| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1987: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1986: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Research Abstract |
Exhaustion of urea cycle intermediates should lead to impaired ammonia metabolism. Such exhaustion will occur if supply of ornithine to liver from small intestine is impaired, possibly by its lowered synthesis from glutamate. Using rat models, I examined various factors which may influence the activities of pyrroline-5-carboxylate(P5C) synthase, the rate limiting enzyme of ornithine and proline biosynthesis from glutamate. First I developed a highly sensitive and specific assay procedure of the activities. This enabled to detect as low as 30 pmol synthesis. After an extensive survey over 30 tissues of the rat, I found that this activity is concentrated in the upper small intestine. The thymus, pancras and lymph node had some activities whereas the liver, kidney and skeletal muscle had none. There was no difference in the specific activities between male and female rats. The activities in the whole small intestines were lower in 3-years old rats compared to the younger controls. The activities were much lower in the STZ-treated diabetic rats. Aspirin, aminopyrine and caprylic acid, which are Reye syndromerelated antipyretics, inhibited the activity by about 20%. I also found the activity in the human small intestine, having the same enzymological requirements for ATP, NADPH and MgCl_2. Finally, I developed a new sensitive procedure for the assay of acetylglutamate synthase activity, and found that the kidney, pancreas, testis, lung and brown fat had substancial activities, which had not been described. The results described above suggest that the Reye-related compounds are not likely to cause impaired ornithine supply to the liver by inhibiting P5C synthase activity in the small intestine. Rather, a possible decrease of the activities in the aged or diabetics may predispose man to increased demand for exogenous intake of proline and arginine.
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