Pantothenic acid-4-phosphate

This essential compound is universally distributed. It is formed by the joining of adenosine-3, 5-diphosphate, pantothenic acid-4 -phosphate and thioethanolamine (cysteamine). 

Coenzyme form(s). (1) Coenzyme A, composed of cysteamine, pantothenic acid, phosphate, and adenosine-3, 5 -diphosphate (2) acyl-carrier protein. 

Pantothenic acid is present in coenzyme A and acyl carrier protein, which act as carriers for acyl groups in metabolic reactions. Pyridoxine, as pyridoxal phosphate, is the coenzyme for several enzymes of amino acid metabolism, including the aminotransferases, and of glycogen phosphorylase. Biotin is the coenzyme for several carboxylase enzymes. 

BaddUey J. Thain, E.M. (1951) The Synthesis of Pantothenic Acid-2 and -4 Phosphates as Possible Degradation Products of Coenzyme A. Journal of the Chemical Society, 246-251. 

This is a complex molecule, made up of an adenine nucleotide (ADP-3 -phosphate), pantothenic acid (vitamin B5), and cysteamine (2-mercaptoethylamine), but for mechanism purposes can be thought of as a simple thiol, HSCoA. Pre-eminent amongst the biochemical thioesters is the thioester of acetic acid, acetyl-coenzyme A (acetyl-CoA). This compound plays a key role in the biosynthesis and metabolism of fatty acids (see Sections 15.4 and 15.5), as well as being a building block for the biosynthesis of a wide range of natural products, such as phenols and macrolide antibiotics (see Box 10.4). 

More recently [635], a unique extraction step in supplemented foods, by using hot water and a precipitation solution, following by HPLC-ELD/UV analysis has been performed for the simultaneous determination of pyridoxine, thiamine, riboflavin, niacin, pantothenic acid, folic acid, cyanoco-balamin, and ascorbic acid. The mobile phase consisting of phosphate buffer and methanol has been modified in order to perform ion-liquid chromatography by adding l-octanesulfonic acid sodium salt. Furthermore, triethylamine has been also added to improve peak symmetry. 

FIGURE 16-3 Coenzyme A (CoA). A hydroxyl group of pantothenic acid is joined to a modified ADP moiety by a phosphate ester bond, and its carboxyl group is attached to /3-mercaptoethylamine in amide linkage. The hydroxyl group at the 3 position of the ADP moiety has a phosphoryl group not present in free ADP. The —SH group of the mercaptoethylamine moiety forms a thioester with acetate in acetyl-coenzyme A (acetyl-CoA) (lower left). 

Folic acid and pantothenic acids maintain secretions of steroids by adrenal cortex Niacin nicotinamide adenine dinucleotide (phosphate)... 

Aspartate undergoes /3-decarboxylation to /S-alanine unlike most amino acid decarboxylases, aspartate decarboxylase is not pyridoxal phosphate-dependent, but has a catalytic pyruvate residue, derived by postsynthetic modification of a serine residue (Section 9.8.1). Pantothenic acid results from the formation of a peptide bond between /3-alanine and pantoic acid. 

The biologically active R- or 5 -pantothenic acid can be obtained upon hydrolysis of coenzyme A with a combiaation of two enzymes, alkaline phosphatase and pantotheiaase (13) (Fig. 1). The phosphatase catalyzes the selective cleavage of the phosphate bond ia coenzyme A to afford adenosin-3 5 -diphosphate (6) and 4-phosphopantetheiae (7). The latter substance is dephosphorylated enzymatically to yield pantetheiae (8), which is rapidly converted by pantotheiaase to pantothenic acid (1). Table 1 Hsts some physical properties of pantothenic acid and its derivatives. 

Caldum Pantothenate, USP. Calcium pantothenate, calcium u-pantolhenate, is a slightly hygroscopic, white, odorless, bitter powder that is stable in air. It is insoluble in alcohol and soluble 1 3 in water aqueous solutions have a pH of about 9 and lalo = -1-25 to -1-27.5 . Autoclaving calcium pantothenate at I20°C for 20 minutes may cau.se 10 to 30% decomposition. Some of the phosphates of pantothenic acid that occur naturally in coenzymes are quite stable to both acid and alkali, even on hcating. - ... 

B. The synthesis of fatty acids from glucose occurs in the cytosol, except for the mitochondrial reactions in which pyruvate is converted to citrate. Biotin is required for the conversion of pyruvate to oxaloacetate, which combines with acetyl CoA to form citrate. Biotin is also required by acetyl CoA carboxylase. Pantothenic acid is covalently bound to the fatty acid synthase complex as part of a phosphopantetheinyl residue. The growing fatty acid chain is attached to this residue during the sequence of reactions that produce palmitic acid. NADPH, produced by the malic enzyme as well as by the pentose phosphate pathway, provides reducing equivalents. Citrate, not isocitrate, is a key regulatory compound. 

Pantothenic acid is taken in as dietary CoA compounds and dCphosphopantetheine and hydrolyzed by pyrophosphatase and phosphatase in the intestinal lumen to dephospho-CoA, phosphopantetheine, and pantetheine. This is further hydrolyzed to pantethenic acid. The vitamin is primarily absorbed as pantothenic acid by a saturable process at low concentrations and by simple diffusion at higher ones. The saturable process is facilitated by a sodium-dependent multivitamin transporter, for which biotin and lipoate compete. After absorption, pantothenic acid enters the circulation and is taken up by cells in a manner similar to its intestinal adsorption. The synthesis of CoA from pantothenate is regulated by pantothenate kinase, which itself is subject to negative feedback from the products CoA and acyi-CoA. The steps involved were outlined above. Pantothenic acid is excreted in the urine after hydrolysis of CoA compounds by enzymes that cleave phosphate and the cys-teamine moieties. Only a small fraction of pantothenate is secreted into milk and even less into colostrum. 

In experimental animals, deficiency of pantothenic acid (needed for CoASH and, hence, succinyl-CoA synthesis), lack of vitamin Be, or the presence of compounds that block the functioning of pyridoxal phosphate (e.g.. 

The chemistry of the cofactors has provided a fertile area of overlap between organic chemistry and biochemistry, and the organic chemistry of the cofactors is now a thoroughly studied area. In contrast, the chemistry of cofactor biosynthesis is stiU relatively underdeveloped. In this review the biosynthesis of nicotinamide adenine dinucleotide, riboflavin, folate, molyb-dopterin, thiamin, biotin, Upoic acid, pantothenic acid, coenzyme A, S-adenosylmethionine, pyridoxal phosphate, ubiquinone and menaquinone in E. coli will be described with a focus on unsolved mechanistic problems. 

White powder. Characteristic thiol odor- May be dried in vacuo over phosphorus pentoxide at 34°. uv max 259.5 nm (e 16,800), Fairly strong acid. pK 9.6 (thiol) pK 6,4 (secondary phosphate) pK 4,0 (adenine NH3+). Soluble in water. Practically insol in ethenol, ether, acetone. Strength of solns expressed in Lipmann units (that amount of Co A which gives half-saturation of the sulfanilamide acetylation system). One unit of Co A weighs 2,43 y and contains 0,7 y pantothenic acid 1.0 mg CoA equals 413 Lipmann units. The pure dry coenzyme is bast stored in evacuated ampuls at room temp. Readily oxidized by air to the catalytically inactive disulfide. 

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