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.