PathwayStep2460 PathwayStep2458 PathwayStep2459 PathwayStep2456 PathwayStep2457 PathwayStep2454 PathwayStep2455 PathwayStep2453 Lysine catabolism Authored: D'Eustachio, P, 2003-06-24 00:00:00 Edited: D'Eustachio, P, 0000-00-00 00:00:00 GENE ONTOLOGYGO:0006554 ISBN0079130356 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). Pubmed12126930 Pubmed6434529 Reactome Database ID Release 4371064 Reactome, http://www.reactome.org ReactomeREACT_1298 lysine + alpha-ketoglutarate +NADPH + H+ => saccharopine + NADP+ + H2O Exchange of cytosolic 2-oxoadipate for mitochondrial 2-oxoglutarate alpha-ketoadipate + glutamate <=> alpha-aminoadipate + alpha-ketoglutarate glutaryl-CoA + FAD => crotonyl-CoA + FADH2 + CO2 alpha-ketoadipate + CoASH + NAD+ => glutaryl-CoA + CO2 + NADH + H+ saccharopine + NAD+ + H2O => alpha-aminoadipic semialdehyde + glutamate + NADH + H+ alpha-aminoadipate + alpha-ketoglutarate <=> alpha-ketoadipate + glutamate alpha-aminoadipic semialdehyde + NAD+ => alpha-aminoadipate + NADH + H+