Amino acid metabolism and catabolism
How that catabolism allows us to produce ATP inside ourselves is unclear. Now, compared to carbohydrate catabolism and fatty acid catabolism, recall the pathways of glycolysis and fatty acid oxidation. Compared to those pathways, amino acid metabolism only accounts for about 10 to 15% of our total energy production.
So that's why I think that amino acid metabolism doesn't usually get its fair share of airtime compared to processes like glycolysis and fatty acid oxidation. And to do that, let's go ahead and follow what happens to amino acids in the fed state as well as the fasted state of our body. Now, "fed" refers to our body's state right after, immediately after eating a meal. In terms of hormones, the hormone that's going to be elevated is going to be insulin, which is elevated in response to higher blood glucose levels immediately following a meal, and levels of the hormone glucagon are going to be decreased. Of course, this is going to be the opposite several hours after a meal, which we call the fasted state, in which the levels of insulin will be decreased. And, of course, in response to low blood glucose levels, the levels of glucagon in our body will start to rise, along with a couple of other hormones as well. But these are the two, or two at least, big hormones that regulate the bulk of the metabolism in our bodies.
We ingest proteins from our food, and those proteins are broken down into amino acids inside our small intestine. You might hear the terms "essential" and "non-essential" amino acids used, especially in the medical literature. And what this simply refers to is that essential amino acids are those amino acids, of the 20 that we know of, that our body cannot synthesize and so we must, somehow, get them in our diet. Whereas non-essential amino acids can be synthesized in our body, we don't need them as part of our diet. But, getting back to these amino acids, once they're broken down in the small intestine, they travel via the bloodstream directly to the liver, just like glucose.
Once the amino acids have made it to the liver, several things can happen. The liver can use these amino acids directly for protein synthesis. But it can also use any excess amino acids and convert them into glucose and fatty acids. In both cases, the ultimate storage forms of these two molecules are going to be glycogen, in the case of glucose, which is stored in the liver mainly, and fatty acids, we store these as triacylglycerides in our adipose tissue.
This conversion from amino acids to glucose and fatty acids happens. The precursor for glucose can be pyruvate as well as oxaloacetate. And, for fatty acids, the main precursor for fatty acid synthesis is the molecule acetyl-CoA. And, the acetyl-CoA happens to be in equilibrium with another molecule in the cell called acetoacetyl-CoA. and oxaloacetate. In equilibrium with a lot of the intermediates of the Krebs cycle, There are numerous molecules with numerous names, but just so that you get the big picture. Now, the key point here is that amino acids, specifically the carbon backbone of these amino acid molecules, can be interconverted and metabolized directly into the molecules in the precursor molecules.
So they can be converted directly into pyruvate, oxaloacetate, as well as intermediates of the Krebs cycle, acetyl-CoA, as well as acetoacetyl-CoA. Now another classification that you might hear with regard to amino acids is whether an amino acid is called a ketogenic amino acid or whether it is a glucogenic amino acid, and that simply refers to whether the carbon backbone of these amino acid molecules feeds into the precursor molecules for glucose synthesis or whether it feeds into the precursor molecules for fatty acid synthesis. So, in this case, ketogenic amino acids are converted to acetyl-CoA or acetoacetyl-CoA and ultimately fatty acids, whereas glucogenic amino acids feed into pyruvate, oxaloacetate, or intermediates of the Krebs cycle.
Now, just as a fun fact, it turns out that there are two amino acids that are exclusively ketogenic, and those are lysine and leucine. So anytime you ingest lysine or leucine, you will definitely be making fatty acids from those amino acids if they're ingested in excess. Other amino acids can actually contribute to glucogenic pathways, and some might even contribute to both. Going back to our amino acids here, the liver can either use them for protein synthesis or convert them into other energy storage forms. But it can also send it off, and it can send it off to other tissues such as the muscle, for example, where the muscle can use it for its own protein synthesis. So other cells will also receive amino acids that are digested that they can use for protein synthesis as well. Moving on to the fasted state, the liver is quite a centerpiece when it comes to metabolism. A lot of things are going on in the liver, and, specifically, in the fasted state, the fatty acids are being released from adipose tissue and being sent to the liver where they're being oxidized, and all of that ATP is fueling the synthesis of glucose. And if the person is in a very severe state of starvation, meaning they haven't had a meal for two or three days, we might even be producing ketones as well. Even though we think of fatty acids as being the main fuel that's being sent to the liver in times of fasting, we can't forget about amino acids, which are released from our tissues and are sent via the bloodstream to the liver. Once amino acids have arrived at the liver, the factory house for energy production in times of fasting, they can enter a diverse array of metabolic pathways.
In times of fasting, potentially, these glucogenic amino acids can contribute to these precursors of gluconeogenesis and help support the production of glucose in times of fasting. Now those that become intermediates in the Krebs cycle might potentially also contribute to the production of some ATP in the cell, but only about 10 to 15% of our total energy production is supplied by amino acids, so we still think about fatty acids comprising the bulk of ATP production inside our body, but these amino acids are clearly important for providing those carbon backbones to support glucose synthesis.
These ketogenic amino acids could also potentially contribute to the synthesis of acetyl-CoA and, subsequently, ketones, but the whole purpose of ketone synthesis was to try and preserve the degradation of protein in our muscles so that we could switch to a more sustainable fuel based on the immense influx of fatty acids that we were getting into the liver. So really, this acetyl-CoA that contributes to ketone synthesis is largely coming from these fatty acids, so I'll go ahead and kind of write this double arrow in to remind us of that fact.
Catabolism of amino acids
At the basic structure of an amino acid at physiological pH, we know that we have this carboxylate anion, and we have this carbon here attached to an amino group that's protonated. And we also have some type of functional group, which we usually abbreviate as "R," which makes the identity of all these amino acids unique, and then we can't forget this extra hydrogen here. So that's the basic structure of an amino acid. The breakdown of proteins that we haven't run into in the breakdown of fatty acids or glucose is the presence of this nitrogen in this amine group.
Now, notably, this amine group was contributing in any way to these precursor molecules that we talked about above with regard to the breakdown of amino acids, and specifically, I used the term "carbon backbone of amino acids" to refer to this part right here that was being converted into all of these precursor molecules. And indeed, generally, the first step involved in the catabolism of amino acids or the breakdown of amino acids is something called a transamination step, in which the amine group of this amino acid is transferred to another molecule for eventual excretion by the body, and that frees up the carbon backbone to contribute to the rest of these metabolic pathways. And so ultimately, this becomes something called an alpha-keto acid, and it's called an alpha-keto acid because of what its structure looks like, so it ends up looking something like this. It obtains a ketone group here and is still attached to its R group. So it's alpha because it refers to this alpha carbon relative to this carboxylate ion, and it's a keto because it's a ketone, and it's an acid because it's attached to this carboxylic acid functional group here. So alpha-keto acid is the carbon backbone that can contribute to all of those metabolic pathways. The common acceptor for this amine group, the common molecule that accepts this amine group from amino acids, is a molecule called alpha-ketoglutarate. And this might ring a bell because it is an intermediate in the Krebs cycle, and when it accepts this amine group, it becomes a molecule of the amino acid glutamate. And then finally, what glutamate does is that once it reaches the liver because the liver happens to have the right types of enzymes for this next process, it can donate this amine group in the form of ammonia, which is NH3, and in equilibrium with ammonium, NH4 plus. It will donate this as ammonia, and this will enter something called the urea cycle inside the liver, where this ammonia is converted to a molecule of urea. This urea is then excreted in your urine, so that's how our body is able to effectively use the carbon backbone of these amino acids and also essentially detoxify our body of this nitrogen-containing amine compound. It's so important for you to eventually excrete this compound from our bodies because ammonia is toxic at very high levels in our bodies. So we need a way to get it out of our bodies, and this is how our bodies do it.
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