Pantothenic Acid Pantoyl--Alanine

Pellagra-like symptoms can occur in Hartnup s disease and carcinoid syndrome. Hartnup s disease is an inherited disorder of amino acid transport (Chapter 17) in which niacin deficiency presumably develops because niacin intake is inadequate to supply metabolic needs when combined with the decreased absorption of dietary tryptophan. In carcinoid syndrome, up to 60% of available dietary tryptophan is diverted to formation of 5-hydroxytryptamine (serotonin) by what is normally a minor pathway. 

Pantothenic acid is ubiquitous in plant and animal tissues and especially abundant in foods rich in other B vitamins. No RDA has been established, but a daily intake of 5-10 mg is thought to be adequate for adults. Deficiency in humans is unknown. 

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Pantothenic acid (pantoyl-(3-alanine) is another amino-acid derivative that is required by bacteria and pantoyltaurine is an antimetabolite. Unfortunately, pantothenic acid is also required by humans so the possibility of the development of a drug from this growth factor is severely limited. 

A pantothenic acid hydrolase (pantothenase) activity has been isolated from Pseudomonas fluorescens and other Pseudomonas strains. This enzyme hydrolyzes the amide bond of pantothenic acid 2 to form pantoic acid 5 (or pantoyl lactone) and /i-alanine 7 (EC 3.5.1.22) (Equation (10)). A detailed kinetic study of the reaction mechanism has shown that the reaction is partially reversible because of the formation of an acyl—enzyme (pantoyl-enzyme) intermediate during the course of catalysis, which may react with either water or / -alanine to form pantoic acid (the product hydrolysis) or pantothenic acid (the original substrate) Such a mechanism suggests that this enzyme could act as a pantothenate synthase, as reaction of the active site serine with pantoyl lactone would result in the formation of the pantoyl—enzyme intermediate. However, no biochemical or genetic evidence is currently available to support such a hypothesis. 

Pantothenic acid [A(-((/ )-2,4-dihydroxy-3,3-dime-thylbutyl)-/S-alanine, D-pantoyl-/3-alanine, vitamin Bj, vitamin B5]. 

Pantothenic acid is a yellowish viscous oily liquid, which is readily soluble in water, alcohols, and dioxane, slightly soluble in diethyl ether and acetone, and virtually insoluble in benzene and chloroform. The stability of pantothenic acid in aqueous solutions is very pH dependent. It is most stable in slightly acidic medium (pH 4 to 5). Both in acidic and alkaline media it is hydrolytically cleaved to yield pantoic acid and its salts, respectively, and P-alanine. In acidic solutions, pantoic acid spontaneously eliminates one molecule of water, forming R)-2-hydroxy-3,3-dimethyl-4-butanolide (a-hydroxy-P,P-dimethyl-y-butyrolactone), referred to as pantoyl lactone or pantolactone (Fig. 4). 

Active formaldehyde (hydroxymethyltetrahydrofolic acid, cf. Chapt. VI-5) is attached to a-keto-isovaleric acid (arising from valine by transamination) reduction of the keto group affords pantoic acid. ATP activates the carboxyl group, and the resulting pantoyl-AMP compound condenses with 3-alanine to yield pantothenic acid. 

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