ASCORBATE METABOLISM AND ITS REGULATION IN ANIMALS

This article provides a comprehensive review on ascorbate metabolism i n animal cells, especially in hepatocytes. The authors deal with the s ynthesis and the breakdown of ascorbate as a part of the antioxidant a nd carbohydrate metabolism. Hepatocellular and interorgan cycles with the participation of ascorbate are proposed, based on experiments with murine and human cells; reactions of hexuronic acid pathway, non-oxid ative branch of the pentose phosphate cycle, glycolysis and gluconeoge nesis are involved, Besides the well-known redox coupling between the two major water-soluble antioxidants (glutathione and ascorbate), thei r metabolic links have been also outlined. Glycogenolysis as a major s ource of UDP-glucuronic acid determines the rate of hexuronic acid pat hway leading to ascorbate synthesis. Glycogenolysis is regulated by ox idized and reduced glutathione; therefore, glycogen, ascorbate and glu tathione metabolism are related to each other. Hydrogen peroxide forma tion, due to the activity of gulonolactone oxidase catalyzing the last step of ascorbate synthesis, also affects the antioxidant status in h epatocytes. Based on new observations a complex metabolic regulation i s supposed. Its element might be present also in humans who lost gulon olactone oxidase but they need and metabolize ascorbate. Finally, the obvious disadvantages and the possible advantages of the lost ascorbat e synthesizing ability in humans are considered. (C) 1997 Elsevier Sci ence Inc.