Biosynthesis of Pantothenic Acid

Oxo-isovalerate may be formed by the transamination of valine it is also the immediate precursor of valine biosynthesis and an intermediate in the synthesis of leucine (both are essential amino acids in mammals). Oxo-lso-valerate undergoes a hydroxymethyl transfer reaction, in which the donor is 

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. 

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Aspartic acid decarboxylase cataly2es the decarboxylation of asparatic acid to yield P-alanine (10), a precursor for the biosynthesis of pantothenic acid (67). FiaaHy, (R)-pantothenic acid is obtaiaed by coupling P-alaniae (10) with (R)-pantoate (22) ia the presence of pantothenate synthetase ... 

Precursors in the biosynthesis of pantothenic acid include a-ketoiso valeric add (pantoic acid), uracil (/J-alanine), and aspartic acid. Intermediates in the synthesis include ketopantoic acid, pantoic acid, and -alanine. 

Jackowski S (1996) Biosynthesis of pantothenic acid and coenzyme A. In Neidhardt FC, Curtiss III R, Ingraham JL, Lin ECC, Low KB, Magasanik B, Reznikoff WS, Riley M, Schaechter M, Umbarger HE (eds) Escherichia coli and Salmonella typhimurium Cellular and Molecular Biology. Vol 1. ASM, Washington DC, p 687... 

Significant diversity exists among the CoA biosynthetic pathways of various organisms. For example, the discussions of the CoA biosynthesis enzymes above highlighted the existence in some cases of two or more distinct nonhomologous proteins that all exhibit the same activity. The transformation of ketopantoic acid 4 to pantoic acid 5 in the biosynthesis of pantothenic acid can also be catalyzed by one of the two proteins a strict KPR enzyme (the gene product EC 1.1.1.169) or the ketol-acid reductoisomerase (tfoCgene product EC... 

Brown, G.M. Biosynthesis of pantothenic acid cuid coenzyme A. In "Comprehensive Biochemistry," vol. 21 (M. Florkin and... 

Pantoyl lactone, biosynthesis of pantothenic acid from, VI, 183 Papaverine,... 

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. 

The coenzyme form of pantothenic acid is coenzyme A and is represented as CoASH. The thiol group acts as a carrier of acyl group. It is an important coenzyme involved in fatty acid oxidation, pyruvate oxidation and is also biosynthesis of terpenes. The epsilon amino group of lysine in carboxylase enzymes combines with the carboxyl carrier protein (BCCP or biocytin) and serve as an intermediate carrier of C02. Acetyl CoA pyruvate and propionyl carboxylayse require the participation of BCCP. The coenzyme form of folic acid is tetrahydro folic acid. It is associated with one carbon metabolism. The oxidised and reduced forms of lipoic acid function as coenzyme in pyruvate and a-ketoglutarate dehydrogenase complexes. The 5-deoxy adenosyl and methyl cobalamins function as coenzyme forms of vitamin B12. Methyl cobalamin is involved in the conversion of homocysteine to methionine. 

Dihydroxyacid dehydratase (E.C. 4.2.1.9) is a ubiquitous enzyme that is involved in the biosynthesis of the branched-chain amino acids (lie, Leu and Val) and of pantothenic acid and coenzyme A. The enzyme catalyzes the elimination of water from 2,3-dihydroxyalkanoic acids (23) to 2-hydroxy-2-alkenoic acids (24), which tautomerize to 2-ketoalkanoic acids (25). The enzyme from spinach has the highest activity towards 2,3-dihydroxy-3-methylbutanoic acid (Val precursor, Scheme 11.5-4) but also accepts other substrates1341. Thus, 2,3-dihydroxybutanoic acid, 3-cyclopropyl-2,3-dihydroxybutanoic add as well as 2,3-dihydroxy-3-methylpentanoic acid are substrates. With the latter substrate a slight preference for (2R,3S)-2,3-dihydroxy-... 

PanK (EC 2.7.1.33) catalyzes the first and committed step of CoA biosynthesis the ATP-dependent phosphorylation of pantothenic acid 2 to form 4 -phosphopantothenate 8 (Equation (1)). 

G. M. Brown J. M. Williamson, Biosynthesis of Folic Acid, Riboflavin, Thiamine, and Pantothenic Acid. In Escherichia coli and Salmonella typhimurium Cellular and Molecular Biology F. C. Neidhardt, J. L. Ingraham, K. B. Low, B. Magasanik,... 

The biosynthesis of coenzyme A (CoA) starts with the phosphorylation of pantothenic acid. 

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. 

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