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Target enzymes on hepatic dysfunction caused by dietary products of lipid peroxidation
1Department of Agricultural Chemistry, Kobe University, Japan.
Abstract:
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.
Insights
Dietary lipid peroxidation products harm liver function by directly damaging key enzymes like glucose-6-phosphate dehydrogenase and mitochondrial NAD-dependent aldehyde dehydrogenase, and depleting coenzyme A (CoA). These incorporated products are the primary cause of hepatic dysfunction.
Area of Science:
- Biochemistry
- Hepatology
- Toxicology
Background:
- Dietary lipid peroxidation products are implicated in hepatic dysfunction.
- The mechanism involves potential direct injury to hepatic enzymes and coenzyme A (CoA).
Purpose of the Study:
- To investigate the direct inactivating effects of lipid peroxidation products on hepatic enzymes and CoA in vitro.
- To identify which specific enzymes and molecules are targeted by incorporated peroxidation products in the liver.
Main Methods:
- Incubation of hepatic subcellular fractions (cytosol, microsomes, mitochondria) with varying concentrations of peroxidation products.
- Monitoring changes in enzymatic activities and CoA levels.
- Analysis of the incorporation and effects of different molecular weight components of peroxidation products.
Main Results:
- In vitro inactivation of glucose-6-phosphate dehydrogenase, mitochondrial NAD-dependent aldehyde dehydrogenase, and glyceraldehyde phosphate dehydrogenase was observed.
- A decrease in coenzyme A (CoA) levels was detected.
- Hydroperoxides and polymers were not incorporated, but low-molecular-weight decomposed products were.
- Glucokinase was not inactivated by low-molecular-weight products, and glyceraldehyde phosphate dehydrogenase inactivation was not observed with oral doses.
Conclusions:
- Glucose-6-phosphate dehydrogenase, mitochondrial NAD-dependent aldehyde dehydrogenase, and CoA are direct targets of incorporated lipid peroxidation products in the liver.
- The direct attack by these incorporated components explains the observed hepatic dysfunction.
- Specific low-molecular-weight decomposed products are responsible for the observed enzyme inactivation and CoA depletion.