Ascorbic synthesis

The ability to synthesise ascorbic acid from glucose is absent in a small group of animal species that include man, primates, the guinea pig and the fruit-bat this is due to the absence of the gene that codes for one of the enzymes required for ascorbate synthesis. These species are therefore dependent on an external source of the vitamin in their diet and it is needed as a cofactor for several hydroxylase enzymes, notably the iron-dependent proline and lysine hydroxylases and the copper-dependent dopamine-(3-hydroxylase the function of ascorbate in these enzymes is likely to be its ability to keep the metal in the reduced form which is necessary for hydroxylation. The ability of ascorbate to reduce Fe3+ to Fe2+ is important in promoting the gastrointestinal uptake of iron and for its release from the iron store ferritin. 

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. 

De Gara, L., de Pinto, M. C., and Arrigoni, O., 1997, Ascorbate synthesis and ascorbate peroxidase activity during the early stage of wheat development. Physiol. Plant. 100 894n900. 

D-mannose and L-galactose are efficient precursors for ascorbate synthesis, that proceeds through a pathway involving GDP-D-mannose, GDP-L-galactose, L-galactose, and L-galac-tono-1,4-lactone [223],... 

The RDA for ascorbate (Appendix IV) is the amount needed to cure or prevent scurvy while allowing adequate body reserves. However, rates of ascorbate synthesis in animals and the amounts needed to maintain serum... 

A very marked stimulation of ascorbate synthesis in rats and mice can be evoked by exposure to various noxious compounds including the carcinogenic hydrocarbons, with methylcholanthrene the most powerful (40, 47, 80, 323). 

Anderson S, Marks CB, Lararus R, Miller J, Stafford K, Seymour J, Light D, Rastetter W, Escell D. Production of 2-keto-L guloirate, an intermediate in L-ascorbate synthesis, by a genetically modified ErwiTiia herbicola. Science 1985 230 144-149. 

Barbiturate, AIA, drugs, chloretone, benzpyrene Glucose-6-P-pentose-P Glucose-6-P dehydrogenase (nonmicrosomal), UDP-transglucuronidase (microsomal). Limiting enzymes for ascorbate synthesis ... 

The main metabolic pathways of ascorbate synthesis, redox chemistry, and catabolism are summarized in Fig. 4. Ascorbate is synthesized from D-glucuronic acid in three steps D-glucuronic acid is reduced to L-gulonic acid, which is epi-... 

FIGURE 4. Ascorbate metabolism. Main pathways of ascorbate synthesis, antioxidant action, reductive recycling, and catabolism. DHA = dehydroascorbate, R = free radical, 1 = L-gulonolactone oxidase, 2 = DHA reductase, 3 = AFR reductase. Steps 2 and 3 could also occur by nonenzymatic reaction. 

Early literature demonstrated that the administration of various drugs to rats stimulated ascorbic acid synthesis, as evidenced by the dramatic increases in urinary ascorbate (Longenecker et al., 1940) and the doubling of body pools (Conney et al., 1961). Drug-induced ascorbate synthesis appeared to proceed through the glu-... 

Although age is not a disorder by itself, it has been associated with several diseases. Old human subjects require more AA in their diet than do young subjects to reach a desired plasma ascorbate concentration (Lykkesfeldt et al., 1998). Animal studies have revealed a diminished expression of SVCTl mRNA and a decline in the capacity of cells to absorb AA during aging (Michels et al., 2003). The ascorbate concentration in the liver of male rats decreases with age even though the rate of de novo ascorbate synthesis does not. When incubated with ascorbate, isolated hepatocytes from old as compared with young rats show decreased maximal rate of ascorbate uptake and lower steady state intracellular ascorbate concentration. 

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