Ascorbate norepinephrine synthesis

WLmalasena, K., Herman, H. H., and May, S. W. (1989). Effects of dopamine p-monooxy-genase substrate analogues on ascorbate levels and norepinephrine synthesis in adrenal chromaffin granule ghosts. /. Biol. Chem. 264,124-130. 

Ascorbic acid s chemical structure makes it an electron donor and therefore a reducing agent. AA has thus been involved in two different biochemical functions redox/ antioxidant properties and enzymatic cofactor. AA has been demonstrated to be an electron donor for different enzymes. Among these enzymes, three are involved in collagen hydroxylation (Bates et al., 1972 Levene et al., 1972). Two are involved in carnitine synthesis (Nelson et al., 1981 Dunn et al., 1984). The remaining are respectively involved in norepinephrine synthesis (Kuo, 1979) and tyrosine synthesis (La Duand Zannoni, 1964). Deficiency in AA has thus been associated with extracellular matrix defects that are probably involved in vascular problems observed in scurvy. 

Little is known about how fumarate takes part in the hydroxylation reaction. Experiments with C -labeled fumarate indicate that it is not stoichiometrically converted to another compound during the reaction. Recently it has been observed that the fumarate stimulation is a function of the reducing agent concentration in the absence of ascorbate fumarate no longer stimulates norepinephrine synthesis (Levin and Kaufman, 1961). 

The adrenal gland and adrenergic neurons continue the synthesis by hydroxylating dopamine into norepinephrine (noradrenaline). Ascorbic acid (vitamin C see p.368) acts as a hydrogen-transferring coenzyme here. 

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. 

Ascorbic acid, folic acid, and vitamin Bq are cofactors in synthesis of norepinephrine from phenylalanine... 

In addition to collagen metabolism and scavenging ROS species to limit inflammation as noted above, ascorbate is required for the synthesis of norepinephrine from tyrosine, of carnitine from y-butyrobetaine whose immediate precursor is made by trimethylating lysine, for folinic acid production from folic acid. In the absence of ascorbate, the reduced activity of these processes slows nerve, energy and cardiac output, causingthe affected person to become exhausted and irritable. Scurvy is the old English word for ill-tempered. 

Ascorbate increases the activity of hydroxylases needed for the conversion of p-hydroxyphenylpyruvate to homogentisate (Chapter 17), synthesis of norepinephrine from dopamine (Chapter 32), and two reactions in carnitine synthesis (Chapter 18). It is not known whether decreased activity of these enzymes contributes to the clinical characteristics of scurvy. Although ascorbic acid is needed for maximal activity of these enzymes in vivo and in vitro, most show some activity when other reducing agents are used. 

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