Interindividual variability of carbonyl reductase levels in human livers

Abstract

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 nmol mg protein/min) toward 13, 14-dihydro-15-keto-prostaglandin F 2α (ISKD-PGF 2α), 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-PGF 2α ( 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.