L-gulonolactone Oxidase - Gulonolactone Oxidase Deficiency

Gulonolactone Oxidase Deficiency

The non-functional gulonolactone oxidase pseudogene (GULOP) was mapped to human chromosome 8p21 that corresponds to an evolutionarily conserved segment on either porcine chromosome 4 (SSC4) or 14 (SSC14). GULO produces the precursor to ascorbic acid, which spontaneously converts to the vitamin ("vitamin C").

The loss of activity of the gene for L-gulonolactone oxidase (GULO) has occurred separately in the history of several species. The loss of this enzyme activity is responsible for the inability of guinea pigs to enzymatically synthesize vitamin C, but this event happened independently of the loss in the haplorrhini suborder of primates, including humans. The remains of this non-functional gene with many mutations is, however, still present in the genome of the guinea pigs and in humans. 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. In addition, GULO activity has also been lost in most bats.

Loss of GULO activity in the primate order occurred about 63 million years ago, at about the time it split into the suborders haplorrhini (which lost the enzyme activity) and the more primitive strepsirrhini (which retained it). The haplorrhini ("simple nosed") primates, which cannot make vitamin C enzymatically, include the tarsiers and the simians (apes, monkeys and humans). The suborder strepsirrhini (bent or wet-nosed prosimians), which are still able to make vitamin C enzymatically, include lorises, galagos, pottos, and, to some extent, lemurs.

L-gulonolactone oxidase deficiency is called "hypoascorbemia" and is described by OMIM (Online Mendelian Inheritance in Man) as "a public inborn error of metabolism", as it affects all humans. There exists a wide discrepancy between the amounts of ascorbic acid other primates consume and what is recommended as "reference intakes" for humans. In its patently pathological form, the effects of ascorbate deficiency are manifested as scurvy.