Gulono-1,4-lactone enzymically

Vitamin A could control differentiation by decreasing enzyme activities, by stimulating enzyme synthesis, or both. The activity of a number of enzymes (gulono-lactone oxidase, codeine demethylase, squalene cyclo-dehydrase, ATP-sulfurylase, and sulfate transferase) decreases in vitamin A-deficient animals. The significance of these observations remains obscure, and no specific coenzymic role for vitamin A has as yet been discovered. 

L-Ascorbic acid, better known as vitamin C, has the simplest chemical structure of all the vitamins (Figure 18.30). It is widely distributed in the animal and plant kingdoms, and only a few vertebrates—humans and other primates, guinea pigs, fruit-eating bats, certain birds, and some fish (rainbow trout, carp, and Coho salmon, for example)—are unable to synthesize it. In all these organisms, the inability to synthesize ascorbic acid stems from a lack of a liver enzyme, L-gulono-y-lactone oxidase. 

This enzyme [EC 1.1.1.20] catalyzes the reaction of l-gulono-1,4-lactone with NADP+ to produce D-glucur-ono-3,6-lactone and NADPH. 

It was also found that L-gulono-1,4-lactone (21) is enzymically oxidized to L-ascorbic acid (1) in 40% yield by using an enzyme system isolated from a variety of natural sources, including rat livers and germinating peas.378 L-Galactono- 1,4-lactone (16) was also oxidized to 1 with this enzyme system. 

In animals, UDP-D-glucuronic acid is the precursor it loses UDP and the D-glucuronic acid/D-glucuronolactone is reduced at C-l, forming L-gulonic acid/L-gulono-1,4-lactone. The lactone is oxidized by microsomal L-gulono-1,4-lactone oxidase to ascorbate. This enzyme is not expressed in primates, as they have lost biosynthetic capacity for ascorbate. 

Nishikimi, M., Fukuyama, R., Minoshima, S., Shimizu, N., and 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 13685-13688. 

Researchers have questioned whether the one-enzyme-deficiency theory applies to scurvy-prone animals (13). Studies showed no evidence for more than a one enzyme defect in scurvy-prone animals (14). Based on immunologic evidence of purified L-gulono-A-lactone oxidase, scurvy-prone animals do not contain immunologically cross-reacting material to gulono-A-lactone oxidase (15,16). 

This reaction is considered to be catalyzed by NADPH-dependent D-glucuronate reductase, the enzyme that acts on D-glucuronic acid in the other pathway. For the formation of L-gulono-"y-lactone, Chatterjee et al. (1961) proposed the presence of a different enzyme attacking D-glucurono-7-lactone with the requirement of cyanide, but their proposal was later challenged (Sato et al., 1976). 

Besides GLOs of animal species, the terminal enzymes of biosynthetic pathways of ascorbic acid in bakers yeast and in sweet potato were highly purified. Nishikimi et al. (1978) purified L-galactono-7-lactone oxidase from mitochondria of the yeast. This enzyme catalyzes the oxidation of L-galactono-7-lactone approximately three times as fast as that of L-gulono-7-lactone using O2 as the electron acceptor. Its molecular mass (monomer) was determined to be 56,000 daltons. Bleeg and Christensen (1982) also purified the enzyme from bakers yeast and... 

Fujitsuka, N., Yokozawa, T., Oura, H., Akao, T., Kobashi, K., lenaga, K., and Nakamura, K., 1993, L-Gulono-7-lactone oxidase is the enzyme responsible for the production of methylguanidine in the rat liver. Nephron 63 445-451. 

Nishikimi, M., Koshizaka, T., Ozawa, T., and Yagi, K., 1988b, Occurrence in humans and guinea pigs of the gene related to their missing enzyme L-gulono-y-lactone oxidase, Arch. Biochem. Biophys. 267 842-846. 

Previous studies have reported impaired urinary excretion of AA in diabetic patients (Seghieri et al., 1994 Yue et al., 1989). Further, the activity of L-gulono-gamma-lactone oxidase (GLO), a terminal enzyme of AA biosynthesis (Majumder et al., 1972) is impaired in diabetic animals, and decreased GLO activity impairs the ability to synthesize AA (Bode et al., 1993). Until recently, however, the molecular properties of the enzymes and transporters involved in AA metabolism have not been characterized, and the precise mechanisms of decreases in AA in plasma and tissues in diabetes have been undetermined. 

The vast majority of animals and plants are able to synthesize vitamin C through a sequence of four enzyme-driven steps, which convert D-glucose to vitamin C (Fig. 12.6). In eukaryotes, vitamin C biosynthesis occurs via two highly divergent biochemical pathways. In rats and other mammals, glucose is converted into L-gulono-1,4-lactone via a complex pathway involving uronic acid derivatives and... 

Sugisawa, T., Ojima, S., Matzinger, R, et al. (1995). Isolation and Characterization of a New Vitamin C Producing Enzyme (L-gulono-y-lactone Dehydrogenase) of Bacterial Origin, Biosci. 

Sugisawa T, Ojima S, Matzinger P, Hoshino T (1995) Isolation and characterization of a new vitamin C producing enzyme (L-gulono-y-lactone dehydrogenase) of bacterial origin. Biosci Biotechnol Biochem 59 190-196... 

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