The ability to synthesize ascorbic acid is absent in the insects, invertebrates, and fishes. The biosynthetic capacity started in the kidney of amphibians, resided in the kidney of reptiles, became transferred to the liver of mammals, and finally disappeared from the guinea pig, the flying mammals, monkey, and man. A similar transition in the biosynthetic ability was observed in the branched evolution of the birds.

https://science.sciencemag.org/content/sci/182/4118/1271.full.pdf

Evolution and the biosynthesis of ascorbic acid

The requirement of ascorbic acid (vitamin C ) is a common property of living organisms, and it has long been considered that all animals except the guinea pig, monkey, and man can synthesize this vitamin. The classic method for determining the ability of an animal to synthesize ascorbic acid is to feed it a scorbutogenic diet for a prolonged period and to observe the appearance of the scurvy syndrome. Obviously, the method is laborious and time-consuming. Also, the onset of the scorbutic syndrome depends on the ascorbic-acid-retention capacity of the animal. For example, whereas the guinea pigs can be made scorbutic in about 3 weeks, it takes 3 to 4 months to produce scurvy in man. Since the discovery of the technique for studying ascorbic acid synthesir in vitro,1-8 the task has become much simpler. In this technique, the tissue homogenates or the subcellular fractions are incubated with precursors of ascorbic acid and the amount of the vitamin formed is estimated. Using the in vitro method, we have examined the ascorbic acid synthesizing abilities of different species of animals in the phylogenetic tree, and the results are given below.

Synthesis and some major functions of vitamin C in animals.

Nucleotide Activation of Liver Microsomal Glucuronidation

Biosynthesis of L-ascorbate (vitamin C) occurs by different pathways in plants and mammals. Yeast contain D-erythroascorbate, a C5 analog of ascorbate. UDP-D-glucuronic acid is the precursor in mammals. Loss of UDP forms glucuronic acid/glucuronolactone. Reduction of these at C-1 then forms L-gulonic acid/L-gulono-1,4-lactone. The lactone is oxidized by a microsomal L-gulono-1,4-lactone oxidase to ascorbate. Only the L-gulono-1,4-lactone oxidase has been purified and cloned, and very little is known about the properties of the other enzymes. Plants form ascorbate from GDP-D-mannose via GDP-L-galactose, L-galactose, and L-galactono-1,4-lactone. The final oxidation of L-galactono-1,4-lactone to ascorbate is catalyzed by a mitochondrial L-galactono-1,4-lactone dehydrogenase located on the inner membrane and using cytochrome c as electron acceptor. GDP-mannose pyrophosphorylase and L-galactono-1,4-lactone dehydrogenase have been cloned. Yeast synthesizes D-erythroascorbate from D-arabinose and D-arabinono-1,4-lactone in a pathway analogous to that in plants. The plant, mammalian, and yeast aldonolactone oxidase/dehydrogenases that catalyze the last step in each pathway have significant sequence homology. L-Gulono-1,4-lactone oxidase is mutated and not expressed in animals, such as primates, that have lost ascorbate biosynthesis capacity. Assessment of the literature reveals that little is known about many of the enzymes involved in ascorbate biosynthesis or about the factors controlling flux through the pathways. There is also a possibility that minor alternative pathways exist in plants and mammals.

L-ascorbic acid biosynthesis.

Publisher Summary This chapter discusses ascorbic acid in endocrine systems. Ascorbic acid is found in highest concentration in certain endocrine tissues of almost all mammals. Overviews of the chemistry of ascorbic acid and of methods for its detection are essential for understanding ascorbic acid in biological systems. Appreciation of basic ascorbate chemistry suggests functions for ascorbate in endocrine tissues. Knowledge of the difficulties with older ascorbate assays may help to explain why formulations for ascorbate function are just emerging now. The earliest physicians did not know what ascorbic acid was, but they clearly were familiar with the end results of lack of ascorbate in the diet. The first chemically stable product in the oxidation of ascorbic acid is dehydroascorbate. For a basic understanding of the dehydroascorbate/ascorbate redox pair, it is easiest to conceptualize the two species as existing under some equilibrium. The conditions of the equilibrium are influenced not only by the original concentrations of the two species but by light, pH, and possibly temperature.

Ascorbic acid in endocrine systems.

In exploring the mechanism of biosynthesis of ascorbic acid by the rat, King and his coworkers (Musulin, Tully, Longenecker & King, 1939; Longenecker, Musulin, Tully & King, 1939; Longenecker, Fricke & King, 1940) observed that rats treated with Chloretone (1:1:1-trichloro-2methylpropan-2-ol) excreted more ascorbic acid than did the controls. By employing Chloretonized rats and isotopically labelled precursors they (Jackel, Mosbach, Burns & King, 1950; Horowitz, Doerschuk & King, 1952; Horowitz & King, 1953a, b) presented evidence for the following route of the synthesis: D-Glucose -+ D-glucurono-y-lactone -* L-ascorbic acid. Subsequently, Isherwood, Chen & Mapson (1954) and Mapson, Isherwood & Chen (1954) came to the conclusion from an extensive series of experiments that in plant and animal systems respectively the following sequences were involved: (1) D-Galactose -+ D-galacturonic acid methyl ester -+ L-galactono-y-lactone -+ L-ascorbic acid. (2) D-Glucose -+ D-glucurono-y-lactone -+ Lgulono-y-lactone --. L-ascorbic acid. Hassan & Lehninger (1956) reported that ratliver extracts containing the microsomes and soluble supernatant could convert D-glucuronolactone, L-gulonolactone and also the corresponding free acids into L-ascorbic acid in the presence of cofactors. In experiments previously carried out in this Laboratory it had been observed that rat-liver tissue incubated with sodium pyruvate showed a higher ascorbic acid value than did the controls incubated without the substrate (Roy, Roy & Guha, 1946). But in no experiment was the value so obtained higher than the original ascorbic acid content of the tissue before incubation, and it was possible therefore that pyruvic acid was not a direct precursor. In a search for a system in which a net synthesis over and above the original tissue ascorbic acid level takes place, Chatterjee, Ghosh, Ghosh & Guha (1957a) found, in later experiments, that a marked synthesis of ascorbic acid occurred in homogenates of rat-liver tissue, containing potassium cyanide, from D-glucurono-ylactone, the increase in ascorbic acid value being sometimes two to three times that originally present. No other substrate, including sodium Dglucuronate and sodium pyruvate, could be so converted into ascorbic acid. Subsequently, it was observed that L-gulonolactone, but not sodium L-gulonate, could also act as the substrate and this conversion took place in the absence of cyanide. Liver tissues of all the mammals investigated could bring about this cyanide-stimulated synthesis, but homogenates of the brain (rat), kidney (rat and goat) or adrenal gland (cow) were ineffective in this respect. Extracts from cow and goat livers were found to be the most active, and goat liver, being more freshly available, was chosen for further studies on the enzyme system concemed. The enzyme system was separated from goat-liver homogenates and obtained in the microsomes and the soluble fraction; it could be further concentrated from the extract by precipitation with ammonium sulphate (Chatterjee, Ghosh, Ghosh & Guha, 1958a). The present paper deals with detailed studies of this enzyme preparation.

Effect of cyanide on the biosynthesis of ascorbic acid by an enzyme preparation from goat-liver tissue.

http://science.sciencemag.org/content/sci/126/3274/608.full.pdf

B. C. Guha

Papers

Effect of cyanide on the biosynthesis of ascorbic acid by an enzyme preparation from goat-liver tissue.

Effect of cyanide on biosynthesis of ascorbic acid in vitro.