Differences in the kinetic properties and sensitivity to inhibitors of human placental, erythrocyte, and major hepatic aldehyde dehydrogenase isoenzymes.
(i) The characteristics of the major human hepatic isoenzymes of aldehyde dehydrogenase (ALDH), ALDH I and ALDH II, were compared with the ALDH activities found in human placenta and erythrocytes, (ii) In human liver biopsies, the Km of ALDH I was approximately 7 mumol/L whereas it was 32 mumol/L for ALDH II. The Vmax for ALDH I was 2-3 times greater than the ALDH II Vmax. Human liver ALDH I and II also differed in their sensitivity in inhibitors. Namely, ALDH I was less sensitive to disulfiram than the ALDH II isoenzyme. (iii) ALDH activity in human placenta and erythrocytes was much lower than in liver tissue. Kinetic data showed that placental ALDH isoenzyme had a high Km (in the millimolar range) and increased its activity raising the pH from 7.4 to 8.8, more than the hepatic ALDH I and ALDH II isoenzymes did. Erythrocyte ALDH activity presented a dual component; the smaller one was characterized by a low Km (micromolar range), whereas most of the ALDH activity showed a high Km (millimolar range). (iv) Placental ALDH was resistant to nitrefazole inhibition and was inhibited by disulfiram in a manner similar to the hepatic ALDH I isoenzyme; erythrocyte ALDH was more sensitive to the inhibitory action of disulfiram and nitrefazole. (v) It is concluded that erythrocyte and placental ALDH isoenzymes are different from the hepatic ALDH I and ALDH II forms. It is also suggested that placental and erythrocyte ALDH isoenzymes are different high-Km isoenzymes.
Zorzano
A
A
Departamento de Bioquímica y Fisiología, Facultad de Biología, Universidad de Barcelona, Spain.
Herrera
E
E
D000079:Acetaldehyde / Q000378:metabolism; D000427:Alcohol Deterrents / Q000494:pharmacology; D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004221:Disulfiram / Q000494:pharmacology; D004912:Erythrocytes / Q000201:enzymology*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008297:Male; D009593:Nitroimidazoles / Q000494:pharmacology; D010920:Placenta / Q000201:enzymology*
D000427:Alcohol Deterrents; D007527:Isoenzymes; D009593:Nitroimidazoles; D000444:Aldehyde Dehydrogenase; D000079:Acetaldehyde; D004221:Disulfiram; C013756:nitrefazole