Vitamin C

Vitamin C (chemical names: ascorbic acid and ascorbate) is a six-carbon lactone which is synthesised from glucose by many animals. Vitamin C is synthesised in the liver in some mammals and in the kidney in birds and reptiles. However, several species – including humans, non-human primates, guinea pigs, Indian fruit bats, and Nepalese redvented bulbuls – are unable to synthesise vitamin C. When there is insufficient vitamin C in the diet, humans suffer from the potentially lethal deficiency disease scurvy. Humans and primates lack the terminal enzyme in the biosynthetic pathway of ascorbic acid, lgulonolactone oxidase, because the gene encoding for the enzyme has undergone substantial mutation so that no protein is produced. 

Role in human metabolic processes

Background biochemistry

Vitamin C is an electron donor (reducing agent or antioxidant), and probably all of its biochemical and molecular functions can be accounted for by this function. 

Enzymatic functions

Vitamin C acts as an electron donor for 11 enzymes. Three of those enzymes are found in fungi but not in humans or other mammals. They are involved in reutilisation pathways for pyrimidines and the deoxyribose moiety of deoxynucleosides. Of the 8 remaining human enzymes, three participate in collagen hydroxylation  and two in carnitine biosynthesis; of the three enzymes which participate in collagen hydroxylation, one is necessary for biosynthesis of the catecholamine norepinephrine, one is necessary for amidation of peptide hormones, and one is involved in tyrosine metabolism.

Ascorbate interacts with enzymes having either monooxygenase or dioxygenase activity. The monooxygenases dopamine β-monooxygenase and peptidyl-glycine α- monooxygenase incorporate a single oxygen atom into a substrate, either a dopamine or a glycine-terminating peptide. The remaining enzymes are dioxygenases which incorporate two oxygen atoms in two different ways. The enzyme 4-hydroxyphenylpyruvate dioxygenase incorporates two oxygen atoms into one product. The other dioxygenase incorporates one oxygen atom into succinate and one into the enzyme-specific substrate.

Miscellaneous functions

The concentrations of vitamin C in gastric juice were several fold higher (median, 249 μmol/l; range, 43–909 μmol/l) than those found in the plasma of the same normal subjects (39 μmol/l, 14–101 μmol/l) (17). Gastric juice vitamin C may prevent the formation of N-nitroso compounds, which are potentially mutagenic. High intakes of vitamin C correlate with reduced gastric cancer risk, but a cause-and-effect relationship has not been established. Vitamin C protects low-density lipoproteins ex vivo against oxidation and may function similarly in the blood.

A common feature of vitamin C deficiency is anaemia. The antioxidant properties of vitamin C may stabilise folate in food and in plasma, and increased excretion of oxidized folate derivatives in human scurvy was reported. Vitamin C promotes absorption of soluble non-haem iron possibly by chelation or simply by maintaining the iron in the reduced (ferrous, Fe2+) form. The effect can be achieved with the amounts of vitamin C obtained in foods. However, the amount of dietary vitamin C required to increase iron absorption ranges from 25 mg upwards and depends largely on the amount of inhibitors, such as phytates and polyphenols, present in the meal. 

References:

Stewart, C.P. & Guthrie, D. [Editors] (1953). Lind’s treatise on scurvy. Edinburgh, University Press.

Nishikimi, M., Fukuyama, R., Minoshima, S., Shimizu, N. & Yagi, K. 1994. Cloning and chromosomal mapping of the Human nonfunctional gene for L-gulono-gamma-lactone oxidase, the enzyme for L-ascorbic acid biosynthesis missing in man. J. Biol. Chem., 269: 13685-13688.

Levine, M. 1986. New concepts in the biology and biochemistry of ascorbic acid. N. Engl. J. Med., 314:892-902.

Englard, S. & Seifter, S. 1986. The biochemical functions of ascorbic acid. Annu. Rev. Nutr., 6: 365-406: 365-406.

Wondrack, L.M., Hsu, C.A. & Abbott, M.T. 1978. Thymine 7-hydroxylase and pyrimidine deoxyribonucleoside 2'-hydroxylase activities in Rhodotorula glutinis. J. Biol. Chem., 253: 6511-6515.

Stubbe, J.A. 1985. Identification of two alpha keto glutarate dependent dioxygenases in extracts of Rhodotorula glutinis catalysing deoxyuridine hydroxylation. J. Biol. Chem., 260: 9972-9975.

Prockop, D.J. & Kivirikko, K.I. 1995. Collagens: molecular biology, diseases, and potential for therapy. Annu. Rev. Biochem., 64: 403-434.

Peterkofsky, B. 1991. Ascorbate requirement for hydroxylation and secretion of procollagen: relationship to inhibition of collagen synthesis in scurvy. Am. J. Clin. Nutr., 54:1135S-1140S.

Kivirikko, K.I. & Myllyla, R. 1985. Post-translational processing of procollagens. Ann. NY Acad. Sci., 460: 187-201.

Rebouche, C.J. 1991. Ascorbic acid and carnitine biosynthesis. Am. J. Clin. Nutr., 54: 1147S-1152S.

Dunn, W.A., Rettura, G., Seifter, E. & Englard, S. 1984. Carnitine biosynthesis from gamma-butyrobetaine and from exogenous protein-bound 6-N-trimethyl-L-lysine by the perfused guinea pig liver. Effect of ascorbate deficiency on the in situ activity of gamma-butyrobetaine hydroxylase. J. Biol. Chem., 259: 10764-10770.

Levine, M., Dhariwal, K.R., Washko, P.W., Butlesr, J.D., Wang, Y.H. & Bergsten, P. 1991. Ascorbic acid and in situ kinetics: a new approach to vitamin requirements. Am. J. Clin. Nutr., 54: 1157S-1162S.

Kaufman, S. 1974. Dopamine-beta-hydroxylase. J. Psychiatr. Res., 11: 303-316.

Eipper, B., Milgram, S.L., Husten, E.J., Yun, H. & Mains, R.E. 1993. Peptidylglycine alpha amidating monooxygenase: a multifunctional protein with catalytic, processing, and routing domains. Prot Sci. 2: 489-497.

Eipper, B., Stoffers, D.A. & Mains, R.E. 1992. The biosynthesis of neuropeptides: peptide alpha amidation. Annu. Rev. Neurosci., 15: 57-85.

Lindblad, B., Lindstedt, G. & Lindstedt, S. 1970. The mechanism of enzymic formation of homogentisate from p-hydroxyphenyl pyruvate. J. Am. Chem. Soc., 92: 7446-7449.

Schorah, C.J., Sobala, G.M., Sanderson, M., Collis, N. & Primrose, J.M. 1991. Gastric juice ascorbic acid: effects of disease and implications for gastric carcinogenesis. Am. J. Clin. Nutr., 53: 287S-93S.

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Byers, T. & Guerrero, N. 1995. Epidemiologic Evidence for vitamin C and vitamin E in
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Hallberg, D., Brune, M. & Rossander-Hulthen, L. 1987. Is there a physiological role of vitamin C in iron absorption. Ann. NY Acad. Sci., 498: 324-332

Hallberg, L., Rossander, L., Persson, H. & Svahn, E. 1982. Deleterious effects of prolonged warming of meals on ascorbic acid content and iron absorption. Am. J. Clin. Nutr., 36: 846-850

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