Catalytic properties for naphthoquinones and partial primary structure of rabbit heart acetohexamide reductase.
The catalytic properties of rabbit heart acetohexamide reductase (RHAR) for naphthoquinones were examined. RHAR efficiently reduced 1,4-naphthoquinone and juglone (5-hydroxy-1,4-naphthoquinone), whereas it had little or no ability to reduce menadione (2-methyl-1,4-naphthoquinone) or plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone). The structural requirements for these four naphthoquinones and one acetohexamide analog, and the kinetic mechanism for the inhibition of acetohexamide reduction by juglone led us to conclude that the 2-methyl group of menadione and plumbagin prevents access of the substrates to the catalytic site of RHAR. Five of six peptides derived from RHAR showed 30-42% residue identities with regions in the amino acid sequence of mouse lung carbonyl reductase (MLCR) belonging to the short-chain dehydrogenase/reductase (SDR) family. The catalytically important residues (Arg-39, Ser-136, Tyr-149 and Lys-153) of MLCR were found in the peptide sequences of RHAR, despite the low residue identities between the two enzymes. RHAR is probably best classified as a member of the SDR family similar to MLCR.
Imamura
Y
Y
Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Koga
T
T
Uriu
Y
Y
Otagiri
M
M
Satoh
K
K
Hara
A
A
D000092:Acetohexamide / Q000378:metabolism; D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002384:Catalysis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D009206:Myocardium / Q000201:enzymology*; D009249:NADP / Q000378:metabolism; D009285:Naphthoquinones / Q000378:metabolism* / Q000494:pharmacology; D010084:Oxidation-Reduction; D011817:Rabbits; D013056:Spectrophotometry, Ultraviolet; D013379:Substrate Specificity
D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D009285:Naphthoquinones; D009249:NADP; D000429:Alcohol Oxidoreductases; C064152:acetohexamide reductase; D000092:Acetohexamide; C005134:juglone