Functions of Ascorbic Acid
Ascorbic acid, is intimately concerned, in an unknown manner, in the normal production of supporting tissues of mesenchymal origin, such as osteoid, denlin, and collagen. The outstanding chemical property of the vitamin is its reversible oxidation-reduction between ascorbic and dehydroascorbic acid. Some of the physiological properties of the vitamin must be related to this redox system although no specific coenzyme function for ascorbic acid has been demonstrated. It may help maintain the oxidation-reduction potential of cells at the proper level.
As a hydrogen acceptor it is thought to act in plants and possibly in animals in a system involving TPN and glutathione in which the metabolite passes H to TPN, and this passes hydrogen to glutathione, which may pass them on to ascorbic acid and finally to oxygen forming water:
2H from MetH2 to TPN+ to GSSG to dehydroacorbic to 02
The significance of such a proposed system in animal tissues is not yet clearly defined. Guinea pigs lose the ability to maintain normal levels of collagen as they become depleted in ascorbic acid, and the administration of the vitamin promptly corrects this defect. It was felt by Gould some years ago that ascorbic acid promotes collagen formation, in part at least through its action in bringing about hydroxyproline synthesis from proline. Collagen contains large amounts of hydroxyproline. Mitoma and Smith felt that hydroxylation of proline was not affected by ascorbic acid and that collagen synthesis and not the amino acid synthesis is at fault in the deficiency state. Gross has suggested that synthesis and breakdown of collagen may be progressing at somewhat the same rate in scorbutic guinea pigs.
Udenfriend and others more recently showed that scorbutic guinea pigs build collagentype peptides which incorporate C14-containing proline but are deficient in hydroxyproline. This hydroxyproline-deficient intermediate may require ascorbic acid for the conversion of proline already in peptide formation to hydroxyproline. The collagen intermediate may be short-lived due to its abnormal composition; it is readily attacked by collagenase. This does not establish ascorbic acid as a part of proline hydroxylase, but that may prove to be the case. The fact that the abnormal collagen may not be stable may account for the lack of new collagen formation in the scorbutic state.
Ascorbic acid or a derivative of it has been implicated in certain other hydroxylation reactions such as the hydroxylation reaction in the conversion of tryptophan to serotonin C5-hydroxytryptamine ).
The vitamin has been placed in the electron transport chain between DPNH and one of the cytochromes, a reaction that may be coupled with hydroxylation. Transport is thought to proceed from the DPNH to the active ascorbic acid derivative Cmonbdehydroascorbic acid; see further) which may be a partially oxidized radical form. This reduces the active compound to ascorbic acid, which may be oxidized to the monodehydro form by cytochrome bs' The transfer may then proceed through the other members of the transport chain to 02' The reaction product with oxygen may be the active participant in the enzymatically mediated hydroxylation. Baker and others have isolated an ascorbic acid derivative-the monodehydro-ascorbic acid in combjnation with ascorbic acid. They feel that such a complex may be the active form in hydroxylation reactions.
The foregoing scheme is not accepted by all workers in this field. In the scorbutic state .usine metabolism is abnormal. The administration of tyrosine or phenylalanine to man or lruinea pigs in the deficiency state results in the urinary excretion of p-hydroxyphenylpyruvic , and ascorbic acid medication abolishes the defect.
ormally the enzyme p-hydroxyphenylpyruvic acid oxidase mediates the oxidation of p.dro-xyphenylpyruvic acid to homogentisic acid. At one time ascorbic acid was considered to a specific cofactor for this enzyme, but a number of other compounds-some, entirely elated chemically, such as hydrocminone-were found to replace ascorbic acid in tyrosine "dation in vitro. It was later established that ascorbic acid and compounds that can replace e vitamin in vitro do so by protecting ~-hydroxyphenylpyruvic oxidase from inhibition by -- substrate, and Zannoni and LaDu have now demonstrated that ascorbic acid operates in t·o through this protection of the liver enzyme in guinea pigs.
It appears that ascorbic acid is required for tyrosine metabolism only when large amounts ~ the amino acid are ingested, and the vitamin may not be required for tyrosine metabolism der normal conditions. Ascorbic acid enhances iron absorption from the intestine in humans and animals. The mechanism probably involves the reducing property of ascorbic acid, since n in the ferrous state is prefereally absorbed.
