Stereoselective reduction of 4-benzoylpyridine in the heart of vertebrates.
The stereoselectivity in the reduction of 4-benzoylpyridine (4-BP) was examined in the cytosolic fractions from the heart of 9 vertebrates (pig, rabbit, guinea pig, rat, mouse, chicken, soft-shelled turtle, frog and flounder). 4-BP was stereoselectively reduced to S(-)-alpha-phenyl-4-pyridylmethanol [S(-)-PPOL] in the cytosolic fractions from the heart of pig, rabbit and guinea pig. However, of mammalian heart cytsol tested, only rat heart cytosol had little ability to reduce stereoselectively 4-BP. In an attempt to elucidate this reason, amino acid sequence of rat heart carbonyl reductase (RatHCR) was deduced from the cloned cDNA and compared with that of pig heart carbonyl reductase (PigHCR), which shows a high stereoselectivity in the reduction of 4-BP to S(-)-PPOL. RatHCR showed a high identity with PigHCR in amino acid sequence. Furthermore, recombinant RatHCR was confirmed to reduce stereoselectively 4-BP to S(-)-PPOL with a high optical purity comparable to recombinant PigHCR. It is possible that in the cytosolic fraction from the heart of rat, constitutive reductase other than RatHCR counteracts the stereoselective reduction of 4-BP to S(-)-PPOL, by catalyzing the reduction of 4-BP to the R(+)-enantiomer.
Shimada
Hideaki
H
Kumamoto University, 2-40-1, Kurokami, Kumamoto 860-8555, Japan. hshimada@gpo.kumamoto-u.ac.jp
Imaishi
Koji
K
Hirashima
Takaomi
T
Kitano
Takeshi
T
Ishikura
Shuhei
S
Hara
Akira
A
Imamura
Yorishige
Y
D000429:Alcohol Oxidoreductases / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001711:Biotransformation; D002384:Catalysis; D003600:Cytosol / Q000378:metabolism; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D010084:Oxidation-Reduction; D011725:Pyridines / Q000493:pharmacokinetics*; D016415:Sequence Alignment; D013045:Species Specificity; D013237:Stereoisomerism; D014714:Vertebrates / Q000378:metabolism*
D011725:Pyridines; C066738:4-benzoylpyridine; D000429:Alcohol Oxidoreductases