Pantothenic Acid1



Pantothenic Acid1


Paula R. Trumbo





HISTORICAL OVERVIEW

Pantothenic acid belongs to the group of B vitamins. The name is a Greek derivation meaning “from everywhere.” Earlier names used for pantothenic acid include vitamin B5, chick antidermatitis factor, antidermatosis vitamin, and chick antipellagra factor. Pantothenic acid was isolated by R. J. Williams et al in 1931 (1), and this isolate was shown to be a single acidic substance essential for the growth of yeast in 1933 (2). The structure of pantothenic acid was later determined in 1939 (3). In 1940, Williams et al successfully synthesized pantothenic acid (4), thus showing its relationship with inositol, thiamin, biotin, and vitamin B6 as to the growth of yeast (5). These researchers also developed assays for the isolation and measurement of pantothenic acid (6). In 1947, Lipmann et al identified pantothenic acid as one of the components of coenzyme A (CoA). The accepted biochemical structure of CoA was published in 1953 (7). It was not until 1954 that Bean and Hodges (8) reported that pantothenic acid is essential in human nutrition. Pantothenic acid-containing CoA has since been shown to be essential to the respiratory tricarboxylic acid (TCA) cycle, fatty acid synthesis and degradation, and many other metabolic and regulatory processes.


TERMINOLOGY, CHEMISTRY, AND BIOCHEMISTRY

Pantothenic acid is water soluble, exists as a yellow viscous oil, and is unstable to acids, bases, and heat. Pantothenic acid, d(+)-α-(-dihydroxy-β,β-dimethylbutyryl-β-alanine), is synthesized by microorganisms through an amide linkage of β-alanine and pantoic acid (Fig. 25.1). Pantetheine consists of a β-mercaptoethylamine group added to pantothenate in humans. CoA is composed of 4′-phosphopantetheine linked by an anhydride bond to adenosine 5′-monophosphate, modified by a 3′-hydroxyl phosphate. In addition to serving as a component of CoA, 4′-phosphopantetheine is linked to certain proteins. 4′-Phosphopantetheine has been shown to be an essential cofactor in the biosynthesis of fatty acids (e.g., fatty acid synthetase), peptides (e.g., antibiotics), and polyketides (9).

Pantothenate, in the form of CoA, performs multiple roles in cellular metabolism. CoA facilitates the transfer of acetyl or acyl groups. β-Oxidation of fatty acids and the oxidative degradation of amino acids depend on CoA and thereby make the catabolic products available to the TCA cycle. Furthermore, acetyl CoA provides acetyl groups to oxaloacetic acid for the formation of citrate in the TCA cycle. The condensation of three acetyl CoA molecules yields 3-hydroxy-3-methylglutaryl-CoA (HMG CoA), an intermediate in cholesterol synthesis.


DIETARY SOURCES

Free and conjugated pantothenic acid is found in various plants and animals foods. Approximately 85% of dietary pantothenic acid exists as CoA or phosphopantetheine (10). Major sources of pantothenic acid include beef, chicken, liver, eggs, tomato products, broccoli, potatoes, and whole grains (11, 12) (Table 25.1). Pantothenic acid is added to various foods, such as breakfast cereals, beverages, and baby foods. Fruit products and corn-based
and presweetened cereals are among the poorest sources of pantothenic acid.

A review of studies in North America and the United Kingdom reported that the average pantothenic acid concentration in mature breast milk ranges from 2.2 to 2.5 mg/L (13). The pantothenic acid concentration in human milk has been reported to be 6.7 mg/L, with no change occurring from 1 to 6 months postpartum (14). The pantothenic acid content in human milk correlates with maternal intake of the vitamin (15). In one report, the concentration of pantothenic acid in breast milk increased from 0.48 to 2.45 mg/L within 4 days after parturition (16).








TABLE 25.1 PANTOTHENIC ACID CONTENT OF FOODS










































FOOD


PANTOTHENIC ACID (mg/100g EDIBLE PORTION)


Beef, ground, cooked


0.33


Bran, 100%


1.73


Broccoli, raw


0.53


Cashew nuts


1.22


Chicken, fried


1.00


Eggs, hard-boiled


1.40


Liver, fried


5.92


Milk, canned


0.76


Mushrooms, cooked


2.16


Potato, baked


0.86


Rice, white


1.13


Tomato products


0.75







Fig. 25.1. Coenzyme A and intermediaries.


RECOMMENDED DIETARY ALLOWANCES

In 1989, an estimated safe and adequate daily intake (ESADDI) of 4 to 7 mg/day of pantothenic acid was set because subjects were shown to excrete this level through the urine and feces (17). Based on a scientific review of the data for setting dietary reference intakes (DRIs), the determination was that the information for setting an estimated average requirement (EAR) was insufficient, and, therefore, a recommended dietary allowance (RDA) could not be set. An adequate intake (AI) value was set for pantothenic acid for all life stage and gender groups, however (Table 25.2) (18). The AI for infants 0 to 6 months old
represents the average daily intake of pantothenic acid for infants exclusively fed human milk. The AI for men and for nonpregnant and pregnant women is based on usual pantothenic acid intakes by adults in the United States. The AI for children 1 to 18 years old was set by extrapolating from the adult AI, based on body weight and growth factors. The AI during lactation is 7 mg/day because approximately 2 mg of pantothenic acid is secreted in human milk daily (18).








TABLE 25.2 ADEQUATE INTAKE FOR PANTOTHENIC ACID



































AGE (MALE AND FEMALE)


ADEQUATE INTAKE (mg/d)a


0-6 mob


1.7


7-12 mo


1.8


1-3 y


2


4-8 y


3


9-13 y


4


14-18 y


5


≥19 y


5


Pregnant women


6


Lactating women


7


a Based on usual intakes for groups 1 year old and older (see text).

b Based on the average contents of pantothenic acid in human milk consumed by infants (see text).


United States nutrition surveys do not estimate intakes of pantothenic acid. The mean pantothenic acid intake of men and women of different ages in Quebec in 1990 fell from approximately 6 to 3 mg/day with advancing age (18). The average intake of pantothenic acid was 5.5 and 4.0 g/day for the male and female population, respectively, of New Brunswick, Canada (19). Usual intakes of approximately 4 to 7 mg/day have been reported for adolescents and adults of various ages (18). The average dietary intake estimated for pregnant and lactating women has been reported at 2.8 mg/1000 kcal (20) or 7.6 mg/day for lactating women (14); for pregnant women living in Boston, the estimated intake was 6.6 mg/day (21); and for elderly persons, it was 5.9 mg/day (22). The average daily intake of pantothenic acid from multivitamin/mineral supplements has been estimated at 10 mg/day (23).


PHYSIOLOGIC ASPECTS


Digestion, Absorption, and Excretion

Dietary CoA is hydrolyzed in the intestinal lumen to dephospho-CoA, pantetheine, and phosphopantetheine. Pantetheine is further hydrolyzed by pantetheinase to pantothenic acid. Although pantothenic acid may be absorbed by passive diffusion, it is absorbed into the bloodstream of animals by a saturable, sodium-dependent active transport mechanism (24). Studies in mice indicated that the kinetics for this active transport system is not affected by variation in dietary intake levels of the vitamin (25). Although animal studies demonstrated that intestinal microflora synthesize pantothenic acid (25), the contribution to absorbed pantothenic acid in humans is unknown.

Absorbed pantothenic acid is transported by the red blood cells throughout the body (26). The vitamin is also transported in the free acid form in the plasma at a concentration of approximately 1 µg/mL (27). (The molecular weight of pantothenic acid is 219.24 g/mol; 1 mg equals 4.56 µmol; 1 µg/mL equals 4.56 µmolar [µM]). Concentrations in red blood cells are higher than in plasma. Maximum pantothenate concentrations occurred 3 minutes following intravenous injection and subsequently decreased, a finding suggesting that the vitamin is rapidly taken up by red blood cells and other tissues (28). A large increase in red blood cell pantothenate concentration was observed in men following the injection of a multivitamin mixture that included 45 mg D-panthenol (29).

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Jul 27, 2016 | Posted by in PUBLIC HEALTH AND EPIDEMIOLOGY | Comments Off on Pantothenic Acid1

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