Acids pantothenic

Pantothenic acid has a central role in energy-yielding metabolism as the functional moiety of coenzyme A (CoA), in the biosynthesis of fatty acids as the prosthetic group of acyl carrier protein, and through its role in CoA in the mitochondrial elongation of fatty acids the biosynthesis of steroids, porphyrins, and acetylcholine and other acyl transfer reactions, including postsynthetic acylation of proteins. Perhaps 4% of all known enzymes utilize CoA derivatives. CoA is also bound by disulfide links to protein cysteine residues in sporulating bacteria, where it may be involved with heat resistance of the spores, and in mitochondrial proteins, where it seems to be involved in the assembly of active cytochrome c oxidase and ATP synthetase complexes. 

Pantothenic acid is widely distributed in all foodstuffs. The name is derived from the Greek for from everywhere, as opposed to other vitamins that were originally isolated from individual rich sources. 

Deficiency is well documented in chickens, which develop a pantothenic acid-responsive dermatitis. Other experimental animals show a variety of abnormalities from pantothenic acid deficiency. In human beings dietary deficiency has not been reliably documented, although it has been implicated in the burning foot syndrome (nutritional melalgia). Subjects maintained on pantothenic acid-deficient diets or given the antagonist w-methyl pantothenate develop relatively unspecific symptoms that respond to repletion with the vitamin. 

Pantothenic acid is a water-soluble vitamin. The vitamin has two functions, in the biosynthesis of coenzyme A and in the synthesis of the cofactor of fatty acid 

FIGURE 9.75 Results of the FAD sHmuJation test used to assess vitamin status in high school Students. (Redrawn with permission from Sauberlich el a ., 1972.) 

The average intake of pantothenic add, as free pantothenic add and as coenzyme A, acetyl-ooenzyme A, and long-chain fatty acyl-cocnzyme A, is S to 10 mg/day. An RDA for the vitamin has not been established because the vitamin is plentiful in a variety of foods. Pantothenic acid is present in all plant and animal foods. The richest sources of the vitamin are liver, yeast, egg yolk, and vegetables. In foods, the vitamin occurs mainly as coenzyme A, 

FIGURE 9,76 Digestion of dietary coenzyme A with the release of paruothenic acid- 

Covniyme A 3, 5 -Ad4no)ine diptwaphstv FtGURl 9.7S Conversion of fatty add synthase to the holoenzyme form. 

Pantothenic acid is one of the three substrates needed to synthesise coenzyme A. It is phosphory-lated to 4 -phosphopantothenic acid by the action of pantothenate kinase (Abiko et al. 1972). The formation of 4 -phosphopantetheine is a two-step process in which 4 -phosphopantofhenic acid and l-cysteine are first converted to 4 -phosphopantothen- 

Daily intraperitoneal administration of pantothenic acid (100 mg/kg) for 5 days conferred significant protection against the peroxidative actions of a 0.5 ml/kg intraperitoneal dose of CCh in rats (Nagiel-Ostaszewski and Lau-Cam 1990). lipid peroxidation by incubation of Ehrlich ascites tumour cells with FeClj -i- HjOj was partly prevented by preincubation with D-pantothenate, 4 -phospho-pantothenate, D-pantothenol, or pantethine (Sly-SHENOv et al. 1995). Rats exposed to y radiation from a Co source, receiving 0.25 Gy at weekly intervals were protected from the deleterious effects by 26 mg pantothenol/kg x day given for 2 d before each irradiation (Slyshenov et al. 1998). 

Homopantothenic acid, which is not a coenzyme A precursor, did not exert a protective effect against reactive oxygen species (Slyshenov et al. 1995). Slyshenov et al. (1995, 1995, 1998, 1999) therefore proposed that the observed protective effects of pantothenic acid and some of its derivatives against cell and tissue injury may be due to stimulation of biosynthesis of coenzyme A and glutathione. 

From the two optically active isomers of pantothenic acid (molecular weight 219.2 daltons) only the dextrorotatory form is effective as a vitamin. The free acid is a 

Knowledge of the existence and nature of pantothenic acid mainly developed in connection with microorganisms, and is more recent than that of the biological properties of nicotinamide (125). In contrast to the account given of nicotinamide derivatives, more is known in the case of pantothenate of its metabolism in bacteria, but much less of the manner of its functioning. 

ACP play critical roles in many cellular processes and essential reactions, such as energy metabolism and fatty acid synthesis. 

Currently, (J )-pantothenic acid is industrially produced by conventional chemical synthesis and marketed as the calcium salt (calpan). The global market of calpan was valued at approximately 75 million US dollars in sales in 2005 with a world output over 10 000 ton. The key starting material for large-scale chemical processes is (J )-pantolactone. This molecule can be coupled with either calcium P-alanine to form (J )-pantothenate or with 3-aminopropanol to form panthenol, an important ingredient in skin and hair care consumer products. Purification of (7 )-pantolactone from racemic mixtures occurs by chemical or enzymatic racemic resolution [320, 321]. 

Significant HMBPA accumulation indicates a metabolic bottleneck at the PanB-catalyzed hydroxymethylation step. Engineering the supply chain for methylene tetrahydrofolate, the cosubstrate of the PanB reaction, by overexpression of SerA and GlyA or of the enzymes of the glycine cleavage cycle drastically reduced HMBPA accumulation in favor of further increased (7 )-pantothenic acid production [177]. This result indicates that insufficient availability of the PanB cosubstrate is a major cause of unwanted side-product formation. 

In conclusion, the engineering of the (I )-pantothenate biosynthetic genes provided strains yielding rather high concentrations of vitamin B5 in fed-batch fermentation runs. With the performance levels reported, a superior microbial process for pantothenic acid production is coming up on the horizon. 

After a full stmctural elucidation of coen2yme A ia 1953 by Baddiley, it became evident that pantothenic acid is one of the components of coen2yme A (2) 

Biosynthesis of coen2yme A (CoA) ia mammalian cells incorporates pantothenic acid. Coen2yme A, an acyl group carrier, is a cofactor for various en2ymatic reactions and serves as either a hydrogen donor or an acceptor. Pantothenic acid is also a stmctural component of acyl carrier protein (AGP). AGP is an essential component of the fatty acid synthetase complex, and is therefore requited for fatty acid synthesis. Free pantothenic acid is isolated from hver, and is a pale yeUow, viscous, and hygroscopic oil. 

Relatively Httie is known about the bioavailabiUty of pantothenic acid in human beings, and only approximately 50% of pantothenic acid present in the diet is actually absorbed (10). Liver, adrenal glands, kidneys, brain, and testes contain high concentrations of pantothenic acid. In healthy adults, the total amount of pantothenic acid present in whole blood is estimated to be 1 mg/L. A significant (2—7 mg/d) difference is observed among different age-group individuals with respect to pantothenic acid intake and urinary excretion, indicating differences in the rate of metaboHsm of pantothenic acid. 

Panthenol (4) is the reduced form of pantothenic acid and is the pure form most commonly used. The alcohol is more easily absorbed and is converted iato the acid m vivo (12). Both panthenol and pantyl ether are used ia hair care products. 

Kirk-Othmer Encyclopedia of Chemical Technology (4th Edition) 

The major industrial route to calcium pantothenate starts from isobutyralde-hyde, which is condensed with formaldehyde. Hydrocyanation and hydrolysis affords the racemic pantolactone (Fig. 8.20). The resolution of pantolactone is carried out by diastereomeric crystallization with a chiral amine, such as (+)-2-aminopinane (BASF), 2-benzylamino-l-phenylethanol (Fuji) or (lR)-3-endo-ami-nonorbomeol (Roche). The undesired enantiomer is racemized and recycled. 

The reaction of (R)-pantolactone with calcium 3-aminopropionate (synthesized from acrylonitrile, see Fig. 8.20) affords calcium pantothenate [111]. 

The diastereomeric crystallization of pantolactone is laborious due to the need to recycle the resolving agent. Various schemes to replace this latter step with the chemical or microbial oxidation of pantolactone, followed by microbial reduction to the (R)-enantiomer, were unsuccessful because the productivity of the microbial step remained too low [110 a]. 

The enantioselective hydrolysis of pantolactone into (R)-pantoic acid and (S)-pantolactone (Fig. 8.21), in the presence of (R)-pantolactone hydrolase from Fu-sarium oxysporum [110b], offers a better alternative. An alginate-entrapped 

The biosynthesis of (R)-pantothenate in E. coli [112] (see Fig. 8.22) and Coryne-hactcrium glutamicum [113] has been elucidated. 3-Methyl-2-oxobutyrate, an intermediate in the L-Val biosynthesis pathway, is successively hydroxymethylated and reduced to (R)-pantoate. The latter intermediate is coupled, in an ATP-re-quiring reaction, with 3-aminopropionate that is derived from L-aspartate via decarboxylation. The corresponding genes have been identified [114]. 

Vitamin Source Chromato- graphic mode Reference 

Heroff, J.C. (1979) In Uquid Chromatographic Analysis of Food and Beverages, Vol. 2. Academic Press, New York, NV. 

Plasma NPC Kimura, M., Fujita, T. and Itokawa, Y. (1982) Clin. Chem. 28. 29-31. 

Chemical synthesis RPC Nielsen, P., Rauschenbach, R. and Bacher, A. (1983) Anal. Biochem. 130, 359-368. 

---

Species A, RE 6 12 C Thiamine Riboflavin Nicotinic acid Pantothenic acid Biotin Fohc acid... 

Sulfur is part of several vitamins and co-factors, eg, thiamin, pantothenic acid [79-83-4] biotin [58-85-5] and Hpoic acid. Mucopolysaccharides, eg. 

The nicotinic acid content of several nuts has been reported (in mg/kg) as follows chestnut, 200 ha2el nut, 600 almond, 1600 and sunflower seed, 5000 (40). The results of analyses for pantothenic acid are (in mg/kg) ha2el nut, 380 almond, 75 sunflower seed, 620 and walnut, 600. Nuts also contain more biotin than most fmits and vegetables. 

Niacin, nicotinamide, and nicotinic acid. Pantothenic acid,... 

Because there is less information upon which to base dietary allowances for biotin and pantothenic acid, ranges of intake are provided, as in Table 8. 

R)-Pantothenic acid (1) contains two subunits, (R)-pantoic acid and P-alanine. The chemical abstract name is A/-(2,4-dihydroxy-3,3-dimethyl-l-oxobutyl)-P-alanine (11). Only (R)-pantothenic acid is biologically active. Pantothenic acid is unstable under alkaline or acidic conditions, but is stable under neutral conditions. Pantothenic acid is extremely hygroscopic, and there are stabiUty problems associated with the sodium salt of pantothenic acid. The major commercial source of this vitamin is thus the stable calcium salt (3) (calcium pantothenate). 

Table 1. Physical Properties of Pantothenic Acid and Derivatives...

---