Reactome | Lysine catabolism

Lysine catabolism

Stable Identifier

R-HSA-71064

DOI

10.3180/REACT_1298.1

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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In humans, most catabolism of L-lysine normally proceeds via a sequence of seven reactions which feeds into the pathway for fatty acid catabolism. In the first two reactions, catalyzed by a single enzyme complex, 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 (the same enzyme complex responsible for the conversion of alpha-ketoglutarate to succinyl-CoA in the citric acid cycle), 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 (Cox 2001; Goodman and Freeman 2001).

Literature References

PubMed ID	Title	Journal	Year
	The Metabolic and Molecular Bases of Inherited Disease, 8th ed Scriver, CR, Beaudet, AL, Valle, D, Sly, WS		2001
12126930	Characterization of the human gene encoding alpha-aminoadipate aminotransferase (AADAT). Goh, DL, Patel, A, Thomas, GH, Salomons, GS, Schor, DS, Jakobs, C, Geraghty, MT	Mol Genet Metab	2002
	The Metabolic and Molecular Bases of Inherited Disease, 8th ed Scriver, CR, Beaudet, AL, Valle, D, Sly, WS		2001
6434529	Familial hyperlysinemias. Purification and characterization of the bifunctional aminoadipic semialdehyde synthase with lysine-ketoglutarate reductase and saccharopine dehydrogenase activities. Markovitz, PJ, Chuang, DT, Cox, RP	J Biol Chem	1984