Ascorbic acid cofactors

Folding paperboard food cartons, 25 36 Folex, 13 43t, 52-53 Folic acid, 2 822 27 655 25 800-803 ascorbic acid and, 25 769 cofactor forms of, 25 801-802 dietary sources of, 25 803 drug-nutrient interactions involving, 25 802-803... 

Group-transfer reactions often involve vitamins3, which humans need to have in then-diet, since we are incapable of realizing their synthesis. These include nicotinamide (derived from the vitamin nicotinic acid) and riboflavin (vitamin B2) derivatives, required for electron transfer reactions, biotin for the transfer of C02, pantothenate for acyl group transfer, thiamine (vitamin as thiamine pyrophosphate) for transfer of aldehyde groups and folic acid (as tetrahydrofolate) for exchange of one-carbon fragments. Lipoic acid (not a vitamin) is both an acyl and an electron carrier. In addition, vitamins such as pyridoxine (vitamin B6, as pyridoxal phosphate), vitamin B12 and vitamin C (ascorbic acid) participate as cofactors in an important number of metabolic reactions. 

Vitamin C, ascorbic acid, is required as a cofactor for the enzyme prolyl hydroxylase, which catalyzes the formation ofhydroxyproiine during collagen biosynthesis. 

Ascorbic acid or vitamin C is found in fruits, especially citrus fruits, and in fresh vegetables. Man is one of the few mammals unable to manufacture vitamin C in the liver. It is essential for the formation of collagen as it is a cofactor for the conversion of proline and lysine residues to hydroxyproline and hydroxylysine. It is also a cofactor for carnitine synthesis, for the conversion of folic acid to folinic acid and for the hydroxylation of dopamine to form norepinephrine. Being a lactone with two hydroxyl groups which can be oxidized to two keto groups forming dehydroascorbic acid, ascorbic acid is also an anti-oxidant. By reducing ferric iron to the ferrous state in the stomach, ascorbic acid promotes iron absorption. 

All the internal monooxygenases that have so far been purified and characterized contain flavin coenzymes. The external hydrogen donors include reduced NAD, reduced NADP, ascorbic acid and sulfhydryl compounds. Cofactors required for the external monooxygenases are flavin, pteridine, copper, nonheme iron and heme as cytochrome P-450. In some monooxygenase reactions, enzymes and/or electron carrier systems other than monooxygenase itself are involved in the transfer of an electron or hydrogen from the external hydrogen donor to the cofactor involved. 

Hydroxyproline and hydroxylysine result from the hydroxylation by specific hydroxylases of proline and lysine residues after their incorporation into a-chains. The enzymes require ascorbic acid as a cofactor. [Note An ascorbic acid deficiency results in scurvy.] The hydroxyl group of the hydroxylysine residues of collagen may be enzymatically glycosy lated (most commonly, glucose and galactose are added sequentially to the triple helix). 

Vitamin C (ascorbic acid) functions as an antioxidant and as a cofactor for hydroxyla tion reactions in procollagen. A deficiency of vitamin C results in scurvy, a disease char acterized by sore, spongy gums, loose teeth, and poor wound healing. There is no known toxicity for this vitamin. 

Ascorbic acid, folic acid, and vitamins Bf1, and B 2 are cofactors in synthesis of epinephrine from phenylalanine... 

Ascorbic Acid Is Required to Maintain the Enzyme that Forms Hydroxyproline Residues in Collagen Vitamin B12 Coenzymes Are Associated with Rearrangements on Adjacent Carbon Atoms Iron-Containing Coenzymes Are Frequently Involved in Redox Reactions Metal Cofactors Lipid-Soluble Vitamins... 

Vitamin C [ascorbic acid) Men 90 mg/d Women 75 mg/d Cofactor for reactions requiring reduced copper or iron met-alloenzyme and as a protective antioxidant prevents scurvy Gastrointestinal disturbances, kidney stones, excess iron absorption... 

Much of the work on model systems was stimulated by the observation of Udenfriend and co-workers in 19546S4a,b that a mixture of Fe(II), EDTA, ascorbic acid, and molecular oxygen could hydroxylate arenes to phenols under mild conditions. Udenfriend s reagent also hydroxylates alkanes to alcohols and epoxidizes olefins.670 6 74 The EDTA in Udenfriend s reagent probably reduces the redox potential of the Fe(II)/Fe(III) couple. The ascorbic acid functions as an electron donor, analogous to the cofactor in monooxygenases, and can be replaced by other enediols.672... 

Additional errors of phenylalanine and tyrosine metabolism include tyrosinosis, or hereditary tyrosinemia, neonatal tyrosinemia, and alcaptonuria. In the first case, there is a probable defect in p-hydroxyphenylpyruvate oxidase. In neonatal tyrosinemia, the problem is transient and may be solved by the administration of ascorbic acid. Ascorbic acid is apparently a cofactor for p-hydroxy-phenylpyruvate oxidase. Alcaptonuria is a benign disorder in which homogen-tisic acid oxidase is inoperative and homogentisic acid is excreted in the urine. Air oxidizes the homogentisic acid to a pigment, giving urine a black color. This pigment also accumulates in the patient s tissues. 

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. 

A procollagen triple helix is assembled in the endoplasmic reticulum helix formation is aided by disulfide bonds between N- and C-terminal propeptides, which align the polypeptide chains. Post-translational modification of procollagen is crucial in allowing for collagen fibril formation. For example, in cells deprived of ascorbate, as in the disease scurvy, the procollagen chains are not hydroxylated sufficiently to form stable triple helices at normal body temperature (hydrox-ylation is through the activity of prolyl hydroxylase, which requires the cofactor ascorbic acid). 

D-lso-ascorbic acid (erythorbic acid see Figure 13.1) also has vitamin activity. in vivo and in cell culmre, it has only about 5% of the biological activity of ascorbate, but this seems to be from poor intestinal absorption and tissue uptake. In vitro with purified enzymes, it has the same cofactor activity as ascorbate. Although it is not a namrally occurring compound, erythorbic acid is widely used interchangeably with ascorbic acid, in cured meats and as an antioxidant in a variety of foods. 

Menniti FS, Knoth J, and Diliberto EJ Jr (1986) Role of ascorbic acid in dopamine beta-hydroxylation. The endogenous enzyme cofactor and putative electron donor for cofactor regeneration./oMmfl/ of Biological Chemistry 2S, 16901-8. 

---