Synthesis of 3-arsonoalanine and its action on aspartate aminotransferase and aspartate ammonia-lyase. Comparison with arsenical analogues of malate and fumarate.
DL-3-Arsonoalanine has been synthesized by the Strecker synthesis from the unstable compound arsonoacetaldehyde. It inactivates pig heart cytosolic aspartate aminotransferase and inhibits aspartate ammonia-lyase by competing with aspartate (Ki/Km 0.23). The fumarate analogue (E)-3-arsonoacrylic acid and the malate analogue (RS)-3-arsonolactate also inhibit fumarate hydratase, competing with fumarate (Ki/Km 1.8) and malate (Ki/Km 1.6) respectively. Attempted non-enzymic transamination of 3-arsonoalanine gave elimination of arsenite, in contrast with the transamination of 3-phosphonoalanine, which is either successful or leads to loss of phosphate.
Ali
B R
BR
Department of Biochemistry, University of Cambridge, England.
Dixon
H B
HB
D000409:Alanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D001151:Arsenic / Q000494:pharmacology*; D001152:Arsenicals / Q000138:chemical synthesis* / Q000494:pharmacology; D001219:Aspartate Aminotransferases / Q000037:antagonists & inhibitors*; D001220:Aspartate Ammonia-Lyase / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D005649:Fumarate Hydratase / Q000037:antagonists & inhibitors; D005650:Fumarates / Q000494:pharmacology*; D008293:Malates / Q000494:pharmacology*
D001152:Arsenicals; D004791:Enzyme Inhibitors; D005650:Fumarates; D008293:Malates; C082448:3-arsonoalanine; C030298:malic acid; C032005:fumaric acid; D001219:Aspartate Aminotransferases; D005649:Fumarate Hydratase; D001220:Aspartate Ammonia-Lyase; D001151:Arsenic; D000409:Alanine