Lysine Degradation


In humans, the catabolism of L-lysine proceeds via a sequence of seven reactions, the last of which feeds into the pathway for fatty acid catabolism. In the first two reactions, lysine is combined with alpha-ketoglutarate to form saccharopine, which in turn is cleaved and oxidized to yield glutamate and alpha-ketoadipic semialdehyde. The latter molecule is further oxidized to alpha-ketoadipate. Alpha-ketoadipate is oxidatively decarboxylated by the alpha-ketoglutarate dehydrogenase complex yielding glutaryl-CoA. Glutaryl-CoA is converted to crotonyl-CoA, crotonyl-CoA is converted to beta-hydroxybutyryl-CoA, and beta-hydroxybutyryl-CoA is converted to acetoacetyl-CoA. The products of lysine catabolism are thus exclusively ketogenic; i.e., under starvation conditions, they can be used for the synthesis of ketone bodies, beta-hydroxybutyrate and acetoacetate, but not for the net synthesis of glucose. Also depicted in this pathway are various byproducts of lysine, including allysine, hydroxylysine and trimethyllysine (and its derivatives). Allysine is a derivative of lysine, used in the production of elastin and collagen. It is produced by the actions of the enzyme lysyl oxidase on lysine in the extracellular matrix and is essential in the crosslink formation that stabilizes collagen and elastin. 5-Hydroxylysine is a hydroxy derivative of lysine and is known as a component of collagen. It is biosynthesized from lysine via oxidation by the enzyme lysyl hydroxylase. When collagen is degraded, hydoxylysine is produced. Carnitine is another key byproduct of lysine metabolism. In humans, about 25% of carnitine is synthesized in the liver, kidney and brain from lysine and methionine. Most of the carnitine in the body comes from dietary sources such as red meat and dairy products. The sequence for carnitine biosynthesis in liver begins with N6-trimethyl-lysine which is transformed to 3-hydroxy-N6-trimethyl-lysine which leads to leads to 4-trimethylammoniobutyrate and then finally to carnitine.

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References

  1. Lehninger, A.L. (2005) Lehninger principles of biochemistry (4 th ed.). New York: W.H Freeman.
  2. Salway, J.G. (2004) Metabolism at a glance (3 rd ed.). Alden, Mass. : Blackwell Pub.