L-gulonolactone oxidase

L-Gulonolactone oxidase (

Gulonolactone oxidase deficiency

The non-functional gulonolactone oxidase pseudogene (GULOP) was mapped to human

The loss of activity of the gene encoding L-gulonolactone oxidase (GULO) has occurred separately in the history of several species. GULO activity has been lost in some species of bats, but others retain it.

The remnant of this non-functional gene with many mutations is still present in the genomes of guinea pigs and humans.^[8] It is unknown if remains of the gene exist in the bats who lack GULO activity. The function of GULO appears to have been lost several times, and possibly re-acquired, in several lines of passerine birds, where ability to make vitamin C varies from species to species.^[9]

Loss of GULO activity in the primate order occurred about 63 million years ago, at about the time it split into the suborders Haplorhini (which lost the enzyme activity) and Strepsirrhini (which retained it). The haplorhine ("simple-nosed") primates, which cannot make vitamin C enzymatically, include the tarsiers and the simians (apes, monkeys and humans). The strepsirrhine ("bent-nosed" or "wet-nosed") primates, which can still make vitamin C enzymatically, include lorises, galagos, pottos, and, to some extent, lemurs.^[10]

L-Gulonolactone oxidase deficiency has been called "

Johnson et al. have hypothesized that the mutation of the GULOP pseudogene so that it stopped producing GULO may have been of benefit to early primates by increasing uric acid levels and enhancing fructose effects on weight gain and fat accumulation. With a shortage of food supplies this gave mutants a survival advantage.^[18]

Animal models

Studies of human diseases have benefited from the availability of small laboratory animal models. However, the tissues of animal models with a GULO gene generally have high levels of ascorbic acid and so are often only slightly influenced by exogenous vitamin C. This is a major handicap for studies involving the endogenous redox systems of primates and other animals that lack this gene.

Guinea pigs are a popular human model. They lost the ability to make GULO 20 million years ago.^[8]

In 1999, Maeda et al. genetically engineered mice with inactivated GULO gene. The mutant mice, like humans, entirely depend on dietary vitamin C, and they show changes indicating that the integrity of their vasculature is compromised.^[19] GULO^–/– mice have been used as a human model in multiple subsequent studies.^[20]

There have been successful attempts to activate lost enzymatic function in different animal species.^{[21][22][23][24]} Various GULO mutants were also identified.^[25][26]

Plant models

In plants, the importance of vitamin C in regulating whole plant morphology, cell structure, and plant development has been clearly established via characterization of low vitamin C mutants of Arabidopsis thaliana, potato, tobacco, tomato, and rice. Elevating vitamin C content by overexpressing inositol oxygenase and gulono-1,4-lactone oxidase in A. thaliana leads to enhanced biomass and tolerance to abiotic stresses.^[27][28]

Alternative substrates and related enzymes

GULO belongs to a family of sugar-1,4-lactone oxidases, which also contains the yeast enzyme D-arabinono-1,4-lactone oxidase (ALO). ALO produces erythorbic acid when acting on its canonical substrate. This family is in turn a subfamily under more sugar-1,4-lactone oxidases, which also includes the bacterial L-gulono-1,4-lactone dehydrogenase and the plant galactonolactone dehydrogenase.^[29] All these aldonolactone oxidoreductases play a role in some form of vitamin C synthesis, and some (including GULO and ALO) accept substrates of other members.^[30]

See also

• Vitamin C (ascorbic acid)
• Oxidoreductase
• Scurvy

References