|Gene:||Gulo||Accession Number: G-10075 (MetaCyc)|
Species: Rattus norvegicus
L-Gulono-γ-lactone oxidase catalyzes the last enzymatic step in the vertebrate L-ascorbate (vitamin C) biosynthetic pathway. The high relative molecular mass (500 kDa) of the native enzyme as determined by gel filtration chromatography suggests that it occurs as a large aggregate. The subunit relative molecular mass was determined by SDS-PAGE [Nishikimi79].
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). A deficiency of vitamin C leads to the disorder scurvy (reviewed in [Linster07]). L-Gulonolactone oxidase deficiency in humans and other animals unable to biosynthesize ascorbate is due to mutations in the gene encoding it [Nishikimi94].
In addition to the rat enzyme, the enzyme from Mus musculus (mouse) has been cloned and expressed. Heterologous expression of the mouse enzyme was found to correct the ascorbate biosynthesis deficiency in human cells [Ha04].
Gene Citations: [Koshizaka88]
Locations: endoplasmic reticulum membrane
|Map Position: [45,410,685 <- 45,434,014]|
Molecular Weight of Polypeptide: 50.615 kD (from nucleotide sequence), 51 kD (experimental) [Nishikimi79 ]
Relationship Links: InterPro:IN-FAMILY:IPR006093 , InterPro:IN-FAMILY:IPR006094 , InterPro:IN-FAMILY:IPR007173 , InterPro:IN-FAMILY:IPR010031 , InterPro:IN-FAMILY:IPR010032 , InterPro:IN-FAMILY:IPR016166 , InterPro:IN-FAMILY:IPR016167 , InterPro:IN-FAMILY:IPR016169 , InterPro:IN-FAMILY:IPR023595 , Pfam:IN-FAMILY:PF01565 , Pfam:IN-FAMILY:PF04030 , Prosite:IN-FAMILY:PS00862 , Prosite:IN-FAMILY:PS51387
|Cellular Component:||GO:0005789 - endoplasmic reticulum membrane [Yagi97]|
Enzymatic reaction of: L-gulono-γ-lactone oxidase
The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.
The reaction is physiologically favored in the direction shown.
In Pathways: L-ascorbate biosynthesis IV
L-Gulono-1,4-lactone is oxidized to L-ascorbate by L-gulonolactone-γ-oxidase via an intermediate lactone, L-xylo-hexulonolactone, which spontaneously isomerizes to L-ascorbate (see pathway L-ascorbate biosynthesis IV). 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 (reviewed in [Linster07, May98]).
In the absence of molecular oxygen, phenazine methosulfate acts as an electron acceptor and can be used to assay the dehydrogenase activity of this enzyme. Strong chelating agents had no inhibitory effect on the enzyme [Nishikimi79].
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
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
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
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