Vitamin pantothenic acid

In bacteria and plants, the individual enzymes of the fatty acid synthase system are separate, and the acyl radicals are found in combination with a protein called the acyl carrier protein (ACP). However, in yeast, mammals, and birds, the synthase system is a multienzyme polypeptide complex that incorporates ACP, which takes over the role of CoA. It contains the vitamin pantothenic acid in the form of 4 -phosphopan-tetheine (Figure 45-18). The use of one multienzyme functional unit has the advantages of achieving the effect of compartmentalization of the process within the cell without the erection of permeability barriers, and synthesis of all enzymes in the complex is coordinated since it is encoded by a single gene. 

R)-(—)-Pantolactone (22), a key intermediate for the preparation of the vitamin pantothenic acid, has been obtained with high stereoselectivity (e.e. = 87 %) by the asymmetric hydrogenation of the corresponding ketopantotyllactone in the presence of a rhodium complex of BPPM (13) 54). 

FIGURE 21-4 Acyl carrier protein (ACP). The prosthetic group is 4 -phosphopantetheine, which is covalently attached to the hydroxyl group of a Ser residue in ACP. Phosphopantetheine contains the B vitamin pantothenic acid, also found in the coenzyme A molecule. Its —SH group is the site of entry of malonyl groups during fatty acid synthesis. 

Reactions of the TCA cycle Enzyme that oxidatively decarboxylates pyruvate, its coenzymes, activators, and inhibitors REACTIONS OF THE TRICARBOXYLIC ACID CYCLE (p. 107) Pyruvate is oxidatively decarboxylated by pyruvate dehydrogenase complex producing acetyl CoA, which is the major fuel for the tricarboxylic acid cycle (TCA cycle). The irreversible set of reactions catalyzed by this enzyme complex requires five coenzymes thiamine pyrophosphate, lipoic acid, coenzyme A (which contains the vitamin pantothenic acid), FAD, and NAD. The reaction is activated by NAD, coenzyme A, and pyruvate, and inhibited by ATP, acetyl CoA, and NADH. 

Figure 14-1 Coenzyme A, an acyl-activating coenzyme containing the vitamin pantothenic acid.

The most abundant amino acids are those that are protein constituents and these are always a-amino acids. However, there are many other amino acids that occur naturally in living systems that are not constituents of proteins, and are not a-amino acids. Many of these are rare, but others are common and play important roles in cellular metabolism. For example, 3-aminopropanoic acid is a precursor in the biosynthesis of the vitamin, pantothenic acid,2... 

Phosphopantetheine coenzymes are the biochemically active forms of the vitamin pantothenic acid. In figure 10.11, 4 -phosphopantetheine is shown as covalently linked to an adenylyl group in coenzyme A or it can also be linked to a protein such as a serine hydroxyl group in acyl carrier protein (ACP). It is also found bonded to proteins that catalyze the activation and polymerization of amino acids to polypeptide antibiotics. Coenzyme A was discovered, purified, and structurally characterized by Fritz Lipmann and colleagues in work for which Lipmann was awarded the Nobel Prize in 1953. 

Structures of the vitamin pantothenic acid (in red) and coenzyme A. The terminal —SH (in blue) is the reactive group in coenzyme A (CoASH). 

Rawalpally TR (1998) Vitamins (pantothenic acid). Kirk—Othmer Encyclopedia of Chemical Technology, 4th edn, Vol 25. Wiley, New York, pp 99-116. 

Some of the less common d enantiomers of amino acids are also found in nature. For example, D-glutamic acid is found in the cell walls of many bacteria, and D-serine is found in earthworms. Some naturally occurring amino acids are not a-amino acids y-Aminobutyric acid (GABA) is one of the neurotransmitters in the brain, and jS-alanine is a constituent of the vitamin pantothenic acid. 

A large number of amino acids involved in metabolism are not found in proteins e.g., /3-alanine, OOC—CH2—CH2—NH, is an intermediate in the synthesis of the B vitamin pantothenic acid, but it is not found in proteins. Although most naturally occurring amino acids are of the t. configuration, some o-amino acids arc found in certain antibiotics and in the cell walls of some bacteria. 

Pantothenic acid is well conserved over a week after the administration of tracer doses of [ C]pantothenic acid to rats, less than 40% of the dose is recovered in the urine, all as the free vitamin. Pantothenic acid filtered by the kidneys is largely resorbed by a sodium-dependent system in the renal tubule brush border membrane (Barbara and Podevin, 1986). 

Saliha Ki, Horner HA, and Kirk K (1998) Transport and metaholism of the essential vitamin pantothenic acid in human erythrocytes infected with the malaria parasite Plasmodium falciparum. Journal of Biological Chemistry 273,10190-5. 

Deficiencies of enzymes involved in the transformation of the vitamin pantothenic acid (64) into the cognate coenzyme forms (66, Fig. 7) result in severe developmental and neurological deflcits that affect few human patients (34, 72). Therapy with megadoses of pantothenic acid has been advocated, but their efficiency has yet to be demonstrated by stringent clinical studies (73). 

FIGURE 431 Coen -yfne A- The vitamin, pantothenic acid, occurs as part of the structure of coenzyme A,... 

FIGURE 6ill The sphin osine biosyntheiic pathway. As is the case for most biochemical pathways, this pathway utilizes several cofactors that are made from vitamins. The vitamins pantothenic acid, vitamin niacin, and riboflavin are used to make the cofactois iridicaied in the figure. 

Many more examples can be found in the recent literature [108]. Another esterase process is described in more detail here. It is the optical resolution of d,l-pantoyl lactone (d,l-PL) by a fungal lactonase. The D-isomer is a key component in the vitamin pantothenic acid and in coenzyme A. d,l-PL is easily produced by adding HCN to the aldol of formaldehyde and isobutanal with subsequent acidic lactonization. For commercial production of D-PL the racemate can be resolved by chiral amines. 

This enzyme contains a phosphopantetheine residue, derived from the vitamin pantothenic acid, and a cysteine residue both can form thioesters with acyl groups. The growing fatty acyl chain moves from one to the other of these sulfhydryl residues as it is elongated. 

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