Ascorbate metabolism and its regulation in animals.

This article provides a comprehensive review on ascorbate metabolism in animal cells, especially in hepatocytes. The authors deal with the synthesis and the breakdown of ascorbate as a part of the antioxidant and 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-oxidative branch of the pentose phosphate cycle, glycolysis and gluconeogenesis are involved. Besides the well-known redox coupling between the two major water-soluble antioxidants (glutathione and ascorbate), their metabolic links have been also outlined. Glycogenolysis as a major source of UDP-glucuronic acid determines the rate of hexuronic acid pathway leading to ascorbate synthesis. Glycogenolysis is regulated by oxidized and reduced glutathione; therefore, glycogen, ascorbate and glutathione metabolism are related to each other. Hydrogen peroxide formation, due to the activity of gulonolactone oxidase catalyzing the last step of ascorbate synthesis, also affects the antioxidant status in hepatocytes. Based on new observations a complex metabolic regulation is supposed. Its element might be present also in humans who lost gulonolactone oxidase but they need and metabolize ascorbate. Finally, the obvious disadvantages and the possible advantages of the lost ascorbate synthesizing ability in humans are considered.