Catalytic properties of carbonyl reductase from rabbit liver for analogs of acetohexamide and 4-acetylpyridine.
A correlation was observed between the values of specificity constant (kcat/Km) of carbonyl reductase from rabbit liver for acetohexamide analogs and their partition coefficients. This result indicates that the hydrophobicity in straight-chain alkyl groups of acetohexamide analogs plays an important role in the catalytic activity and substrate-binding capacity of the enzyme. Furthermore, the double logarithmic plots of kcat/Km values of the enzyme for 4-acetylpyridine analogs with a straight-chain alkyl group up to five carbon atoms against their partition coefficients gave a straight line. On the other hand, the plots for 4-acetylpyridine analogs with a straight-chain alkyl group over five carbon atoms and with a branched-chain alkyl group were away from the straight line. It is reasonable to postulate that a hydrophobic pocket is located in the substrate-binding domain of the enzyme.
Imamura
Y
Y
Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Koga
T
T
Higuchi
T
T
Otagiri
M
M
Sugino
E
E
Hibino
S
S
Nagumo
S
S
Akita
H
H
D000092:Acetohexamide / Q000031:analogs & derivatives*; D000429:Alcohol Oxidoreductases / Q000302:isolation & purification / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002384:Catalysis; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D011725:Pyridines; D011817:Rabbits; D013379:Substrate Specificity
D011725:Pyridines; D000429:Alcohol Oxidoreductases; C055538:4-acetylpyridine; D000092:Acetohexamide