Amino Acid Metabolism

In my previous posts for this unit, I've spoken about the breakdown of fats and about the breakdown of carbohydrates, but I haven't spoken about the breakdown of amino acids. Well, now's the time!

Understand the concept of nitrogen balance.

Amino acids, true to their name, contain a nitrogen-containing amino group. As proteins are continually being broken down and recycled, some of the nitrogen has to be replaced every day. If our nitrogen intake is greater than our nitrogen excretion, we are said to be in positive nitrogen balance. Positive nitrogen balance is sometimes necessary for growth- in fact, foetuses and babies need more protein than adults for this reason. Conversely, if our nitrogen intake is less than our nitrogen excretion, we are said to be in negative nitrogen balance. Negative nitrogen balance may occur during muscle wasting.

Know the difference between ketogenic, glucogenic, essential and nonessential amino acids.

See earlier post: Metabolism of Protein and Carbohydrates

Describe the deamination and transamination reactions of amino acids in metabolism.

*Rolls up sleeves* Okay, let's get started on the meaty stuff!

First, let's talk about deamination, which is simply the removal of an amino group. Glutamate is kind of unique in that it's the only amino acid that has a specific dehydrogenase enzyme for it, and thus to my understanding it is the only one that uses this pathway. Glutamate dehydrogenase converts glutamate into α-ketoglutarate and ammonium ion. As mentioned here, α-ketoglutarate is a component of the citric acid cycle, so it can get converted into oxaloacetate and then into glucose, via the process of gluconeogenesis. As for the ammonium ion, it eventually gets converted into urea and excreted, but I'll get into that later.

Most other amino acids use transdeamination, or transferral of its amino group onto another molecule (usually α-ketoglutarate). The enzymes involved in transamination are known as transaminases or aminotransferases. No matter what you call them, though, they are all bound to pyridoxal-5-phosphate (PLP), which is a cofactor. For example, alanine and α-ketoglutarate can be converted into pyruvate and glutamate via the use of alanine aminotransferase. Fun fact: pyruvate is also known as an α-keto acid, which is a fancy way of saying "carbon backbone of an amino acid." Pyruvate can then do what it normally does (break down to lactate in the absence of oxygen, or enter the TCA cycle when there's oxygen around), whereas glutamate can be broken back down into α-ketoglutarate via the process of deamination, as I just described a paragraph ago.

Some amino acids have to do some unique stuff before they can undergo transdeamination. Serine can have its -OH group ripped off by serine dehydratase to form an amino-acrylic acid. In a similar vein, cysteine can also have its -SH group removed by cysteine desulfurase (the slides say "in bacteria," so I'm wondering whether this is done by gut bacteria or something) to form the same amino-acrylic acid. (Apparently the only difference between serine and cysteine is that one has an -OH where the other has -SH. Huh, didn't notice that before. I guess you learn something new every day.) Anyway, amino-acrylic acids can be converted into pyruvate and ammonium ion via an intermediate.

Phenylalanine is quite unique, in which it is normally converted into tyrosine first. The enzyme that converts phenylalanine into tyrosine is called phenylalanine hydroxylase, which is deficient in patients with phenylketonuria (PKU). In most people, this all goes well and then tyrosine can go on to form sugars or fats (it is both ketogenic and glucogenic). In patients with PKU, however, phenylalanine can undergo transamination to form phenylpyruvate, which is toxic.

Explain the various uses of amino acids. Know the processes of amino acid usage within the body.

Amino acids, as you should know by now, are the building blocks of proteins, but they can do more than that. As mentioned in an earlier post, glucogenic amino acids can be used to generate glucose, whereas ketogenic amino acids can be used to generate fats. The first step of this process is the breakdown of the amino acid into ammonia and a keto acid, which can then go on to either form a component of the TCA cycle (in the case of glucogenic amino acids) or acetyl CoA (in the case of ketogenic amino acids). In "maple syrup disease," the enzymes that assist in the conversion of valine, isoleucine and leucine into glucose and/or fat are defective.

Many other important biological molecules, such as neurotransmitters and catecholamines, can also be synthesised from amino acids. This process, however, requires initial decarboxylation (i.e. removal of the carboxylic acid group) of the amino acid. Methionine can also have a methyl group removed in order to form cysteine. These methyl groups can also go on to form important molecules, such as creatine and nucleic acids.

Have a basic understanding of the role and process of the urea cycle.

Before I get into discussing the urea cycle, I want to discuss ammonia, or rather ammonium ion, as that's normally the end result of process such as deamination of glutamate (see above). Ammonium ions, being toxic and all, can't be transported in the blood so they have to be bound to something first. There are a couple of mechanisms in which this can proceed:

In the first mechanism, glutamate (yup, this amino acid is really getting the limelight in this post) can combine with ammonium ion to form glutamine. Glutamine can be transported in the blood to the liver, where it can be broken back down into glutamate and ammonium ion by glutaminase.

In the second mechanism, amino acids such as alanine can undergo transamination in the liver, thereby pretty much bypassing the entire "how do we transport ammonium in the blood" problem. I'm not sure if this applies to amino acids other than alanine (and I'm too lazy to look that up), but that's the specific example given in the lecture slide.

Onwards to the urea cycle!

The urea cycle, as the name suggests, results in the production of urea from ammonia. Each turn of the urea cycle requires only 3ATP, so it is relatively energy-efficient. The first step involves carbon dioxide and ammonia reacting together to form carbamoyl phosphate, which then combines with L-ornithine to form citrulline, then argininosuccinate, then L-arginine and back to L-ornithine. In that final step (L-arginine -> L-ornithine), urea is released. (I'm not sure how much of this cycle we'll actually need to know.)