Biosynthesis of Pantothenic Acid

Plants and microorganisms are capable of the de novo synthesis of pantothenic acid from oxo-isovalerate and aspartate, by the pathway shown in Figure 12.3; animals are reliant on a preformed source 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-iso-valerate undergoes a hydroxymethyl transfer reaction, in which the donor is methylene-tetrahydrofolate, yielding oxo-pantoic acid. The hydroxymethyl-transferase is subject to feedback inhibition by pantoic acid, pantothenic acid, and CoA. Oxo-pantoate is then reduced in an NADPH-dependent reaction to pantoic acid. The reductase is reversible, but the equilibrium lies greatly in favor of pantoic acid formation.

Aspartate undergoes f-decarboxylation to f-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 f -alanine and pantoic acid.


The major functions of pantothenic acid are in CoA (Section 12.2.1) and as the prosthetic group for ACP in fatty acid synthesis (Section 12.2.3). In addition to its role in fatty acid oxidation, CoA is the major carrier of acyl groups for a wide variety of acyl transfer reactions. It is noteworthy that a wide variety of metabolic diseases in which there is defective metabolism of an acyl CoA derivative (e.g., the biotin-dependent carboxylase deficiencies; Sections and, CoA is spared by formation and excretion of acyl carnitine derivatives, possibly to such an extent that the capacity to synthesize carnitine is exceeded, resulting in functional carnitine deficiency (Section 14.1.2).

A variety of proteins are acylated by formation of thioesters to cysteine and esters to serine and threonine. Acylation may serve either to anchor the proteins in membranes (e.g., rhodopsin; Section 2.3.1) and the mannosidase of the Golgi, or to increase lipophilicity and thus enhance the solubilization of lipids being transported (e.g., the plasma apolipoproteins and milk globule proteins). Proteolipids with fatty acids esterified to threonine residues occur in the myelin sheath in nerves.

Several of the proteins of the Golgi transport system are N-acetylated at either the amino terminal or the e-amino group of a lysine residue. Acylation may be either cotranslational or posttranslational. Amino terminal acylation protects the proteins from degradation, and various acylations are required for the assembly of multisubunit membrane proteins and transport of glyco-proteins through the Golgi.

Acetyl CoA is the donor for the 7- and 9-O-acetylation of sialic acids in the Golgi membrane. Neither free acetate nor acetyl CoA crosses the Golgi membrane, and the reaction appears to be a transmembrane process, with intermediate acetylation of a membrane component that then accumulates intravesicularly. The intermediate can transfer acetyl groups onto N-acetylneuraminic acid, but not other potential acetyl acceptors.

Acetyl CoA acetyltransferase, a key enzyme of ketogenesis, and 3-oxo-acyl CoA thiolase, involved in f-oxidation, bind CoA by formation of a disulfide bond to cysteine, a reaction that can be reversed by glutathione and other sulfhydryl reagents. The physiological significance of this reaction with CoA, which inactivates the enzymes, is not clear (Quandt and Huth, 1984, 1985; Schwerdt and Huth, 1993).


Pantothenic acid is widely distributed in foods, and because it is absorbed throughout the small intestine, it is likely that intestinal bacterial synthesis also makes a contribution to pantothenic acid nutrition. As a result, deficiency has not been unequivocally reported in human beings except in specific depletion studies, which have also frequently used the antagonist «-methyl pantothenic acid.

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