Amino Acid Metabolism

Hello :) In this post we'll be discussing the breakdown of amino acids in the body. We'll have a look at the fate of carbon skeletons which originate from amino acids as well as the disposal of nitrogen from amino acids through transamination and oxidative deamination. We'll also discuss the importance of urea as well as the function, location and regulation of the urea cycle. We'll finish off by talking about glutamine and the glucose/alanine cycle. Enjoy! :)

The Fate of Dietary Amino Acids

When the animal is consuming a high protein diet, a high amount of protein is present in the blood plasma. This leads to amino acid catabolising enzymes to break down amino acids. These enzymes have a high Michaelis constant (Km) and thus function at high protein concentrations. If the animal consumes a diet that is low in protein, then low protein concentrations will exist in the blood plasma. This causes Amino acyl-tRNA enzymes to start protein synthesis. These enzymes have a low Km and so function at low protein concentrations.

Amino acid catabolism occurs when the animal consumes a high protein diet or is starving. These scenarios all utilise deamination, the removal of the amine group from an amino acid, which leaves behind a carbon skeleton. In high protein diets this is used for energy and gluconeogenesis for glucose homeostasis. During starvation, the carbon skeleton is mainly used in gluconeogenesis to generate glucose, which is of course very important for a starving animal!

The Removal of Amino Nitrogen from Amino Acids

Amino Nitrogen (amino-N) can be removed from an amino acid through two different processes: transamination and direct deamination. Transamination occurs in all tissues but mainly in the liver and involves the alanaine, aspartate and glutamate transaminase enzymes. Direct deamination involves the glutamate dehydrogenase enzyme in the liver and the glutaminase enzyme in the liver and kidney.

Transamination

The three amino acids mentioned above function according to the following equations:

Alanine Transaminase:amino acid + pyruvate ⇌ keto acid + alanine
Glutamate Transaminase: amino acid + α-Ketoglutarate ↔ keto acid + glutamate
Aspartate Transaminase: amino acid + oxaloacetate ↔ keto acid + aspartate

As you can see, each reaction involves the swapping of the NH2 group from one molecule. For example, in the case of alanine transaminase, the amine group is transferred from the amino acid to the pyruvate producing a keto acid and alanine. 

Oxidative Deamination:

The deamination enzymes I mentioned earlier function according to the following equations:

Glutamate Dehydrogenase: L-Glutamate +   NAD+  → α-Ketoglutarate + NADH + H+   + NH3
Glutaminase: Glutamine + H2O → glutamate + NH3

In each case the amine group is completely removed, allowing the amino-N to be disposed of via the kidneys. 

The Urea Cycle

Ammonia (NH3) produced through amino acid catabolism needs to be removed from the bloodstream and cells because it is toxic to the nervous system. To do this, the body converts ammonia to urea which is synthesised in the liver, transported in the blood and excreted by the kidney into the urine. Importantly urea is non-toxic. 

The Structure of Urea

Urea is produced through the urea cycle which occurs in the liver, in both the mitochondria and cytosol. It is quite an energy-expensive pathway as it uses 4ATP molecules to produce one molecule of urea. This website has a good explanation of the urea cycle pathway. For our unit we don't need to know the pathway in great detail, just the location, function and regulation, but it is still useful to refer back to. 

Regulation

The enzymes involved in the urea cycle are induced (their activity increases by 20-fold) by a high protein diet or starvation. In addition, the enzyme carbonyl phosphate synthetase 1 is allosterically stimulated by N-acetyl-glutamate. This takes about two days for its effects to be seen it takes time for the enzymes to be synthesised by the cell. However, the urea cycle is fairly active all the time as it has a good capacity at all points in time.  

The nitrogen that is used in the urea cycle can come from a number of other amino acids. The nitrogen is transferred to glutamate, aspartate and glutamine by the transaminases mentioned earlier and is then fed into the urea cycle.

The Glucose/Alanine Cycle

The glucose/alanine cycle is the process of collecting amino-N and carbon from muscle and other extrahepatic tissues and transferring carbon and nitrogen to the liver via the blood. This involves the conversion of alanine to pyruvate in the liver. Pyruvate is then converted to glucose through gluconeogenesis and is transported to muscle where it is converted back to pyruvate through glycolysis. This pyruvate is then converted to alanine which travels in the bloodstream to the liver where the cycle repeats.

That's all for this post, if you have any questions please feel free to ask in the 'comments' section below :)