| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1990: ¥200,000 (Direct Cost: ¥200,000)
Fiscal Year 1989: ¥1,800,000 (Direct Cost: ¥1,800,000)
|
|---|
| Research Abstract |
The role and characteristics of the enzyme in human erythrocyte for reductive reaction of keto-bile acid were studied by using dehydrocholic acid, and the following results were obtained :
(1). Partial purification of this enzyme in human erythrocyte has been tried by the method of Bersus et al. Based on the data from the experiment on this enzyme system of erythrocyte, we demonstrated that reduction of dehydrocholic acid was restricted to keto-group C-3 position.
(2). According to previous papers, it had been accepted that dehydrocholic acid is metabolized by hepatic enzymes after intravenous administration and the metabolites were excreted into bile. Major metabolite (70%) was 3alpha, 7alpha-dihydroxy-12-keto bile acid, the second (20%) 3alpha-hydroxy-7, 12-diketo bile acid and the third (10%) cholic acid. In the present study, we demonstrated a rapid increase of serum unconjugated 3alpha-hydroxy-7, 12diketo cholanoic acid after intravenous administration of dehydrocholic acid : this fact indicates dehydrocholic acid could be partially metabolized by the enzyme in erythrocyte, and an altered pathway for metabolism of dehydrocholic acid could be present. Based on the data from quantitative analysis of biotransformed metabolites, we calcurated roughly that 20% and more of injected dehydrocholic acid could be reduced to 3alpha-hydroxy-7, 12-diketoーcholanoic acid in peripheral blood before hepatic uptake. Then, keto-groups at C-7 and C-12 position of this metabolite could be reduced by hepatic enzyme in microsome fraction, and excreted into bile.
(3). Although 3-ketoーbile acids might be produced in colon by an action of intesinal bacteria, a significant amount of this bile acid has been hardly detected. This finding could be illustrated by the enzyme catalyzing the reduction of keto group at C-3 position in erythrocyte.
|
