Once proteins are broken down into their individual amino acid constituents, what happens to those amino acids next? What is the fate of amino acids once proteins are actually degraded? Well, for the most part, the amino acids can be used in bisynthetic processes to form new molecules.
For example, we can use amino acids to build proteins, we can use amino acids to build nucleotide bases. But let's suppose... we have all the proteins that we want and we have all the nucleotide bases that our cells can actually use. What happens to any extra leftover amino acids?
Well you might be thinking we can store those amino acids for later use. So in the same way that we can store glucose as glycogen and we can store extra fatty acids as triglycerides, can we store extra amino acids inside our cells? And the answer is simply no. our cells do not have a way to actually store any excess amino acids. And so what must happen to these extra amino acids is they must be broken down.
Now the majority of the breakdown of amino acids occurs inside our liver, but other cells, just muscle cells, can also break down amino acids. For example, inside our muscle cell, we basically break down branched chain amino acids such as leucine, isoleucine. and Valine.
So let's take a look at how we actually break down amino acids. Now we have different ways by which we break down different amino acids, but let's begin by focusing on this two-step process here. So essentially the goal in the breakdown of amino acids is first we have to remove that amino group from that amino acid to form our ammonia The ammonium ultimately is fed into the urea cycle and that removes that ammonium from the body.
And the leftover carbon skeleton that we have, leftover after this process occurs, that is used to form energy molecules. And we'll talk about that in a lecture to come. So this is a two-step process by which first we take the amino acid, we undergo a transamination step in which we basically transfer this. green group onto a different molecule we form glutamate and in the second step we actually have that deamination step so we deaminate we remove the alpha amino group and we form the ammonium at which point this ammonium can now be fed into the urea cycle now let's begin by focusing on just on just this reaction here so we have transamination transamination is catalyzed by an enzyme known as aminotransferase and we also call it transaminase but in this lecture we're going to refer to it as simply aminotransferase.
Now aminotransferase, as we'll talk about in more detail in the next lecture, uses an important coenzyme a vitamin B6 derivative known as pyridoxal phosphate. So pyridoxal phosphate needs to be present for this enzyme to actually be effective. If we have deficiency in this coenzyme here, this enzyme will not function correctly. So this is a general process that takes place.
We begin with some target amino acid that we have too much of. So we wanna break this down. We reacted with an alpha-keto acid, and we basically form these two products here.
So we transfer this green group, the alpha-amino group, onto this group here, remove this oxygen, and we form these two molecules. So we form another amino acid, which is actually a glutamate, as we have in this diagram here, and we form this alpha-keto acid. Now, this molecule can basically be used for energy purposes, as we'll see in a future lecture. But this molecule must further undergo a process, the deamination step, to basically generate that free ammonium.
So let's look at two examples of these processes. So we have different aminotransferases, and two common examples are alanine and aspartate aminotransferases. So as you might imagine, in this particular case...
the beginning amino acid is alanine, in this case it's aspartate. So in both cases the alpha-keto acid is alpha-ketoglutarate. So we use this molecule to basically transfer this green alpha amino group onto the alpha-ketoglutarate. Now when we remove the alpha amino group, this green group from alanine, we basically form pyruvate.
When we do the same thing for aspartate, we form oxaloacetate. Because these two molecules are exactly the same, when we transfer that green group onto alpha-ketoglutarate, we basically form the glutamate. And it's the glutamate that goes on to undergo the oxidative deamination step to basically abstract that ammonium, as we'll see in just a moment.
Now, the last thing I'd like to mention about this process is it goes both ways. So we can go this way. but we also go in reverse.
So this reaction actually exists in equilibrium. And why is that important? Well, it's important the following way.
So going this way, our cells can break down alanine and aspartate and other amino acids, but going in reverse, that actually gives us a way to form new amino acids. So we can begin with these molecules and go on to form alanine or aspartate if our cell actually needs to do that. Now, let's go on to step number two, so the oxidative deamination step.
So once we transfer that amino group from the target amino acid onto the alpha-ketoglutarate to form the glutamate, what is the fate of that glutamate? Well, what we want to do is we want to deaminate the glutamate, and this happens in a two-step process. So we have a dehydrogenation, and then we have this hydrolysis reaction.
Okay. So we take the glutamate and we basically want to remove this H here and this H here. We also want to remove two electrons.
And so we form a pi bond between this carbon and this nitrogen. And so this is actually an oxidation reaction reaction, oxidation reduction reaction. And so the molecule that we use as a coenzyme is NAD+.
Now, the enzyme that catalyzed this step. is no longer this enzyme, it's a different enzyme known as glutamate dehydrogenase. Now glutamate dehydrogenase is interesting because it not only uses NAD+, but it can also use, instead of the NAD+, NADP+.
So we can replace this with NADP+. But ultimately, we use this, or the enzyme uses this, to basically remove the two electrons and the H, which is the H. To form the NADH, we also remove the H+, and we form a double bond between carbon and the nitrogen, and we form this shift-based intermediate shown here.
Now, in the second step, we actually have the deamination step, or we can also see it as a hydrolysis step, because we use a water to basically hydrolyze and remove that ammonium. And so we replace the nitrogen, H2, with an oxygen, and we abstract. that ammonium. So we take the two H's from here and the two H's from the water and we form that ammonium.
And we also form the alpha-ketoglutarate as the final product. Now one interesting thing about glutamate dehydrogenase is that it is found in the mitochondria. Now why is that important? Well the final product form of this process is ammonium and ammonium is a very toxic substance. And so if ammonium was readily formed in the cytoplasm, that can actually damage the cell.
And so to prevent that from actually happening, our cell sequesters the glutamate dehydrogenase in the mitochondria, and it basically keeps that ammonium inside the mitochondria, preventing it from actually damaging the cell. Another important thing about this reaction is the same thing we mentioned here. These arrows go both ways and so we can basically go this way but if the conditions change we can also go this way. Now under normal conditions the reaction actually goes forward.
Why? Well because normally every time before the ammonium product that ammonium is used up in the urea cycle and so if we continually use up this violent product that will drive this reaction forward. So if we summarize these two reactions, the transamination and the oxidative deamination, we basically form this diagram here. So we begin with the target amino acid, and we have the alpha-ketoglutarate, as we saw in this particular case.
This is catalyzed by aminotransferase, and so we ultimately form aglutamate and the alpha-ketoacid, in this case pyruvate, in this case oxaloacetate. Now in the second step that is catalyzed by glutamate dehydrogenase, the glutamate reacts with the N-glycerin. NAD plus or NADP plus and water to basically form the alpha-ketoglutarate and that ammonia. And so this ammonia then goes into the urea cycle.
It is used up and so this reaction is driven in this direction. So we see that the majority of the amino acids inside our cells, more specifically our liver cells, hepatocytes, basically undergo this two-step process to deaminate that amino acid. Now other amino acids, such as serine and threonine, undergo other processes to basically deaminate it. So in this case, we have a two-step process that deaminates the amino acid. But for serine and threonine, this is a single step process and it's catalyzed by single enzyme, a dehydratase.
So we call it a dehydratase because there is a dehydration reaction that precedes a deamination reaction, as we'll see in just a moment. So for serine, we have serine dehydratase that basically deaminates the serine into pyruvate and that forms ammonium. For threonine, we form alpha-ketobutyrate and the ammonium.
The ammonium goes into the urea cycle. These can be used for energy purposes. Now to see exactly what happens, let's focus on this reaction here, reaction one.
So we begin with our serine, and this enzyme dehydratase basically allows it to undergo a dehydration step. And so what happens is this hydroxide group combines with an H-atom, this H-atom here, to basically form a double bond between this carbon, this carbon, and we form this high-energy intermediate molecule. Now, this high-energy intermediate molecule is unstable, and so it rarely converts into this final product, and this is our deamination step.
So this deamination step is similar to this one here because we also use water in this hydrolysis step. So we essentially allow... this group here to be kicked off, we form that ammonium and that ammonium then goes into the urea cycle.
So this is basically the process by which we deaminate amino acids and by deaminating the amino acids We basically form carbon skeletons and we form ammonium. The ammonium can be used in the urea cycle and that carbon skeleton can be used to basically form energy molecules, as we'll see in a future lecture. So we see that some of those amino acids are basically deaminated in a two-step process, in an indirect process. while other amino acids undergo this process in which we have a single-step process by which we deaminate that amino acid.