Gulonolactone Oxidases

Vitamin C (Figure 45-19) is a vitamin for human beings and other primates, the guinea pig, bats, passerine birds, and most fishes and invertebrates other animals synthesize it as an intermediate in the uronic acid pathway of glucose metabohsm (Chapter 20). In those species for which it is a vitamin, there is a block in that pathway due to absence of gulonolactone oxidase. Both ascorbic acid and dehydroascorbic acid have vitamin activity. 

Vitamin C is L-ascorbic acid (chemically 2-oxogulonolactone). The two hydroxyl groups have acidic properties. By releasing a proton, ascorbic acid therefore turns into its anion, ascorbate. Humans, apes, and guinea pigs require vitamin C because they lack the enzyme L-gulonolactone oxidase (tl.3.8), which catalyzes the final step in the conversion of glucose into ascorbate. 

Until the 20th century, it was thought that scurvy was confined to humans. Most plants and animals have the ability to synthesize ascorbic acid, but it was discovered that a limited number of animals, including primates, guinea pigs, the Indian fruit bat, and trout, also lack the ability to produce ascorbic acid. In vertebrates, ascorbic acid is made in the fiver from glucose in a four-step process. Each step requires a specific enzyme and humans lack the enzyme required for the last step, gulonolactone oxidase. 

In STZ-diabetic rat livers, the levels of mRNA of 1-gulonolactone oxidase, catalase, and glutathione peroxidase were decreased at 6 weeks, as well as that of plasma alpha 1 proteinase inhibitor 3.562 AA synthesis enzyme and recycling enzyme mRNAs were also decreased, as was the level of AA itself. It seems that the antioxidative defence system had been severely damaged. 

In species for which ascorbate is not a vitamin, riboflavin deficiency can also lead to considerably reduced synthesis and low tissue concentrations of ascorbate, since gulonolactone oxidase, the key enzyme in ascorbate synthesis (Section 13.2), is a flavoprotein. 

Vitamin C is a vitamin for only a limited number of vertebrate species humans and the other primates, the guinea pig, bats, the passeriform birds, and most fishes. Most insects and invertehrates are also incapahle of ascorbate synthesis. Ascorbate is synthesized as an intermediate in the gulonolactone pathway of glucose metabolism in those vertebrate species for which ascorbate is a vitamin, one enzyme of the pathway, gulonolactone oxidase, is absent. 

Figure 13.2. Biosynthesis of ascorbate. Glucuronate reductase, EC 1.1.1.19 glucono-lactone3-lactonase, EC 3.1.1.17 gulonolactone oxidase, EC 1.1.3.8 NADPH-dependent dehydroascorbate reductase, EC 1.6.5.4 and glutathione-dependent dehydroascorbate...

Species for which ascorbate is a vitamin lack gulonolactone oxidase, and metabolize gulonic acid by reduction and decarboxylation directly to xylulose. The loss of gulonolactone oxidase seems to be the result of nonexpression of the gene rather than a gene deletion (Sato and Udenfriend, 1978). 

An autosomal recessive mutant strain of rat, which lacks gulonolactone oxidase and hence is unable to synthesize ascorbic acid, has been described (Mizushima et al., 1984). The animals have an osteogenic disorder akin to scurvy in human infants, and homozygotes are sterile. The addition of... 

Ascorbic acid is derived from glucose via the uronic acid pathway. The enzyme L-gulonolactone oxidase responsible for the conversion of gulonolactone to ascorbic acid is absent in primates, thus making ascorbic acid an essential in the diet. 

Ascorbic acid is an unusual vitamin in that it can be synthesized by most mammals however, it cannot be made by humans, primates, guinea pigs, and fruit bats. Ascorbic acid is synthesized from glucose in a six-step pathway Mammals that cannot make the vitamin lack the last enzyme of this pathway, gulonolactone oxidase. This enzyme occurs in the kidney of chickens, amphibians, and reptiles, and in the liver of most mammals (Banhegyi et at., 1997). Gulonolactone oxidase is a flavoprotein. Each catalytic event of the enzyme results in the conversion of O2 to HOOH. It might strike one as a paradox that a vitamin (vitamin C) that helps... 

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