Studies on analogues of succinic semialdehyde as substrates for succinate semialdehyde dehydrogenase from rat brain.
The methyl ester of succinic semialdehyde (SSA) was examined as a substrate for succinate semialdehyde dehydrogenase (SSADH) from rat brain. It was found that the ester can be oxidized by the enzyme. Values of Km for SSA-Me were higher than for those for SSA, and for this substrate the enzyme showed a substrate-dependent inhibition. This finding suggests that the carboxylate group of SSA is not essential in the process of inhibition of SSADH by the substrate. Cyclopropyl analogues of SSA, cis- and trans-1-formyl-cyclopropan-2-carboxylic acids, were also individually tested as substrates of SSADH. Only the trans isomer was found to be oxidized to the corresponding dicarboxylic acid; it inhibited the enzyme in the same range of concentrations as SSA. The above data suggest that, as for gamma-aminobutyric acid, SSA is present in an unfolded, transoid conformation at the active site of SSADH.
Manzocchi
A
A
Biondi
P
P
Secchi
C
C
Santaniello
E
E
D000445:Aldehyde Oxidoreductases / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000201:enzymology*; D003521:Cyclopropanes / Q000378:metabolism; D007536:Isomerism; D007700:Kinetics; D051381:Rats; D050644:Succinate-Semialdehyde Dehydrogenase; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000378:metabolism
D003521:Cyclopropanes; C048914:1-formylcyclopropane-2-carboxylic acid; D005680:gamma-Aminobutyric Acid; D000445:Aldehyde Oxidoreductases; C493647:Aldh5a1 protein, rat; D050644:Succinate-Semialdehyde Dehydrogenase; C009338:succinic semialdehyde