Carbonyl (phenone) reductase in human liver: inter-individual variability.
The enzyme family carbonyl reductase, which catalyses the reduction of xenobiotic as well as endogenous ketones and aldehydes, has not been very well studied in terms of its biological functions and structural aspects. The aim of the present study was to check for the occurrence of inter-individual variability of carbonyl reductase activity in human liver. In vitro metabolism of p-nitroacetophenone (PNAP, a prototype substrate) indicated the presence of a high- and low-affinity enzyme site. The reductase activity of 17 kidney donor livers was screened at two concentrations (0.05 and 0.5 mM PNAP, below and above Km). The rates of reductase activity at 0.05 mM suggested a normal distribution. In contrast, at 0.5 mM the rates indicated a non-normal distribution, i.e. bi- or tri-modality. As an index of variability of enzyme affinity, ratios of velocities at 0.5 to 0.05 mM PNAP were calculated in order to check their frequency distributions. Three out of 17 kidney donor livers showed an atypical ratio. In these three cases, the high ratio was due to the low activity of the high affinity form of carbonyl reductase. Autopsy livers are a more readily available tissue source and about half the activity of the kidney donor livers was found in 43 autopsy livers indicating that they are a useful source of human tissue for studies of carbonyl reductase.
Department of Pharmacology, Faculty of Medicine, University of Toronto, Canada.
J M
JM
Wong
W
W
Kalow
D
D
Kadar
Y
Y
Takamatsu
T
T
Inaba
D000098:Acetophenones / Q000378:metabolism*; D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D001711:Biotransformation; D014644:Genetic Variation; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000201:enzymology*; D010084:Oxidation-Reduction
D000098:Acetophenones; C001972:4-nitroacetophenone; D000429:Alcohol Oxidoreductases; D005982:Glutathione Transferase