Degradation of amino acid carbon skeletons
About twenty amino acids are incorporated into human proteins (there are 22 of them including selenocysteine and pyrrolysine ). Amino acids that are not used in metabolism for any reason, e.g. after they have been released from proteins, are not excreted as a whole, but are catabolized into smaller fragments. At the beginning of the degradation, the amino group is usually split off. Then the remaining carbon skeleton is broken down. The pathways through which this happens are variously complex. Here we will show the common mechanisms and give some examples.
The breakdown of the carbon skeleton of all amino acids ends in one of these seven substances:
- pyruvate,
- acetyl-CoA,
- acetoacetyl-CoA,
- α-ketoglutarate,
- succinyl-CoA,
- fumarate,
- oxalacetate.
These products then enter the energy metabolism. They can either be further oxidized to carbon dioxide and water in the Krebs cycle, or they can be converted to other fuels. Some can produce glucose , others only ketone bodies and fatty acids . Accordingly, we distinguish between so-called glucogenic and ketogenic amino acids.
Ketogenic amino acids include those that lead to the formation of acetyl-CoA and acetoacetyl-CoA – leucine and lysine (beginning with the letter L). Glucogenic amino acids include those that lead to the formation of the remaining five products - pyruvate , α-ketoglutarate , succ-CoA , fumarate or oxaloacetate - serine, threonine, cysteine, methionine, aspartate, glutamate, asparagine, glutamine, glycine, alanine, valine, proline, histidine and arginine.
There are also amino acids with two degradation products – one of them is glucogenic and the other is ketogenic. We call them keto and glucogenic amino acids – they include isoleucine, phenylalanine, tyrosine a tryptophan.
The following overview shows which amino acids are degraded into which products:
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1) Acetyl-CoA and acetoacetyl-CoA
- purely ketogenic are Lys and Leu, several other amino acids provide degradation products both glucogenic and ketogenic – Phe, Tyr, Trp, Ile;
2) α-ketoglutarate
- Five-carbon – Glu, Gln, Pro, Arg and His;
3) Suc-CoA
- non-polar amino acids – Met, Ile a Val;
4) Fumarate
- Phe, Tyr;
5) Oxalacetate
- four-carbon amino acids – Asp a Asn;
6) Pyruvate
- Cys, Ala, Ser, Gly, Thr, Trp.
Degradation of branched-chain amino acids – Val, Leu and Ile
It is characteristic of these amino acids that they are degraded not in liver cells, but mainly in extrahepatic tissues – high activity especially in muscle cells. These contain a specific transaminase producing the respective α-keto acids – the so-called keto analogues of branched amino acids . This transaminase is absent in liver cells. Keto analogs are converted to acyl-CoA derivatives by the action of a dehydrogenation complex , which catalyzes oxidative decarboxylation and dehydrogenation.
