Higher activity of polymorphic NAD(P)H:quinone oxidoreductase in liver cytosols from blacks compared to whites.
In human liver, the two-electron reduction of quinone compounds, such as menadione is catalyzed by cytosolic carbonyl reductase (CBR) and NAD(P)H:quinone oxidoreductase (NQO1) activities. We assessed the relative contributions of CBR and NQO1 activities to the total menadione reducing capacity in liver cytosols from black (n=31) and white donors (n=63). Maximal menadione reductase activities did not differ between black (13.0+/-5.0 nmol/min mg), and white donors (11.4+/-6.6 nmol/min mg; p=0.208). In addition, both groups presented similar levels of CBR activities (CBR(blacks)=10.9+/-4.1 nmol/min mg) versus CBR(whites)=10.5+/-5.8 nmol/min mg; p=0.708). In contrast, blacks showed higher NQO1 activities (two-fold) than whites (NQO1(blacks)=2.1+/-3.0 nmol/min mg versus NQO1(whites)=0.9+/-1.6 nmol/min mg, p<0.01). To further explore this disparity, we tested whether NQO1 activity was associated with the common NQO1(*)2 genetic polymorphism by using paired DNA samples for genotyping. Cytosolic NQO1 activities differed significantly by NQO1 genotype status in whites (NQO1(whites[NQO1*1/*1])=1.3+/-1.7 nmol/min mg versus NQO1(whites[NQO1*1/*2+NQO1*2/*2])=0.5+/-0.7 nmol/min mg, p<0.01), but not in blacks (NQO1(blacks[NQO1*1/*1])=2.6+/-3.4 nmol/min mg versus NQO1(blacks[NQO1*1/*2])=1.1+/-1.2 nmol/min mg, p=0.134). Our findings pinpoint the presence of significant interethnic differences in polymorphic hepatic NQO1 activity.
Covarrubias
Vanessa Gonzalez
VG
Department of Pharmaceutical Sciences, The State University of New York at Buffalo, 545 Cooke Hall, Buffalo, NY 14260-1200, USA.
Lakhman
Sukhwinder S
SS
Forrest
Alan
A
Relling
Mary V
MV
Blanco
Javier G
JG
D000328:Adult; D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000378:metabolism; D000449:Aldehyde Reductase; D000074408:Aldo-Keto Reductases; D044383:Black People / Q000235:genetics*; D003600:Cytosol / Q000201:enzymology*; D005260:Female; D005838:Genotype; D006801:Humans; D008099:Liver / Q000166:cytology / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism*; D011110:Polymorphism, Genetic; D024483:Vitamin K 3 / Q000493:pharmacokinetics; D044465:White People / Q000235:genetics*
D024483:Vitamin K 3; D000429:Alcohol Oxidoreductases; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human