the enzyme does what it does; if the competitor makes it to the active site before the substrate does, that is it.0264

It blocks off entrance to the active site for the normal substrate.0271

Excuse me; pictorially, it looks something like this.0279

Let's say you have some enzyme, it looks something like this.0284

OK, excuse me.0290

Let's say our normal substrate looks like that.0295

When the enzyme and the substrate come together - I will put S here, and I will put E for enzyme - we end up with our enzyme substrate complex.0300

Well, the inhibitor, let's say it looks something like that.0312

Now, if the enzyme binds to the inhibitor, you end up with something called the enzyme...this is the enzyme substrate complex.0323

You end up with something called an enzyme inhibitor complex, and now, because this inhibitor is occupying the actual active site of the enzyme, the substrate, itself, cannot come in.0338

It has blocked the enzyme it has inhibited- that is it.0349

Whatever metabolic pathway happens to be involved, it stops at that pathway.0352

It does not do what it is supposed to do; this is competitive inhibition- competition for the active site.0357

In terms of the Es and Ss that we were talking about, before it looks something like this.0364

You have the enzyme plus you have the substrate.0368

They can form something called the enzyme substrate complex that can go on to form enzyme plus product.0372

Now, the enzyme, instead of binding to the substrate, can also bind to the inhibitor forming the enzyme inhibitor complex.0378

This is what it looks like in terms of Es and Ss and things like that.0388

Now, let's go ahead and for this, I am going to introduce something called ki.0393

I just want you to be aware of it; I will write it again.0400

This ki is not a rate constant; this is an equilibrium constant.0405

Here, this ki is equal to the concentration of Ei over the concentration of E times the concentration of I.0411

That is this reaction right here, the equilibrium.0425

It is the dissociation reaction for the enzyme inhibitor complex- OK, products over reactants.0429

These are the reactants; this is the product.0436

This ki, it is the equilibrium constant for the formation of enzyme inhibitor complex, or it is the dissociation constant, if you will, for this complex that way, depending on which direction you want to take it.0438

It is just an equilibrium complex; OK, it will show up a little bit later, but we are not really going to be doing too much with it.0451

It is just something that you should know.0458

OK, now, the Michaelis-Menten equation in the presence of a competitive inhibitor looks like this: v0 = Vmax S, so far so good, alpha Km + S.0462

Now, we have this alpha factor; here, alpha is equal to 1 plus the concentration of inhibitor, oops, ki not Km, right?0505

Yes, they were ki, and ki, as we said, is equal to Ei/E and I.0523

These do not matter all too much; this is what is important, this alpha.0543

Just consider it some number, which is generally going to be bigger than 1.0548

It is the whole idea; it is going to be bigger than 1.0552

OK, it is just some factor, which in this case, is related to the inhibition.0555

OK, now, let's see what we have here.0563

OK, this right here, this alpha Km, this is the observed Km, often called the apparent Km.0569

Remember what Km was; Km was the concentration of substrate that allows you to react at which you are at half maximum velocity.0589

This observed Km is the...you have the normal enzyme, and then, you put this competitive inhibitor into the solution.0600

Now, you are going to experience a new concentration that will take you to half velocity.0610

That is what this is, and we will talk a little bit more about that in just a minute.0617

This is the observed Km, this whole quantity.0620

OK, this is the observed Km, which, again, is the amount of substrate needed to bring you to 1/2 of the maximum velocity.0624

Now, here is what is interesting.0650

Since the substrate and the inhibitor are in direct competition, all we need to do in the presence of a competitive inhibitor...well, again, chemical reactions happen by things running into each other.0657

If you have a whole bunch of substrate molecules, very little inhibitor molecule and some enzyme, well, most of the enzyme is going to be tied up with substrate molecules because they form the majority of the molecules that are bumping into it.0690

If you increase the inhibitor concentration, now, there is a greater probability that that inhibitor will bind to the enzyme, and, of course, it is going to slow the enzyme down.0702

Well, in order to just speed things up again and get things back to where they were before, all you have to do is increase the substrate concentration.0712

No matter how much inhibitor you put, as long as you keep increasing the substrate concentration so that there is so much substrate compared to inhibitor, statistically, more substrate is going to run into the enzyme, and you are going to get back your initial velocity.0719

Km, the amount of substrate that you need in order to achieve half maximum velocity, you throw some inhibitor in there.0735

All of a sudden ,you throw some inhibitor in there, and all of a sudden, the velocity is going to slow down because, now, some of the enzyme is going to be bound up with inhibitor molecule instead of substrate.0745

Well, in order to get it back up, you increase the substrate concentration.0752

Now, you have increased the substrate concentration, and you bring the velocity back up to half Vmax.0757

You add some more inhibitor; well, you add some more substrate to bring velocity back up again to where Vmax was.0763

In competitive inhibition, the maximum velocity does not change.0772

The only thing that changes is the amount of substrate you have to add - normal substrate - in order to bring it up to half velocity.0776

In other words, it is Km that changes, and we will show you that mathematically.0784

Since S and I are in direct competition, all we need to do is increase the substrate concentration in order that more substrate and enzyme come into contact.0790

In this case, in the presence of a competitive inhibitor, the maximum velocity of the enzyme does not change.0815

The competitor does not affect the maximum velocity of the enzyme; it affects how much substrate you have to put in to reach that maximum velocity.0824

In this case, what an inhibitor does, it actually slows down the enzyme action.0831

It does not stop it altogether; it just depends on what the concentration of enzyme and inhibitor is.0838

If you have so much more inhibitor than enzyme, then yes, you are just going to completely eliminate substrate from knocking into the enzyme at all.0842

So, you are going to stop it, but really, what a competitive inhibitor does, it slows the enzyme action down.0850

In this case, in the presence of a competitive inhibitor, maximum velocity does not change.0857

Only Km changes, and it changes by a factor alpha; and you remember that alpha depends on how much inhibitor there is.0868

OK, now, let's look at the double reciprocal version of this Michaelis-Menten equation for competitive inhibition.0878

Let me do this one back to black.0887

Now, the double reciprocal version of the Michaelis-Menten equation is the following.0891

It is 1/v0 = alpha Km/Vmax x 1/S + 1/Vmax.0910

You notice, the intercept 1/Vmax, the Y intercept, what Vmax is, it does not change.0926

Here, Y intercept stays the same.0936

Vmax stays the same.0943

What does change is the slope; that was the slope - right - of the Lineweaver-Burk plot?0951

The slope changes by a factor of that much; in other words, the slope goes up.0957

From your perspective, the slope goes up; I will have a picture in just a minute.0961

Slope rises as inhibitor concentration rises - right - which is alpha.0967

That is what alpha measure; it measures how much inhibitor is there.0975

As this number goes up, it is greater than 1, the Km/Vmax goes up.0978

From your perspective looking at the graph this way, your line is going to go like that.0982

Slope rises so Km decreases, and I will show you why in just a minute.0987

OK, now, let's go ahead and look at an image here.0998

There we go; we might say that this one is no inhibitor.1003

As we move up, as we increase our inhibitor concentration, what happens...we said Vmax does not change.1013

The Lineweaver-Burk plot literally just goes from here; it just switches.1020

The slope rises, rises, rises; well, the Vmax is not changing, but now, the absolute value of 1/Km is actually the absolute value of 1/Km.1025

1/Km is getting closer to 0.1040

Numerically, it is rising because the -1 is bigger than -6, but the absolute value of the 1/Km is getting smaller.1045

It is getting closer to 0; well, if the absolute value of 1/Km is getting smaller, that means Km is getting larger.1054

That is what happens here; in competitive inhibition, the maximum velocity does not change.1061

What changes is the amount of substrate you have to have in order to get back to your half maximum velocity.1067

Competitive inhibition slows down the reaction.1074

It decreases the...I am sorry, increase the Km; it decreases the 1/Km.1082

That is what is happening here; the graph looks like this.1087

As you add inhibitor, you are going to get...the more inhibitor you add as you increase inhibitor concentration, the slope of your graph is going to change, but your Vmax is not.1092

It is going to rotate around that point; that is what is happening.1102

Again, notice that Vmax does not change, but absolute value of 1/Km decreases; so Km increases.1108

And again, it makes perfect sense; the Km increases.1137

You just need to add more substrate in order to allow more substrate molecules to run into the enzyme, in order to get back up to half velocity.1141

Inhibitor slows you down; bringing the substrate concentration back up brings you up.1149

That is what this says; this confirms that Vmax stays the same.1153

Km increases; OK, that is competitive inhibition.1157

Now, let's talk about uncompetitive inhibition; let me go back to blue here, so uncompetitive inhibition.1164

You are probably wondering why did not we call it non-competitive inhibition.1178

Non-competitive inhibition is a special case that happens virtually never experimentally, but it is a special case that we will talk about a little bit later after we talk about mixed inhibition.1182

In order to differentiate it, instead of calling it non, we call it uncompetitive inhibition.1195

Now, uncompetitive inhibition is when your inhibitor molecule binds to a site other than the active site, but it binds only to the enzyme substrate complex.1200

In other words, it binds only after the normal substrate has bound to the enzyme active site, only after the normal substrate is attached.1242

I will just write "is attached" instead of "has bound"; again, uncompetitive inhibition, it looks like this.1271

You have enzyme plus substrate to form something called the enzyme substrate complex.1278

This enzyme substrate complex can break down into enzyme + product, or at this point, the inhibitor can bind to form this enzyme substrate inhibitor complex.1286

Here is an enzyme that has 2 substrates; it has 2 places where things can bind: the normal active site for the normal substrate and some other place on the enzyme or inside the inside the enzyme where an inhibitor can bind.1302

It does not compete with the active site; the substrate binds directly, but at that point, after it is bound, now, the inhibitor gets in the way.1314

It competes indirectly in an uncompetitive fashion.1325

OK, now, for uncompetitive inhibition, the Michaelis-Menten equation looks like this.1330

What you have, now, is v0 = Vmax x the substrate concentration.1346

Again, the numerator stays the same; now, Km is there, plus we are going to have something called alpha prime times substrate concentration.1353

Now, alpha, instead of affecting the Km, it is going to affect the substrate concentration.1362

This is what the form is, and again, alpha prime is equal to 1 + inhibitor concentration/ki prime and ki prime is equal to the equilibrium constant for the formation of the enzyme substrate inhibitor complex from the enzyme substrate complex and inhibitor.1368

That is what that is; I just want to think of it as some number bigger than 1 that is going to have...it is a measure of the uncompetitive effect.1399

OK, let's go ahead and see what is happening here.1408

Now, for high substrate concentrations, this equation, the above equation, becomes v0 = Vmax/alpha.1413

In this case, uncompetitive inhibition Vmax does change, and since alpha prime is a number that is going to be greater than 1, the maximum velocity actually decreases.1444

It really slows down the enzyme; it slows it down from the top end.1464

It makes it so you cannot achieve a maximum velocity, or the maximum velocity that you did achieve without the inhibition is, now, difference, is, now, cut-down.1469

Now, you have a maximum speed that you can get to no longer...it just completely slows it down from the top.1480

It does not just affect it, so that if you add more substrate nothing happens.1487

It just literally shuts down the maximum velocity.1492

OK, Vmax does change via alpha.1496

Now, recall that for the competitive inhibition, we had v0 = Vmax x S/alpha Km + S.1503

For high concentrations of substrate in competitive inhibition, for high substrate concentrations, this term goes away.1525

The SS cancels.1536

For high S, v0 still equals Vmax.1541

Again, it confirms what we already know that Vmax does not change for competitive inhibition.1548

Vmax changes for uncompetitive inhibition.1553

Let me see; now, let's do the Lineweaver-Burk plot for uncompetitive inhibition.1559

The Lineweaver-Burk equation for uncompetitive is the following: 1/v0 = Km/Vmax - let me actually put that one in parentheses and not the 1/S - x 1/S + alpha prime/Vmax.1569

In this case, notice, the slope stays the same.1606

The slope does not change.1614

The Y intercept changes; since the Y intercept changes, alpha prime is bigger than 1.1625

1/Vmax, that is the Y intercept; alpha prime/Vmax or alpha prime x 1/Vmax, it is going to raise the Y intercept.1638

As 1/Vmax, as the Y intercept goes up, the Vmax goes down.1650

And again, you will see that in just a second; the Y intercept changes.1658

A graph of this looks as follows; again, we have something like that.1665

That has no inhibition at all.1676

OK, your Vmax, your Km or actually this is your 1/Vmax.1680

This is your -1/Km; the Lineweaver-Burk plot that we just wrote down, the slope does not change.1686

The Y intercept changes; it goes up.1696

Now, every time you add uncompetitive inhibition, you get a new line.1699

You add more inhibitor; you get a new line.1704

Inhibitor, you get a new line; here is increasing inhibitor concentration.1706

As you increase the concentration of uncompetitive inhibitor, the Lineweaver-Burk plot starts to climb by a factor of alpha prime.1712

As the Y intercept goes up, Vmax goes down.1725

Here, notice, well, since the slope does not change, now, the absolute value of the Km is getting larger.1728

Its absolute value of 1/Km is increasing.1740

It is going farther and farther and farther away from 0, so Km decreases.1747

In this particular case, in uncompetitive inhibition, not only does Vmax decrease.1757

Here, Y intercept increases, so Vmax decrease.1764

In the case of uncompetitive inhibition, not only do you change the maximum velocity, you also change the Km.1776

You change the observed amount of substrate that you have to add in order to reach half maximum velocity, and it changes proportionally.1784

The slope does not change, so your maximum velocity goes down.1797

Well, sure enough, if your maximum velocity goes down, your Km is going to go down, and that is what this confirms.1801

Maximum velocity goes down as the intercept goes up; as you add uncompetitive inhibitor, it also changes the Km.1809

In the case of uncompetitive inhibition, both Km and Vmax change.1816

They decrease; we will have a summary of all this, of course, at the end.1822

OK, now, let's see what happens.1827

Now, let's go to our third...let's go back to blue here.1832

Let me draw a little bit of a line; this is going to be called mixed inhibition.1836

This is the third of our reversible inhibition processes.1843

Mixed inhibitor, OK, this is where the inhibitor molecule, again, binds to a site other than the active site for the normal substrate.1850

It also binds, I will just say somewhere other than the active site, but it can bind before the substrate attaches or after the substrate attaches.1868

It can bind either to enzyme directly before the substrate, or it can bind to the enzyme substrate complex, in other words, after the substrate has bound.1902

Here is what it looks like in terms of Es and Ss.1918

You have your enzyme; you have your substrate, and you have your enzyme substrate complex.1922

Well, the enzyme, instead of binding to the substrate first, it can certainly bind to the inhibitor, and it forms something called an enzyme inhibitor complex; and this enzyme inhibitor complex, now, it can bind with substrate to form the enzyme substrate inhibitor complex, or what can happen is enzyme can bind to the substrate like normal, and then, this enzyme substrate can bind to inhibitor to form this thing- that is it.1928

That is what is going on here; here is ki.1960

Here is ki prime; again, it is a little bit of a combination mixed.1965

It is exactly what you think it is; it is a bit of a combination of competitive inhibition that is this one right here and uncompetitive inhibition, which is this one right there.1970

The Michaelis-Menten equation for mixed inhibition is exactly what you think.1986

It is a combination of the 2; the alpha and the alpha prime show up.1996

We have Vmax times the substrate concentration over alpha-Km from the competitive inhibition + alpha prime x S from the uncompetitive inhibition.2000

if we do a double reciprocal of this, it is going to look like this.2015

The double reciprocal version, in other words, the Lineweaver-Burk version of the equation, it is going to be 1/v0 is equal to alpha-Km/Vmax.2023

Do that, and I will do 1/S here plus alpha prime/Vmax.2045

In this particular case - let's go to black - the slope changes, and the Y intercept changes.2052

In this particular case, again, Y intercept changes, so it is going to change the Vmax.2069

The slope is going to change.2075

Under ideal conditions, you will not change the Km, but experimentally, that never shows up.2080

That is what would be called non-competitive inhibition.2084

It is where the Km does not change but the Vmax does.2088

Experimentally, you will not run into that; mixed inhibition is actually a lot like uncompetitive inhibition in a sense that both things change.2092

The graph looks like this.2100

A Lineweaver-Burk plot ends up looking something like this.2104

We have normal; we will just call that one normal no inhibitor.2109

What ends up happening is the following; when you end up having inhibitor - let me go ahead and use red - you are going to get...actually, let's make this a little bit better here.2114

That one is not quite as clear as I want it to be; let me redraw this line.2127

This is normal; let me mark that as...there is no inhibitor there, and then, for red inhibitor, what we end up with is...in this particular case, you are still going to get to this point where the line is going to rotate, but now, what is happening is the uncompetitive inhibition is changing the Vmax, and the competitive inhibition is changing the slope.2132

So, you have vertical movement as well as slope changing.2169

The point where they meet is not going to be on the axis; it is going to be a little bit to the left of the axis.2173

What ends up happening is yes, you are going to have Vmax is going to change.2179

Inhibitor concentration is going this way; as you add inhibitor - in this case it is going to be a mixed inhibitor - you are going to have the uncompetitive component, which is going to change the Vmax.2187

So, as the Y intercept increases, the maximum velocity decreases, and you are also going to be changing the Km.2204

What is going to end up happening is the absolute value of the Km is actually going to be getting smaller.2214

The Km is actually going to rise; this is a combination of competitive inhibition and uncompetitive inhibition.2219

However, just because it is a combination, mixed inhibition is still an inhibitor that binds somewhere else on the enzyme.2227

That is the important thing to remember; as far as physically is concerned, it is still not directly competing with the active site for the normal substrate, but it is showing behavior of a competitive behavior.2240

It is showing some competitive behavior, but it is also showing uncompetitive behavior; so it is just a combination.2256

That is why you have both the alpha prime and the alpha; it looks something like this.2263

In this case, Km does change, and Vmax changes.2268

Vmax goes down; the Km goes up.2272

OK, now, let's go ahead and do a summary of what it is that we have here, so a summary of reversible inhibitor behavior.2278

OK, before I write this down, I am not sure what it is that your teacher is going to ask of you in terms of recognizing inhibition behavior.2300

My guess is that you are not going to be asked to know the form of the Michaelis-Menten equation for the different types of inhibition, and you are certainly not going to be required to know the double reciprocal version of the equation for the various inhibition behavior.2313

My guess is that the only thing that you are going to be asked to recognize is what the Lineweaver-Burk plot looks like for the various types of inhibition behavior.2327

Competitive: slope changes; Vmax does not change.2336

The Km increases.2342

Uncompetitive behavior: slope stays the same, but maximum velocity decreases.2345

Km decreases.2350

And mixed inhibition: slope changes, and Vmax changes.2353

Vmax ends up decreasing, but because the slope is changing, the Km actually increases; and that is what we are going to summarize right here.2357

You are going to be asked more than likely just to identify the behavior based on the Lineweaver-Burk plot.2366

We have our inhibitor.2375

We have our observed; and again, all of this is observed maximum velocity and observed Km.2380

This is what we actually measure when we say observed.2389

OK, now, when there is no inhibitor, your Vmax and your Km are exactly where they should be.2394

Now, for competitive inhibition, Vmax stays the same.2405

It does not change.2412

Your Km, that is, now, the observed Km.2417

It goes up; alpha is a number bigger than 1.2423

It goes up; uncompetitive behavior, uncompetitive competition, I am sorry.2427

Uncompetitive competition, yes, that makes sense- uncompetitive inhibition.2436

There, now, your Vmax is going to go down by a factor alpha prime, and your Km is also going to go down by a factor of alpha prime.2441

Alpha prime is bigger than 1, so both changes.2453

Mixed inhibition, your Vmax is still going to experience a decrease according to alpha prime.2458

Here is where it gets interesting; your Km, it depends on alpha and alpha prime.2473

This and this come together to form this, where alpha and alpha prime both show up.2483

If the inhibitor is behaving more as a competitive inhibitor or is displaying competitive inhibition, the alpha is going to be bigger than alpha prime.2500

You are going to end up with a Km increase; if alpha prime, if it is displaying more uncompetitive behavior than competitive behavior, you are going to end up with a slightly smaller Km.2507

This one is variable; this one depends on that.2520

Mixed inhibition, the alpha and the alpha prime both show up to affect the Km, to affect the amount of substrate concentration that will allow you to be at half maximum velocity- that is it.2524

Now, let's talk a little bit about...we will close it off with this discussion here.2540

Let me do that; OK, let me have another page- I do.2546

Notice, I am just going to mention non-competitive behavior.2551

I am not going to really talk too much about it, but I just want you to notice.2556

When alpha is equal to alpha prime, when the enzyme is displaying both competitive and uncompetitive behavior equally, in other words, when the equilibrium constants for the formation of enzyme inhibitor complex and enzyme substrate inhibitor complex, when that equilibrium is the same, alpha and alpha prime are the same.2560

When alpha equals alpha prime, that is when...remember what the definitions 1 plus the inhibitor com...over the equilibrium constant for formation of the enzyme inhibitor complex.2588

When it equals the alpha prime, which is that over the formation of the enzyme substrate inhibitor complex, when those are equal, this goes away.2609

This goes away; the inhibitor, you end up with this equal to that.2628

What happens is the following, which is ki = ki.2634

In other words, the equilibrium constants are forming at the same rate, then, the alpha x Km/alpha prime, since they are the same, it just equals Km.2643

When alpha = alpha prime, when it displays both competitive and uncompetitive behavior at the same rate to the same degree, you would have something called non-competitive behavior.2658

OK, now, we call it non-competitive.2668

In this particular case, the Km does not change; the Vmax changes- that is it, non-competitive inhibition.2679

You do not really have to know anything about non-competitive inhibition; you just need to recognize that it is when alpha = alpha prime or when competitive and uncompetitive behavior are operating to the same degree- that is it.2686

You do not really see it in practice; you probably never see it.2700

OK, now, let's go ahead and close it off with a quick discussion of irreversible inhibition.2705

I am just going to tell you what it is, give you an example, and then, we will leave it at that, so irreversible inhibition.2711

We have talked about reversible inhibition; irreversible inhibition is exactly what you think it is.2718

It is when you permanently disable the enzyme; there is no way for it to, sort of, recover.2726

OK, an irreversible inhibitor is one that binds covalently to the enzyme active site or elsewhere.2732

I will just put "elsewhere" just in case because you can have some covalent binding at some other site on the enzyme, which permanently deforms the enzyme, walks it into a shape where it can no longer do what it does.2757

So, that is still irreversible inhibition, and that is it; it is locked in that way.2768

It is never going to break free to become some functioning enzyme again.2772

The body has to create the enzyme again if it wants to do what it wants to do; so, one that binds covalently to the enzyme active site or elsewhere and permanently cripples the enzyme- that is it.2777

Now, the penicillins that you take as antibiotics, those are irreversible inhibitors of the bacterial enzyme transpeptidase.2799

Let's go ahead and take a look here; I am not going to really do any diagrams or anything.2811

I am just going to tell you a little bit about them; the penicillins are irreversible inhibitors that bind - the actual penicillin molecule - to bacterial transpeptidase enzyme, and what they do is actually prevent the final cross-linking of amino acid chains in the formation of the bacterial wall/cell wall.2816

The bacterial wall is something called a peptidoglycan; it is a combination of amino acids and sugars.2891

That is all it is, and we will discuss peptidoglycans in a little bit later.2899

OK, let me go to last step here, last page.2917

Now, give you just a little bit more information because I think it is really, really, actually an exciting field.2922

Penicillin binds permanently to a serine hydroxyl in the active site, and it prevents D-alanine from binding at this point- that is it.2929

It binds to this serine residue in the active site.2969

What is supposed to happen is that this D-alanine is supposed to come in, bind to the enzyme, and then, some other amino acid, a glycine, is supposed to come and bind to the D-alanine and kick off the enzyme to release the enzyme again so that it can go and do what it does; and now, you have this chain linked to this chain, this glycine linked to the alanine.2973

Well, the penicillin gets in the way; it binds to the enzyme, and now, it just shuts the enzyme down.2994

Now, it is stuck in the active site; nothing can happen- that is it.3000

That is irreversible inhibition; in order for the bacteria to do what it does, it needs to remake more enzyme.3005

By that time, the immune system has already taken care of the bacterial wall because the bacterial wall, it is not strong the way it should be.3012

It becomes very vulnerable, very, very susceptible, and it is actually quite easy to kill.3021

It is when the bacterial wall is there that it becomes very, very difficult to do any damage to it.3026

At this point, cross-linking cannot take place leaving a vulnerable bacterial cell wall.3032

In the case of penicillin, a penicillin does not actually kill the bacteria.3066

What it does is it stops it in its tracks from becoming what it is supposed to become so that the immune system can come and take care of the rest.3070

It is called bacteriostatic instead of bactericidal.3077

A bactericidal antibiotic actually kills the bacteria; this is bacteriostatic.3081

It just stops it in its tracks and lets other things do what they are supposed to do.3085

OK, that is enzyme inhibition.3091

Thank you for joining us here at Educator.com; we will see you next time, bye-bye.3095

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