Target enzymes on hepatic dysfunction caused by dietary products of lipid peroxidation.
Dietary products of lipid peroxidation cause hepatic dysfunction due to decreases in the activities of some hepatic enzymes and to depletion of CoA. An idea about the decreases and depletion is that the enzymes and CoA could be injured directly by the incorporated products in the liver. Their inactivations in vitro were then examined using a reasonable amount of peroxidation products. The hepatic cytosol, microsomes, and mitochondria were incubated with 10, 15, and 20 micrograms/mg protein of peroxidation products, respectively, and changes in the enzymatic activities were monitored. Glucose-6-phosphate dehydrogenase, mitochondrial NAD-dependent aldehyde dehydrogenase, glucokinase, and glyceradehyde phosphate dehydrogenase were inactivated, and the CoA level was decreased, but the other hepatic enzymes were not. Although glyceraldehyde phosphate dehydrogenase was most sensitive to peroxidation products in vitro, the decrease in activity was not detected by the oral dose of secondary products. On the other hand, among the components of peroxidation products, hydroperoxides and polymers are not incorporated in the liver, but decomposed products of low molecular weight are incorporated. Glucokinase among the above enzymes was not inactivated by the low-molecular-weight products. It was therefore concluded that glucose-6-phosphate dehydrogenase, mitochondrial NAD-dependent aldehyde dehydrogenase, and CoA were targets of the direct attack by incorporated components of peroxidation products in the liver.
Kanazawa
K
K
Department of Agricultural Chemistry, Kobe University, Japan.
Ashida
H
H
D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000818:Animals; D003065:Coenzyme A / Q000378:metabolism; D004041:Dietary Fats / Q000009:adverse effects* / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism / Q000633:toxicity; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D066298:In Vitro Techniques; D008054:Lipid Peroxides / Q000378:metabolism / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013347:Subcellular Fractions / Q000378:metabolism
D004041:Dietary Fats; D005227:Fatty Acids; D008054:Lipid Peroxides; D005954:Glucosephosphate Dehydrogenase; D000444:Aldehyde Dehydrogenase; D003065:Coenzyme A