Tracer studies of glucuronic acid biosynthesis.

Glucuronic acid has been found in the urine of a variety of experimental animals (1, 2), chiefly in the form of conjugation products with phenolic substances and steroids (2, 3). The presence of glucuronides is widely interpreted as evidence of the ability of the animal organism to make use of the conjugation reaction to eliminate a great variety of toxic substances. Variations in the aglucone structures described in the literature make it evident that the enzymic control of conjugation is not highly specific. The precursors of glucuronic acid or the mechanism of synthesis have not been established (2-l 1). The enzyme /3-glucuronidase (12) apparently is not concerned with the synthesis of the glucuronic acid molecule, but acts merely as a conjugating enzyme (11). Although the structural similarity of glucose and glucuronic acid strongly suggests this carbohydrate as a precursor of glucuronic acid, many investigators (5-10) have concluded that glucose is not directly convertible to glucuronic acid. Glycogen (5, 6), lactic acid (7), the glycogenic amino acids (7), mucin (8), and certain 3-carbon intermediates of carbohydrate metabolism (9, 10) have been suggested as precursors. In this investigation radioactive tracer techniques have shown that in borneol-treated guinea pigs the carbon atoms of glucose are converted to glucuronic acid without a change in the relative activity of carbon in position 6 compared with the total activity in positions 1 to 5. The slight conversion of radioactive sodium bicarbonate to glucuronic acid could be accounted for by an intermediate formation of glucose and glycogen. It was further shown that ascorbic acid is not converted to glucuronic acid in borneol-treated guinea pigs.