Saccharopine Dehydrogenase

A number of α‐amino and α‐keto acids have been shown to inhibit saccharopine dehydrogenase [ɛ‐N‐(L‐glutaryl‐2)‐L‐lysine:NAD oxidoreductase (lysine forming)] in the direction of saccharopine formation. Among amino acids those having aliphatic side chains of 5 and 6 carbon atoms were best inhibitors. Dicarboxylic amino acids, aspartate, glutamate, and 2‐aminoadipate were not inhibitory. Kinetic analyses have shown that the inhibition by these compounds was competitive with respect to lysine and uncompetitive with respect to NADH and 2‐oxoglutarate, and are consistent with the mechanism that the amino acid inhibitors combine with the lysinebinding site of the enzyme. α‐Keto acids, on the other hand, produced non‐competitive inhibition with any of the three reactants as the variable. Substrate inhibition by 2‐oxoglutarate and the non‐linear nature of inhibition suggest that these compounds also bind to the enzyme at site(s) other than the active site.