Preparation of four optical isomers of hydroxylated hexobarbital and activities of 3-hydroxyhexobarbital dehydrogenase from guinea pig and rabbit liver.
The preparation of four optical isomers of 3'-hydroxyhexobarbital [5-(3'-hydroxy-1'-cyclohexen-1'-yl)-1,5-dimethylbarbituric acid] is described. The absolute configuration of the four isomers were assigned as (3'S, 5 R) and (3'R, 5R) for alpha- and beta-isomers from (R)-(--)-hexobarbital, respectively. Some of these isomeric 3'-hydroxyhexobarbitals, which are formed in the reaction of hexobarbital with liver microsomal mono-oxygenase, are oxidized to 3'-oxohexobarbital [5-(3'-oxo-1'-cyclohexen-1'-yl)-1,5-dimethylbarbituric acid] by dehydrogenase localized in the soluble fraction of liver homogenates. Comparison of activities among the four isomers for 3-hydroxyhexobarbital dehydrogenase was made by use of enzymes from guinea pig and rabbit liver. It became evident that either enzyme had a quite different activity towards each optical isomer, and the configuration of the 3'-position of hydroxyhexobarbital was an important factor affecting the reactivity of enzyme; isomers with 3'S-configuration were preferentially dehydrogenated to enantiomers with 3'R-configuration. Both enzymes had the highest activity towards (3'S, 5R)-3'-(--)-hydroxy-(--)-hexobarbital, irrespective of their having specificity towards different types of substrates.
D000429:Alcohol Oxidoreductases / Q000378:metabolism*; D000818:Animals; D006168:Guinea Pigs; D006591:Hexobarbital / Q000031:analogs & derivatives / Q000302:isolation & purification* / Q000378:metabolism; D008099:Liver / Q000032:analysis / Q000201:enzymology*; D008297:Male; D008968:Molecular Conformation; D011817:Rabbits; D051381:Rats; D013237:Stereoisomerism
D006591:Hexobarbital; D000429:Alcohol Oxidoreductases; C021397:3-hydroxyhexobarbital dehydrogenase