Sign In | Subscribe
Start learning today, and be successful in your academic & professional career. Start Today!
Loading video...
This is a quick preview of the lesson. For full access, please Log In or Sign up.
For more information, please see full course syllabus of Biochemistry
  • Discussion

  • Download Lecture Slides

  • Table of Contents

  • Transcription

  • Related Books & Services

Bookmark and Share
Lecture Comments (2)

1 answer

Last reply by: Professor Hovasapian
Tue Oct 29, 2013 5:35 PM

Post by Jennifer Parkinson on October 29, 2013

I can't tell you how much your lectures have helped me with my studies. I wish all lecturers explained things as well as you do! Thank you Professor H!

Amino Acid Catabolism

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
  • Amino Acid Catabolism 0:10
    • Common Amino Acids and 6 Major Products
    • Ketogenic Amino Acid
    • Glucogenic Amino Acid
    • Amino Acid Catabolism Diagram
    • Cofactors That Play a Role in Amino Acid Catabolism
    • Biotin
    • Tetrahydrofolate
    • S-Adenosylmethionine (AdoMet)
    • Tetrahydrobiopterin
    • S-Adenosylmethionine & Tetrahydrobiopterin Molecules
  • Catabolism of Phenylalanine 18:30
    • Reaction 1: Phenylalanine to Tyrosine
    • Reaction 2: Tyrosine to p-Hydroxyphenylpyruvate
    • Reaction 3: p-Hydroxyphenylpyruvate to Homogentisate
    • Reaction 4: Homogentisate to Maleylacetoacetate
    • Reaction 5: Maleylacetoacetate to Fumarylacetoacetate
    • Reaction 6: Fumarylacetoacetate to Fumarate & Succinyl-CoA
    • Reaction 7: Fate of Fumarate & Succinyl-CoA
  • Phenylalanine Hydroxylase 33:33
    • The Phenylalanine Hydroxylase Reaction
    • Mixed-Function Oxidases
    • When Phenylalanine Hydoxylase is Defective: Phenylketonuria (PKU)

Transcription: Amino Acid Catabolism

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

In today's lesson, we are going to be discussing amino acid catabolism, so let's just jump right on in.0004

OK, we know that we have about 20 common amino acids.0011

Now, all 20 of the pathways for amino acid catabolism, for breakdown, all converge to 6 major products.0025

All 20 pathways converge to only 6 major products.0036

When an amino acid breaks down, all those 20, there is only 1 of 6 things that it ultimately becomes, and all of them enter the citric acid cycle.0051

OK, we have alpha-ketoglutarate.0066

We have succinyl-CoA.0076

We have fumarate, and you will recognize these as citric acid cycle intermediates.0080

We have oxaloacetate.0085

We have pyruvate, and we have acetoacetyl-CoA, which actually goes on to become the ketone bodies- not a problem.0091

We will be looking at that in just a second.0105

Now, let's go ahead and define just a couple more terms associated with amino acid breakdown.0109

One of them is something called ketogenics; we refer to a ketogenic amino acid, those that are ketogenic, well, those that degrade or break down or catabolize, degrade to acetoacetyl-CoA because they can go on to form ketone bodies in the liver.0113

Remember when we discussed ketone bodies earlier - excuse me - in the liver?0157

Those are called ketogenic amino acids; they tend to ultimately produce ketone bodies, and then, we have the glucogenic, and it is exactly what you think.0165

The glucogenic amino acids are those that degrade to oxaloacetate ultimately.0178

In other words, their final form will be oxaloacetate - OK - pyruvate or the other molecules mentioned above or the other molecules, which become oxaloacetate via the citric acid cycle because they go on to form glucose in gluconeogenesis- ketogenic amino acids, glucogenic amino acids.0194

OK, let's go ahead and take a look at a diagram of amino acid catabolism.0258

We will spend a couple of minutes on this, and just, sort of, get a sense of what is going on.0265

Let's look at the legend here; these amino acids are listed around here, and as you see, this is the citric acid cycle.0270

Here is oxaloacetate, citrate, isocitrate, alpha-ketoglutarate, succinyl-CoA.0277

Back up here, here is where acetyl-CoA from pyruvate comes in to the citric acid cycle.0284

The amino acids that are in red, those are the glucogenic amino acids right here: arginine, proline, histidine, glutamine.0290

These go break down into this; this ultimately goes to oxaloacetate.0299

Oxaloacetate here can follow this path to become glucose- glucogenic, these others, glucogenic, glucogenic, glucogenic.0304

Notice the ones in purple, I am sorry, the ones in green, those are strictly ketogenic.0306

The leucine and the lysine are strictly ketogenic.0322

When they break down, they break down to acetoacetate, acetyl-CoA, and then, they will go on to form ketone bodies.0327

These are the ones that are strictly ketogenic.0340

Now, the ones in purple, they are both glucogenic and ketogenic- the phenylalanine, tyrosine tryptophan.0344

Notice here, tyrosine, phenylalanine, phenylalanine is going to be the molecule that we are actually going to talk about specifically in a little bit.0351

We are going to follow its breakdown in detail- the isoleucine here.0359

Again, you can have amino acids that are both glucogenic and ketogenic.0366

This is a nice thing to just, sort of, try to wrap your mind around just to see where things are going.0372

And again, you have your fundamental molecules that you are breaking down into the alpha-ketoglutarate.0377

The succinyl-CoA, the fumarate, oxaloacetate, these break down into pyruvate.0383

These will break down into acetoacetate- that is it.0390

This is just a centralized picture of amino acid catabolism.0394

OK, now, before we discuss the breakdown of actually 1 or 2 of these amino acids, I wanted to look at some of the enzyme cofactors that are involved in amino acid catabolism - OK - specifically the 1-carbon transfers.0398

Let's go ahead and list some of these; let me go ahead and stay with red: cofactors that play a role in amino acid catabolism.0416

OK, there is biotin; we have come across biotin before.0445

There is tetrahydrofolate - OK - H4-folate.0450

You will often see it abbreviated that way, and there is S-adenosyl methionine.0460

OK, again, these cofactors, they are involved in the transfer of 1 carbon groups, but the carbons are in different oxidation states.0474

These cofactors, they transfer 1 carbon groups in different - well, let me actually write it over here - oxidation states.0487

OK, let's take a look at biotin here; let me go back to black, I think.0521

Biotin, we have already seen this; it transfers CO2 groups between molecules.0527

In this particular case, you have a +4 oxidation state.0537

OK, and if you remember right, there are different ways to consider oxidation state for a carbon.0548

What I call a +4 oxidation state - we talked about oxidation state back when we were discussing bioenergetics - other books might call it +8 oxidation state.0555

It just depends on when they start; some people go from 0 to 8.0568

Some people go from -4 to 4; there might be some other systems.0572

Just make sure that there is a consistency; it is not necessarily that this number is incorrect or another one is correct.0576

It is just a question of your point of reference; is your point of reference going to be 0 or is it going to be -4, depending on how you are assigning oxidation states.0582

Now, regarding biotin, recall the pyruvate carboxylase reaction.0593

This was one of the cofactors in the pyruvate carboxylase enzyme, which transfers CO2 from bicarbonate to pyruvate to form the oxaloacetate.0605

We have seen this before.0639

We have seen biotin before; now, tetrahydrofolate - OK, very, very, very important cofactor - it transfers 1 carbon groups in intermediate oxidation states.0643

An example might transfer this group, or it might transfer this group.0683

C, let's go ahead and write a double bond there, H, H- something like that, less than 4, greater than -4.0692

The intermediate oxidation states carbon fully oxidized +4, it has lost 4 electrons.0705

Carbon fully reduced like methane, it has 4 hydrogen atoms, it is in a -4 oxidation state.0712

The intermediate oxidation states some of those molecules, it is the tetrahydrofolate that facilitates that 1-carbon transfer for whatever particular enzyme happens to be under discussion.0720

Now, tetrahydrofolate, we will mention as a note, it occasionally transfers a methyl group, and a methyl group is the CH3.0732

It, occasionally, will transfer that, but most of the time no.0752

Most of the time, it is going to be the next cofactor - the S-adenosyl methionine - that does most of the transfer of methyl groups.0756

Let's go back to black here; S-adenosyl methionine, otherwise known as AdoMet, this one transfers methyl groups.0764

Excuse me.0784

This one is the one that transfers methyl groups, and there is 1 more, 1 additional cofactor.0789

It is not involved in the transfer of carbon groups; it is actually involved in oxidations, but it does play a role in amino acid catabolism, and in fact, it is going to be one of the cofactors that we see when we discuss phenylalanine in just a minute.0799

It is called tetrahydrobiopterin.0813

OK, you know what, let's try this again, shall we?0826

I am going to call it H4-biopaterine, so the tetra hydro- 4 hydrogens.0835

It is involved in oxidations.0845

OK, let's see if we can see a couple of images of some of these cofactors just to get a sense of it.0853

Biotin, we have actually dealt with before, and tetrahydrofolate.0860

Let's go ahead and take a look at S-adenosyl methionine and the tetrahydrobiopterin.0865

You know what, I think I am going to actually write this out.0873

Tetra hydro, there, how is that?0877

OK, the S-adenosyl methionine, this is your AdoMet molecule.0882

All of the chemistry takes place right here, around this S.0889

Notice this S has a positive charge; this single line here, there is this CH3 group right here.0893

Because this CH3 is attached to a sulfur atom, which is electron negative, these electrons really want to be there.0902

It makes this a really, really, really good methylating agent, an agent that puts a methyl group onto another molecule, a nucleophile.0909

If you have some nucleophile, some molecule, some substrate of the particular enzyme, I will just go ahead and call it...let me go ahead and do it in red.0918

If I have some nucleophile - OK - it is going to attack here, and it is going to push the electrons onto that.0933

That is what makes this a very powerful methylating agent.0940

If we need to transfer a methyl group, put a methyl group onto a is funny I have never really liked the word "transfer a methyl group".0945

I guess, mostly, it is just a question of your perspective, your point of reference.0954

If we are considering a particular substrate molecule, I have always thought about it as putting a methyl group on that molecule, not necessarily a transfer.0959

A transfer implies a certain equality between 1 molecule and the other, but if it is a particular molecule that you are concerned with, it is just going to be a nucleophile.0967

This nucleophile is the one that attacks the AdoMet, but really, what we are doing is we are just putting this methyl group on the nucleophile.0977

That is ultimately what is happening; in any case, it is up to you how you want to think about it, if you like the word transfer or if you want to think about it as some nucleophilic attack.0983

Ultimately, it is just a question of moving a methyl group from 1 molecule to the other.0993

All of the chemistry takes place there, and this just happens to be a picture of the tetrahydrobiopterin, just thought you should take a look at it- that is about all.0998

The tetra hydro part comes from 1, 2.1007

There is a hydrogen here; there is a hydrogen here.1013

That is where the tetra hydro part comes from- that is all.1015

And it is the same with tetrahydrofolate.1021

It is these 4 hydrogens that are here as opposed to dihydrofolate.1025

2 of the hydrogens are actually pulled away; it becomes oxidized and reduced back and forth.1028

That is what happens to it; OK, now, let's go ahead and follow the catabolism of phenylalanine.1035

I think I am going to do this in black.1043

Now, let's follow in detail the catabolism of phenylalanine.1047

OK, now, recall that phenylalanine is both keto and glucogenic.1070

Its breakdown products go on to form glucose possibly, and they can also go on to form keto bodies in the liver.1078

Recall that phenylalanine is both gluco and ketogenic.1085

Now, let's start; I think I am actually going to start on the next page so that I can do the molecule.1106

OK, I will start over there; alright, let's go ahead and draw this out, and we are going to actually list out some of the carbons that are important because we want to keep track of the carbons, so that, that, that, C, C, C, there, there, there.1111

This is going to be C, C, COO-, and we have NH3+.1128

This is our phenylalanine, and I am going to go ahead and mark off 1, 2, 3, 4.1136

Those are going to be the carbons that we want to keep our eye on.1143

1, 2, 3, 4, let me go back to black.1148

OK, now, our first reaction is...let me...slightly longer arrow here that I think I am going to need.1152

Let's go this way, and we are going to have O2 coming in.1159

We are going to have H2O coming out, and we are also going to have NADH + H+; and we are going to have NAD+, and this is going to be...the tetrahydrobiopterin is going to be the cofactor that is involved in this particular step.1165

I will write that as H - actually, I am going to do the enzyme in blue - H4-biopaterine.1186

That is the cofactor in the enzyme, is phenylalanine hydroxylase.1199

That is the first step, and what phenylalanine hydroxylase does is convert it into this molecule, converts it into tyrosine basically- another amino acid.1211

It basically adds a hydroxyl group.1223

Actually, it puts an OH group right there, so C, C, COO-.1228

This is our amino acid; this is the alpha-carbon.1237

Here is the amino group, NH3+; here is our phenylalanine up here, and the first step is the conversion to tyrosine.1241

OK, now, when there is a problem, when there is a genetic defect in this enzyme, the phenylalanine hydroxylase, that is the cause of the disease phenylketonuria.1257

I am going to go ahead over here in blue; actually, I will just leave it in red.1271

I will write PKU.1280

There are several genetic diseases along this pathway; if there are problems with these particular enzymes, it is the cause of that particular disease.1285

Let's go ahead and go back to black; OK, now that we have tyrosine, the next step in the breakdown is the following.1294

Let me go ahead and do a little arrow here; we are going to have alpha-ketoglutarate, and we are going to have glutamate, and the enzyme is going to be tyrosine aminotransferase.1301

We have seen aminotransferases before; they basically just transfer amino groups from 1 thing to another.1323

This amino group is going to go from this tyrosine; it is going to end up on alpha-ketoglutarate to turn it into the amino acid glutamate, tyrosine amino transferase, and what we end up with is the following molecule.1329

This part stays; no worries there.1348

This is OH; this is C.1354

Now, instead of the amino group, we have a carbonyl group.1357

We have C; this is OO-.1362

This is para-hydroxyphenylpyruvate.1364

This is guys should be familiar with this, para-hydroxy, para, meta, ortho, para-hydroxyphenylpyruvate.1368

OK, that is the next step in the breakdown of phenylalanine, so phenylalanine to tyrosine, tyrosine to para-hydroxyphenylpyruvate.1389

Alright, let's go ahead and see what the next breakdown is going to be.1398

Let's redraw this molecule up here: boom, boom, boom, C, C.1404

Let's put that there: C, C, and COO-.1412

This was our para-hydroxyphenylpyruvate.1420

The next step is going to be...O2 is going to come in.1430

CO2 is going to leave; the enzyme that is going to be responsible for this is para-hydroxyphenylpyruvate dioxygenase.1435

Para-hydroxy - woo, these names are just crazy - phenylpyruvate dioxygenase.1446

And again, it is going to depend on your particular teacher if they want you to know the enzymes or not know the enzymes.1455

OK, what this one does is the following; it converts it into this molecule.1468

OK, let's go ahead and draw this one out; we would draw this one a little bit differently, so 1, 2, 3.1474

I will put the C there.1480

I will put that, that, that, OH, OH.1486

This is going to be C.1493

It is going to be COO-; OK, I had 1, 2, 3, 4.1498

That was the 1, 2, 3, 4 carbon; now, these carbons, there has been a little bit of a shift, little bit of a move-around, little bit of a twist.1510

This is 1; this is 2.1517

This is 3, and that is the 4 carbon, now.1520

OK, these carbons are now these carbons.1524

OK, the name for this: homogentisate or homogentisate- depending if you want to pronounce it hard or soft.1528

It is totally up to you; OK, now, let's see what we can do to this one.1539

From here, we have O2, H+.1546

OK, we have homogentisate 1,2-dioxygenase, and you end up with the following molecule.1567

Let me write this out; I am actually going to do this one in blue: 1, 2, 3, 4.1583

And then, I am going to have my 1, 2, 3 and 4.1592

Let me see, 1, 2, 3, 4; this is my no. 1 carbon.1597

I have a carbonyl on no. 2, and, of course, I have a carboxyl over there.1601

This is my no. 1, so I have got a carbonyl over here.1607

I have a double bond over here, and I have a cis configuration on this one and a carboxyl over here.1611

This is maleylacetoacetate.1619

Let me mark off 1, 2, 3, 4, 1, 2, 3, 4.1623

We are going to break that one; this is our 1 carbon, our 2 carbon, our 3 carbon, our 4 carbon.1630

We want to keep track of the carbons to see what is going to give rise to what particular molecule.1636

OK, this is maleylacetoacetate.1640

OK, now, let's go ahead and redraw this molecule.1652

Let's go 1, 2, 3, 4, 1, 2, 3, 4, 1, 2, 3, 4.1661

This is our 1-carbon, so we have got a carbonyl over here, a carbonyl over here, a carboxyl.1671

We have a double bond here; we have that, and this is important because that is going to be a cis configuration right there.1677

In a minute, it is actually going to become a trans configuration.1686

It is going to become our fumaryl.1690

This is our maleylacetoacetate, and now, the transformation that takes place is going to be...everything is going to stay the same.1694

Let me mark my carbons again; this is going to be the 1, the 2, the 3, the 4 carbon.1712

Everything is going to stay the same, except this cis configuration on the alkene is going to be a trans configuration.1717

Now, what we have is the following.1722

Let's do 1, 2, 3 and 4, 1, 2, 3 and 4.1726

This is the no. 1 carbon, so I have got a carbonyl there.1737

I have got a carbonyl here, double bond; I am going to leave this one down below.1741

I am going to move this one up top, this OO- there, OO- here- there we go.1745

Now, we have fumaryl or fumaryl - depending on how you want to pronounce it - acetoacetate.1753

You can see where we are going to be going from here; we are going to end up splitting this molecule up into a fumarate and an acetoacetate- that is it.1760

That is all we are going to end up doing here; let me go ahead and write the enzyme that is responsible for this.1768

It is blue; it is maleylacetoacetate isomerase or isomerase.1775

It does not really matter; OK, now, let's go ahead and make our final products here.1790

Basically, water is going to come in, and it is going to split.1798

So, we have 1, 2, 3, 4; let's go ahead and break this particular bond right here, and we are going to create the following.1802

We are going to create fumarate.1808

Actually, you know what, I will just do this in blue for the fumarate, so 1, 2, 3, 4.1814

Let me go ahead and wait a minute, 1, 2.1824

Wait, yes, that is fine.1829

OK, I have got that; I have got that.1836

I have got that, and I have got that.1841

I have got this, and let me see.1848

I have got plus; now, let me go ahead and do this one in red.1853

This is going to be C, COO, C.1858

Let me see if I have got this right here.1865

It is going to be...yes, that is right, C and then COO-.1869

OK, here, we have our acetoacetate, and here we have our fumarate.1875

This fumarate here, this is going to go on into the citric acid cycle.1883

This is the part that makes it phenylalanine glucogenic.1898

This one is going to do the following, do it in red.1903

What this one is going to do...actually we will keep it in blue; that is fine.1909

We have succinyl-CoA.1914

We have succinate, and we are going to end up with our...let me do this in red.1923

We are going to be C, C, C, C, S-CoA.1935

The coenzyme A is going to be transferred from the succinyl-CoA to this acetoacetate.1941

It is going to become acetoacetyl-CoA.1947

Let me go ahead and finish off with the carbonyls here; I will go ahead and put the hydrogens here.1951

I will go ahead and put an H there, put an H there.1958

This one, it ends up either becoming acetyl-CoA and entering the citric acid cycle - this is one possibility this way - or it could go on to form ketone bodies.1961

This particular molecule can go in either direction.1975

The phenylalanine breaks down through his process, breaks down into acetoacetate and fumarate.1980

Fumarate will go on to the citric acid cycle, and then, the acetoacetate can either go on and become acetyl-CoA, which will enter the citric acid cycle, or it will go on to the liver and form ketone bodies- glucogenic, gluco, ketogenic.1989

OK, now, let's actually go back and talk about what happens in the first step, the phenylalanine hydroxylase reaction.2007

I just wanted to talk a little bit about the cofactor, the biopterin, the tetrahydrobiopterin.2017

OK, let's take a look at that again.2023

We are going to look a little bit more at the phenylalanine hydroxylase reaction, which is the first step of the breakdown.2028

That was reaction no. 1; OK, the reaction that we had was the following.2044

We had phenylalanine; I am not going to go ahead and draw these out again.2050

I am just going to write what is going on actually; let me give myself a little bit more room here.2053

OK, that was where it went from phenylalanine to tyrosine.2070

We had O2 coming in; we had H2O leaving.2075

We had NADH+ leaving to form NADH + H+, and this is the enzyme.2083

I will not list the enzyme; the enzyme is the phenylalanine hydroxylase.2095

The cofactor was the H4-biopterin.2100

Let me do it in blue; this was the cofactor.2106

We had the tetrahydrobiopterin, H4-biopterin.2109

That was the cofactor; here is what happens in this particular reaction.2116

Watch this: 5, 6, 7, 8 - OK - tetrahydrobiopterin.2123

Four hydrogens goes to 7,8-dihydrobiopaterin2137

OK, what we have is the phenylalanine.2157

Actually, you know what, I think I want to draw this one out; I am sorry.2168

I think I want to draw this one out, so I am going to actually move a couple of things around here.2172

I am going to give myself a little bit more room on the sides, so 5, 6, 7, 8 tetrahydrobiopterin goes to 7,8-dihydrobiopaterin.2179

OK, we have our phenylalanine; it is going to look like this: boom, boom, boom, boom, boom, boom, boom, C, C, COO-, NH3+.2210

I am actually going to show that particular H.2225

This is the actual reaction that takes place here; this is the O2.2229

This is the O2, and this is where the enzyme is; this is the phenylalanine hydroxylase reaction.2233

Well, I will not actually list it; the reaction that is taking place is taking place right here.2238

It is phenylalanine being converted to tyrosine.2243

I will go ahead and draw this out again; what is going to be interesting, I will write this H.2248

I will write that C, C, COO-.2254

OK, here is what is interesting about this particular reaction.2261

I specifically drew this H; that H is that H.2265

The phenylalanine hydroxylase, what it does, it attaches a hydroxy to this carbon right here, but what it does is it actually shifts.2270

It moves this particular hydrogen down one; it moves it here.2277

This is called the NIH shift- National Institute of Health; that is where it was discovered.2281

Now, let me go ahead and finish this, sort of, cyclical thing here.2287

Let me go to blue, and then, we have NADH + H+ goes to NAD+; and this particular enzyme over here is called dihydrobiopterin reductase- exactly what you think.2293

What is mentioned here, O2 coming in, H2O leaving, NADH + H+ coming in, NAD+ leaving, the actual reaction that takes place, here is the sequence.2327

This 5, 6, 7, 8 tetrahydrobiopterin, there are 4 hydrogens on this biopterin cofactor.2337

What it does is it transfers the phenylalanine hydroxylase.2344

It uses O2; OK, it attaches one of the oxygens with a hydrogen to this.2350

The other oxygen atom of the O2, it ends up reducing it to water.2357

It converts phenylalanine to tyrosine, and the process of giving up 2 of its hydrogens from 5, 6, 7, 8 tetrahydrobiopterin, it becomes 7,8-dihydrobiopaterin.2361

Now, in order to get back to its original form so that it can continue the catalytic cycle, it uses NADH.2373

OK, now, the NADH reduces the 7,8-dihydrobiopaterin to the 5, 6, 7, 8 tetrahydrobiopterin, and it is converted to NAD+.2382

Everything that you see here, this is the entire process; this is absolutely beautiful.2393

This goes here, turns into this; it uses something else to reduce so it can continue the cycle- absolutely fantastic.2397

That is what is happening in this particular reaction, the first reaction of the breakdown of the phenylalanine.2404

OK, and again, notice that the para, H, has now moved to the meta position.2412

OK, this hydrogen is this hydrogen.2416

It is not some random hydrogen; it actually moves down.2420

OK, final couple of words here about phenylalanine or actually the enzyme itself, let's go stick with blue.2425

Phenylalanine hydroxylase - OK - is one of a class of enzymes called mixed function oxidases or monooxygenases.2436

Again, with enzymes, you are going to have different names for them.2486

An oxidoreductase, we tend to call it by its more common name a dehydrogenase.2490

A monooxygenase is a more formal name; we call it a mixed function oxidase.2497

That is going to be...well, that is a really, really annoying part about biochemistry, is that multiple names for the same concept of the same enzyme especially with enzymes shows up.2502

Unfortunately, you are going to have to be aware of both; sorry.2514

OK, phenylalanine hydroxylase is one of a class of enzymes called mixed function oxidases or monooxygenases.2520

Now, what they do, they all catalyze the same thing.2527

They all catalyze the hydroxylation - like we just saw - of a substrate.2531

In other words, they attach an OH group to some carbon on the substrate.2546

They all catalyze the hydroxylation of a substrate by one of the O atoms/oxygen atoms of O2, and the other oxygen atom is reduced to water.2553

It is always going to be O2 that comes in; one atom is attached to the substrate.2583

The other is reduced to water.2590

OK, OK, now, and, of course, this particular enzyme happens to require tetrahydrobiopterin as a cofactor.2595

That is not true of all of the mixed function oxidases.2605

This one happens to require that.2609

Now, we said earlier that when phenylalanine is defective, the individual suffers from something called PKU - phenylketonuria - where phenylalanine does not follow because it cannot go through that first step of the reaction, the phenylalanine hydroxylase reaction.2613

It takes an alternative pathway for its breakdown, and it does not follow the normal degradation; but what it does is it actually exchanges its amino group with pyruvate to become phenylpyruvate, and when phenylpyruvate builds up, that is what causes the particular disease PKU.2630

Let me go ahead and just write that down really quickly, and we will finish off with that.2648

Let me go back to black; now, when phenylalanine hydroxylase is defective, the individual suffers from PKU - phenylketonuria - where phenylalanine degrades by an alternate pathway.2655

Actually, it does not really degrade; it just converts to 1 product, and that product builds up.2704

What happens is the following; I wonder if I should do it on...that is OK.2709

I guess I can do it on this page; what we have is...let's go ahead and go back to blue here.2713

We have our phenylalanine, C, C, COO-, NH3+.2720

What ends up happening is C, C, COO.2729

It ends up transferring this amino group to pyruvate.2738

The pyruvate end up turning into this, and this ends up becoming - O- - phenylpyruvate.2744

This is the phenylalanine, and this is the phenylpyruvate, which accumulates and is the cause of lots of trouble.2767

When the phenylalanine hydroxylase is defective, it takes this particular pathway, and it is the cause of PKU.2782

OK, now, in this particular lesson, in the beginning, we looked at, of course, that diagram that described the breakdown of all of the 20 common amino acids.2791

We have only looked at the specific breakdown, the details of 1 of these, the phenylalanine.2801

I urge you very, very strongly, to take a look at, at the very least, the breakdown of 2 or 3 of the other amino acids.2806

You can choose whichever ones you want; perhaps your teacher will give you a list of specific amino acids that you have to know the details of.2818

Perhaps not, but again, the idea is do not necessarily have to write these down in their active form, but you should be able to follow the breakdown.2827

That is the whole idea; you want to be able to look at a particular pathway and be able to follow what is going on, not necessarily mechanistically.2839

It just depends on what it is that you have to know for your exams, but just to get a sense of the patterns that are available in all of these pathways.2846

Now, of course, each individual amino acid will break down in a different way as far as the details are concerned, but it is good to get a sense of the patterns.2856

So, I strongly urge you to take a look at, at the very least, 2 or 3 other amino acids, and just follow the path.2864

It is available in your biochemistry books.2871

Thank you for joining us here at and Biochemistry.2874

We will see you next time, bye-bye.2878