Interindividual variability of carbonyl reductase levels in human livers.

Interindividual variability of carbonyl reductase levels in human livers (N = 11) was examined by measuring reductase activity toward various substrates and by western blot analysis using anti-rat ovarian carbonyl reductase CR2 antibody. The carbonyl reductase activity toward p-nitrobenzaldehyde (PNBA) (58.1 +/- 5.4 nmol/mg protein/min, mean +/- SE) was highest among the substrates examined, followed by 4-benzoylpyridine (4BP) (14.4 +/- 2.0 nmol/mg protein/min) and p-nitroacetophenone (PNAP) (2.00 +/- 0.37 nmol/mg protein/min). The reductase activity (6.33 +/- 0.56 pmol/mg protein/min) toward 13,14-dihydro-15-keto-prostaglandin F2 alpha (15KD-PGF2 alpha), which is a diagnostic substrate for rat ovarian carbonyl reductases, was relatively high compared to that in other species. Western blot analysis revealed that each human liver contained several immunoreactive proteins to anti-CR2 antibody. The activities toward 15KD-PGF2 alpha (r = 0.85, P < 0.01) and 4BP (r = 0.84, P < 0.01), but not PNBA (r = 0.53, not significant) or PNAP (r = 0.52, not significant), were closely correlated with the relative amounts of the high molecular weight immunoreactive proteins determined with a densitometer. Thus, the major carbonyl reductases in human liver are similar to those of rat ovarian enzymes.