The purine pathway in liver is being investigated with relation to the effects of alcohol. The administration of alcohol is known to result in elevated uric acid levels, uric acid turnover, and hyperuricemia. Subsequent to alcohol ingestion or administration, there is an increase in acetate, changes in the blood phosphate levels, and phosphate and pyrophosphate concentrations in liver tissue. We are investigating, in a systematic fashion, the effects of ethanol plus or minus an inhibitor of ethanol metabolism (4-methylpyrazole), and the products of ethanol metabolism acetate and phosphate. The substances are administered to rats, and the livers quick frozen after 30 min. Investigations have been initiated of the effects of these compounds on the metabolites which are involved in purine biosynthesis; the nucleobases and nucleotides; and the key enzymes in the synthetic pathway. Preliminary results indicate that alcohol administration results in the elevation of pentose pathway metabolites, and phosphoribosyl pyrophosphate, which is the rate-limiting substrate in the first step in purine biosynthesis. New methods have been developed for the measurement of metabolites, nucleobases and enzyme activities.
