Dihydropyrimidinase. Stereochemistry of the metabolism of some 5-alkylhydantoins.
The (R)- and (S)-isomers of 5-methylhydantoin (5-MH) and of 5-isopropylhydantoin (5-IPH) were synthesized, and incubations of the individual isomers with a rat liver dihydropyrimidinase preparation (100,000g supernatant fraction) were carried out. Only the (R)-isomer of 5-MH or 5-IPH was ring-opened by the enzyme. Reversibility of the enzymatic ring-opening reaction could be demonstrated with only the (R)-isomer of 2-methylhydantoic acid (2-MHA) or 2-isopropylhydantoic acid (2-IPHA). The results of the present investigation show that the replacement in 5-phenylhydantoin of the phenyl group with an alkyl group does not alter the stereospecificity of the hydantoin substrates in the ring-opening reaction. The results are used to form the concept that (R)-dihydrothymine, the optical isomer previously postulated as the natural substrate to the enzyme, may have a different type of binding at the active site of the enzyme.
D000581:Amidohydrolases / Q000378:metabolism*; D000818:Animals; D006827:Hydantoins / Q000138:chemical synthesis / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology; D008297:Male; D008968:Molecular Conformation; D051381:Rats; D013237:Stereoisomerism
D006827:Hydantoins; D000581:Amidohydrolases; C020047:dihydropyrimidinase