12.1 Overview of amino acid degradation

All amino acids contain at least one nitrogen atom, which forms their α-amino group. Some amino acids ¹ contain additional nitrogen atoms in their side chains. Nitrogen has no use in energy metabolism and has to be eliminated. There are two key processes in metabolic nitrogen elimination:

Transamination removes the α-amino group from one amino acid and transfers it to α-ketoglutarate. This leads to the accumulation of glutamate.
The release of nitrogen from glutamate and its conversion to urea. This is accomplished by the urea cycle in the liver.

Removal of nitrogen is typically an early step in amino acid degradation and leaves behind the carbon skeleton. The structure of the latter is different for each amino acid, and accordingly each amino acid has its specific pathway of degradation. However, they can be grouped into two broad classes.

As Figure 12-1 shows, most amino acids can be converted to intermediates of the citric acid cycle or to pyruvate. These are called glucogenic amino acids, since they can contribute to the synthesis of glucose (gluconeogenesis). Those that yield acetoacetate are called ketogenic, since acetoacetate is one of the two 'ketone bodies' (as discussed in the chapter on lipid metabolism).

What happens to glucogenic amino acids when they are available in excess over the demand for glucose? This may well happen if we are on a very protein-rich diet. One option would be to first convert all substrates to oxaloacetate in the citric acid cycle and then short-circuit gluconeogenesis and glycolysis at the level of phosphoenolpyruvate:

Oxaloacetate + GTP → PEP + GDP + CO₂

PEP + ADP → pyruvate + ATP

Although this would seem reasonably straightforward, this pathway is apparently not quantitatively important. Instead, the substrates are drained from the TCA cycle at the level of malate by malic enzyme:

Malate + NADP⁺→ pyruvate + NADPH + H⁺ + CO₂

An advantage of this pathway is that it gives us an NADPH instead of NADH that, in the first case, would arise in the formation of oxaloacetate from by malate dehydrogenase. NADPH can be used for fatty acid synthesis, which is the most likely use of excess pyruvate after converson to acetyl-CoA by pyruvate dehydrogenase.

1: Arginine, histidine, lysine, proline, tryptophan, glutamine, asparagine - quite a few, actually. For these side chain amino groups, special 'adapter' pathways exist that ultimately also feed the nitrogen into the urea cycle.