This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Synonyms: vitamin C biosynthesis, L-ascorbic acid biosynthesis IV
|Superclasses:||Biosynthesis → Cofactors, Prosthetic Groups, Electron Carriers Biosynthesis → Vitamins Biosynthesis → Ascorbate Biosynthesis|
Expected Taxonomic Range:
Vitamin C ( L-ascorbate), a reducing agent and antioxidant, is a cofactor in reactions catalyzed by copper-dependent monooxygenases and iron-dependent dioxygenases. It is synthesized, in vertebrates having this capacity, from D-glucuronate. This compound is formed through direct hydrolysis of UDP-α-D-glucuronate by enzyme(s) bound to the endoplasmic reticulum membrane. They share many properties with, and are most likely identical to, UDP-glucuronosyltransferases [Linster07a].
L-ascorbate can be biosynthesized by plants (see L-ascorbate biosynthesis I (L-galactose pathway)), some bacteria (see L-ascorbate biosynthesis III) and many vertebrates. It is used in the pharmaceutical industry for the production of vitamin supplements, cosmetics and therapeutic preparations. It is also used in the food, beverage and animal feed industries.
L-ascorbate is an essential vitamin in the diet of humans, non-human primates and certain other vertebrates that cannot biosynthesize it (some fish and birds, bats and guinea pigs). These species rely on mechanisms for efficient uptake and recycling of this vitamin (see pathway ascorbate recycling (cytosolic)). It is taken up in the intestine, transported in plasma and delivered to tissues. Its recycling in erythrocytes has been described (reviewed in [May98]). It has roles in collagen biosynthesis, as an antioxidant, as a cofactor in reactions catalyzed by some metal-dependent mono- and dioxygenases, and may be involved in cell signaling reactions and transcription factor activation. A deficiency of vitamin C leads to the disorder scurvy (reviewed in [Bremus06, Linster07a]). Yeasts are known to biosynthesize D-erythroascorbate, a 5-carbon analog of ascorbate. It functions as an antioxidant, but it lacks antiscorbutic activity (prevention of scurvy) (reviewed in [Bremus06]).
The mammalian liver pathway for L-ascorbate biosynthesis is shown here. D-glucuronate is formed from hydrolysis of UDP-α-D-glucuronate by a membrane-bound enzyme(s) of the endoplasmic reticulum, probably UDP-glucuronidase(s) (reviewed in [Linster07a]. The ultimate precursor of UDP-α-D-glucuronate is D-glucose (see pathway UDP-D-xylose biosynthesis). D-glucuronate is reduced to L-gulonate by a NADP+-dependent aldehyde reductase. A broad specificity lactonase then forms L-gulono-1,4-lactone. The L-gulono-1,4-lactone is oxidized to L-ascorbate by L-gulonolactone oxidase via an intermediate lactone which spontaneously isomerizes to L-ascorbate. The production of hydrogen peroxide by this endoplasmic reticulum enzyme is unusual and transfer of electrons to another acceptor might occur in intact cells, as has been shown for plant homologues of this enzyme. L-Gulonolactone oxidase is deficient in humans and other animals unable to biosynthesize L-ascorbate due to mutations in the gene encoding it [Nishikimi94]. Reviewed in [Linster07a, May98]).
Variants: L-ascorbate biosynthesis I (L-galactose pathway), L-ascorbate biosynthesis II (L-gulose pathway), L-ascorbate biosynthesis III, L-ascorbate biosynthesis V, L-ascorbate biosynthesis VI (engineered pathway)
Nishikimi94: 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(18);13685-8. PMID: 8175804
ElKabbani94: El-Kabbani O, Green NC, Lin G, Carson M, Narayana SV, Moore KM, Flynn TG, DeLucas LJ (1994). "Structures of human and porcine aldehyde reductase: an enzyme implicated in diabetic complications." Acta Crystallogr D Biol Crystallogr 50(Pt 6);859-68. PMID: 15299353
Ha04: Ha MN, Graham FL, D'Souza CK, Muller WJ, Igdoura SA, Schellhorn HE (2004). "Functional rescue of vitamin C synthesis deficiency in human cells using adenoviral-based expression of murine l-gulono-gamma-lactone oxidase." Genomics 83(3);482-92. PMID: 14962674
IsherwoodD60: IsherwoodD FA, MapsonLW, Chen YT (1960). "Synthesis of L-ascorbic acid in rat-liver homogenates. Conversion of L-gulono- and L-galactono-gamma-lactone and the respective acids into L-ascorbic acid." Biochem J 76;157-71. PMID: 14405898
Kaufman81: Kaufman EE, Nelson T (1981). "Kinetics of coupled gamma-hydroxybutyrate oxidation and D-glucuronate reduction by an NADP+-dependent oxidoreductase." J Biol Chem 256(13);6890-4. PMID: 7240249
Kondo06: Kondo Y, Inai Y, Sato Y, Handa S, Kubo S, Shimokado K, Goto S, Nishikimi M, Maruyama N, Ishigami A (2006). "Senescence marker protein 30 functions as gluconolactonase in L-ascorbic acid biosynthesis, and its knockout mice are prone to scurvy." Proc Natl Acad Sci U S A 103(15);5723-8. PMID: 16585534
Koshizaka88: Koshizaka T, Nishikimi M, Ozawa T, Yagi K (1988). "Isolation and sequence analysis of a complementary DNA encoding rat liver L-gulono-gamma-lactone oxidase, a key enzyme for L-ascorbic acid biosynthesis." J Biol Chem 263(4);1619-21. PMID: 3338984
©2015 SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025-3493