Reduction of drug ketones by dihydrodiol dehydrogenases, carbonyl reductase and aldehyde reductase of human liver

Genetic polymorphisms in the carbonyl reductase 3 gene CBR3 and the NAD(P)H:quinone oxidoreductase 1 gene NQO1 in patients who developed anthracycline‐related congestive heart failure after childhood cancer

“…9,15,16 There are 2 monomeric CBRs (CBR1 and CBR3) encoded for genes located in chromosome 21 (CBR1 21q22.13 and CBR3 21q22.2), and the resulting proteins have 72% of identity at the amino-acid level. The key role of CBR activity during the pathogenesis of anthracycline-related cardiotoxicity has been pinpointed in biochemical and murine studies.…”

The Aldo-Keto Reductase Superfamily and its Role in Drug Metabolism and Detoxification

“…Like its parent, hydroxyhexamide is also pharmacologically active (Imamura et al, 2001). In human liver, AKR1A1 (aldehyde reductase) has been identified to be the major acetohexamide reductase with K m of 0.22 mM and k cat /K m of 17 min −1 mM −1 (Ohara et al, 1995) (Table 4). Three hydroxysteroid dehydrogenases, AKR1C1, C2, and C4 (referred to as dihydrodiol dehydrogenases 1, 2, and 4 in the original report), but not carbonyl reductase, possess such activity, but they have a higher K m and lower catalytic efficiency than AKR1A1 (Ohara et al, 1995).…”

“…In human liver, AKR1A1 (aldehyde reductase) has been identified to be the major acetohexamide reductase with K m of 0.22 mM and k cat /K m of 17 min −1 mM −1 (Ohara et al, 1995) (Table 4). Three hydroxysteroid dehydrogenases, AKR1C1, C2, and C4 (referred to as dihydrodiol dehydrogenases 1, 2, and 4 in the original report), but not carbonyl reductase, possess such activity, but they have a higher K m and lower catalytic efficiency than AKR1A1 (Ohara et al, 1995). In rats, but not humans, androgen-dependent microsomal carbonyl reductase has also been suggested to be involved in acetohexamide metabolism and this enzyme has been linked to interspecies differences in the pharmacokinetics of acetohexamide (Imamura and Shimada, 2005).…”

Activities of biotransformation enzymes and flubendazole metabolism in lambs (Ovis aries): effect of gender and flubendazole therapy

“…The levels of 7-ethoxyresorufin (EROD), 7-methoxyresorufin (MROD), 7-pentoxyresorufin (PROD) O-dealkylases, and 7-benzyloxyresorufin O-dearylase (BROD) activity were determined at 37°C using fluorimetric determination of resorufin [9,51] 7-Penthoxyresorufin O-dealkylase PROD CYP2B [9,50] 7-Benzyloxyresorufin O-dearylase BROD CYP2B, CYP3A [9,50] 7-Methoxy-4-trifluoromethyl-coumarin demethylase MFCD CYP2C [13,40] 6-Chlorzoxazone hydroxylase CXOH CYP2E1, (CYP1A) [39,44] Thiobenzamide oxidase TBSO FMO [10] D,L-glyceraldehyde reductase GALR AKR1A [23] Metyrapone reductase METR (mic, cyt) 11b-HSD 1, AKR1C4, CBR [30] 4-Pyridine-carboxaldehyde reductase PCAR (mic, cyt) 3a-HSD, AKR1A, AKR1C [37] Daunorubicin reductase (pH 8.5) DAUR8 AKR1A [36] Daunorubicin reductase (pH 6.0) DAUR6 AKR1C2, CBR [16,36] Acenaphthenol dehydrogenase ANDH AKR1C1-4 [8,38] Oracin dehydrogenase ORDH (mic, cyt) 11b-HSD 1, AKR1C1-4, CBR [48,52] p-Nitrophenol-UGT UGT UGT [32] 1-Chloro-2,4-dinitrobenzene-GST GST GST [19] foxide, DMSO). Assays were performed using the Perkin-Elmer luminescence spectrophotometer LS 50B, with excitation and emission wavelengths of 530 nm and 585 nm, respectively.…”

“…Spectrophotometric determination (340 nm, 25°C) of NADPH consumption served as the assessment of reductase activities [16,23,30,36,37].…”