Metabolic Functions of Pantothenic Acid

The major functions of pemtothenic acid eu e in CoA (Section 12.2.1) emd as the prosthetic group for AGP in fatty acid synthesis (Section 12.2.3). In addition to its role in fatty acid oxidation, CoA is the major cemier of acyl groups for a wide vmiety 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 cm boxylase deficiencies Sections 11.2.2.1 and 11.2.3.1), CoA is spared by formation and excredon of acyl carnitine derivatives, possibly to such an extent that the capacity to synthesize carnitine is exceeded, resulting in functioned ceu nitine 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 emchor the proteins in membranes (e.g., rhodopsin Section 2.3.1) emd the mannosidase of the Golgi, or to increeise lipophiUcity and thus enhemce the solubilization of lipids being transported (e.g., the plasma apolipoproteins and milk globule proteins). ProteoUpids with fatty acids esterified to threonine residues occur in the myelin sheath in nerves. 

Acetyl CoA is the donor for the 7- emd 9-O-acetylation of siedic acids in the Golgi membrane. Neither free acetate nor acetyl CoA crosses the Golgi membrane, emd the reaction appears to be a transmembreme process, with intermediate acetylation of a membreme component that then accumulates 

Several of the proteins of the Golgi transport system are iV-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 glycoproteins through the Golgi. 

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N4. Novelli, G. D., Metabolic functions of pantothenic acid. Physiol. Revs. 33, 525-543 (1953). 

The metabolic functions of pantothenic acid in human biochemistry are mediated through the synthesis of CoA. Pantothenic acid is a structural component of CoA. which is necessary for many important metabolic processes. Pantothenic acid is incorporated into CoA by a. series of five enzyme-catalyzed reactions. CoA is involved in the activation of fatty acids before oxidation, which requires ATP to form the respective fatty ocyl-CoA derivatives. Pantothenic acid aI.so participates in fatty acid oxidation in the final step, forming acetyl-CoA. Acetyl-CoA is also formed from pyruvate decarboxylation, in which CoA participates with thiamine pyrophosphate and lipoic acid, two other important coenzymes. Thiamine pyrophosphate is the actual decarboxylating coenzyme that functions with lipoic acid to form acetyidihydrolipoic acid from pyruvate decarboxylation. CoA then accepts the acetyl group from acetyidihydrolipoic acid to form acetyl-CoA. Acetyl-CoA is an acetyl donor in many processes and is the precursor in important biosyntheses (e.g.. those of fatty acids, steroids, porphyrins, and acetylcholine). 

The most important functions of pantothenic acid are its incorporation in coenzyme A and acyl carrier protein (AGP). Both CoA and AGP/4-phosphopantetheine function metabolically as carriers of acyl groups. Coenzyme A forms high-eneigy thioester bonds with carboxylic acids. The most important coenzyme is acetyl CoA. Acetic acid is produced during the metabolism of fatty acids, amino acids, or carbohydrates. The active acetate group of acetyl CoA can enter the Krebs cycle and is used in the synthesis of fatty acids or cholesterol. AGP is a component of the fatty acid synthase multienzyme complex. This complex catalyzes several reactions of fatty acid synthesis (condensation and reduction). The nature of the fatty acid synthase complex varies considerably among different species (91). 

Certain amino acids and their derivatives, although not found in proteins, nonetheless are biochemically important. A few of the more notable examples are shown in Figure 4.5. y-Aminobutyric acid, or GABA, is produced by the decarboxylation of glutamic acid and is a potent neurotransmitter. Histamine, which is synthesized by decarboxylation of histidine, and serotonin, which is derived from tryptophan, similarly function as neurotransmitters and regulators. /3-Alanine is found in nature in the peptides carnosine and anserine and is a component of pantothenic acid (a vitamin), which is a part of coenzyme A. Epinephrine (also known as adrenaline), derived from tyrosine, is an important hormone. Penicillamine is a constituent of the penicillin antibiotics. Ornithine, betaine, homocysteine, and homoserine are important metabolic intermediates. Citrulline is the immediate precursor of arginine. 

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. 

Most vitamins function either as a hormone/ chemical messenger (cholecalciferol), structural component in some metabolic process (pantothenic acid), or a coenzyme (phytonadi-one, thiamine, riboflavin, niacin, pyridoxine, biotin, folic acid, cyanocobalamin). At least one vitamin has more than one biochemical role. Vitamin A as an aldehyde (retinal) is a structural component of the visual pigment rhodopsin and, in its acid form (retinoic acid), is a regulator of cell differentiation. The precise biochemical functions of ascorbic acid and a-tocopherol still are not well defined. 

Pantothenic acid is essential for the normal metabolism of fats and carbohydrates. Like many other vitamins, pantothenic acid is abundant in meat, fish, poultry, whole-grain cereals, and legumes. The recommended daily allowance (RDA) of pantothenic acid is 4-7 mg per day. Pantothenic acid deficiency, which is rather rare in the United States except among alcoholics, manifests itself as gastrointestinal, neuromotor, and cardiovascular disorders. Pantothenic acid is converted to its biologically functional form, known as coenzyme A, in the body. Coenzyme A is... 

Pantothenic acid is widely distributed in both plant and animal cells, occurring both in the free and conjugated form. One cannot discuss the relation of adrenocortical function to pantothenic acid without first considering the role of pantothenic acid in intermediary metabolism. 

With the development of knowledge concerning the role of pantothenic acid in intermediary metabolism, the critical importance of this vitamin to adrenocortical function becomes more understandable. When the adrenal cortex is stimulated by stressful situations, its function is to respond rapidly by secreting steroid hormones which initiate and maintain a variety of physiological reactions. Its ability to synthesize these hormones may depend on its capacity to mobilize energy rapidly. Pantothenic acid, as part of coenzyme A, plays a critical role in the oxidative metabolism of both carbohydrate and fatty acids and may also be involved directly in lipid synthesis. Therefore, a deficiency in pantothenic acid can create a situation in which the ability of the adrenocortical cells to secrete steroid hormones is seriously impaired. 

One has only to think of the extraordinarily varied metabolic functions of thiamine, riboflavin, pantothenic acid, pyridoxine, and biotin to realize that it is most unlikely that ascorbic acid could possibly replace every one of these. Moreover, one would have to postulate a quite different mechanism for the large number of other substances, such as sorbitol, sorbose, arabitol, and starch, which spare B vitamins even more readily than ascorbic acid, but which do not have its redox properties. 

Vitamin B5 or pantothenic acid is a water soluble vitamin, which is mainly produced by chemical routes. Pantothenic acid is required for normal skin function as it leads to formation of coenzyme Q and is involved in carbohydrate, protein, and lipid metabolism. Dex-panthenol, an alcoholic analog of pantothenic acid is more stable and has good skin penetration than pantothenic acid. Dexpanthenol is mainly used for topical application on skin and serves as good moisturizer and thus improves the cosmetic appearance of skin. It has mild skin inflammatory activity, but is well tolerated by skin. Pantothenic acid improves wound healing, epidermal regeneration, and reduces scarring also. So, pantothenic acid itself can be used in various skin care formulations. Pantothenic acid is used in hair care formulation as it hydrates the hair and protects the hair fiom chemicals and UV rays. ... 

Vitamins are a well-known group of compounds that are essential for human health. Water-soluble vitamins include folate (vitamin B9) to create DNA. Folate also plays an important role in preventing birth defects during early pregnancy. Thiamine is the first vitamin of the B-complex (vitamin Bl) that researchers discovered. It allows the body to break down alcohol and metabolize carbohydrates and amino acids. Like many other B vitamins, riboflavin (vitamin B2) helps the body to metabolize carbohydrates, proteins, and fat. Niacin (vitamin B3) protects the health of skin cells and keeps the digestive system functioning properly. Pantothenic acid (vitamin B5) and biotin allow the body to obtain energy from macronutrients such as carbohydrates, proteins, and fats. Vitamin B6 (pyridoxine) acts as a coenzyme, which means it helps chemical reactions to take place. It also plays a vital role in the creation of nonessential amino acids. 

The presence of pantothenic acid in this coenzyme and the fact that most, if not all, cellular bound pantothenate is in the form of the coenzyme explain the metabolic function of this vitamin. 

There is considerable basis for linking pyridoxine to amino acid metabolism, and the participation of this vitamin in antibody production may be related to such a function. However, in a recent review, Beaton et al. (1954) suggest that pyridoxine is not essential for protein synthesis or maintenance in the rat and that its effect on amino acid metabolism is of a secondary nature. A role for pantothenic acid in protein synthesis has not yet been demonstrated. A relationship between pantothenic acid and peptide bond formation is suggested by the observation of Chantrenne (1944) that coenzyme A, the coenzyme derivative of pantothenic acid, is... 

Pantothenic acid (sometimes known as vitamin B, and at one time called vitamin B ) has a central role in energy-yielding metabolism as the functional moiety of coenzyme A and in the biosynthesis of fatty acids as the prosthetic group of acyl carrier protein (section 5.6.1). The structures of pantothenic acid and coenzyme A are shown in Figure 11.26. 

Other functions. Pantothenic acid also affects the endocrine glands, and the hormones they produce. Thus, a deficiency of pantothenic acid in rats reduces not only the rate of gain in weight but also the rate of basal metabolism. Also, it has been postulated that the influence which pantothenic acid exerts on the fertility of various animals may be due to some relationship between pantothenic acid and the synthesis of steroid hormones. 

The primary role of pantothenic acid is in acyl group activation for lipid metabolism, involving thiol acylation of CoA or of ACP, both of which contain 4-phosphopantotheine, the active group of which is /3-mercaptoethylamine. CoA is essential for oxidation of fatty acids, pyruvate and a-oxogutarate, for metabolism of sterols, and for acetylation of other molecules, so as to modulate their transport characteristics or functions. Acyl carrier protein, which is synthesized... 

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. 

Some sprays include vitamins such as tocopherols (vitamin E) or panthenol, which is metabolized in the skin to become pantothenic acid, a B vitamin. Since hair does not metabolize ( It s dead, Jim ), these sprays perform the functions of antioxidants (tocopherols). In other words, they add shine and moisture (panthenol) rather than perform their normal vitamin roles. Moisture helps prevent damage during combing. 

NAD and NADP and FMN and FAD, respectively. Pantothenic acid is a component of the acyl group carrier coenzyme A. As its pyrophosphate, thiamin participates in decarboxylation of a-keto acids and folic acid and cobamide coenzymes function in one-carbon metabolism. 

Pantothenic acid Functional part of CoA and acyl carrier protein fatty acid synthesis and metabolism ... 

Pantothenic acid has a central role in acyl group metabolism when acting as the pantetheine functional moiety of coenzyme A or acyl carrier protein (ACP) (Figure 45-18). The pantetheine moiety is formed after combination of pantothenate with cysteine, which provides... 

Rice bran is the richest natural source of B-complex vitamins. Considerable amounts of thiamin (Bl), riboflavin (B2), niacin (B3), pantothenic acid (B5) and pyridoxin (B6) are available in rice bran (Table 17.1). Thiamin (Bl) is central to carbohydrate metabolism and kreb s cycle function. Niacin (B3) also plays a key role in carbohydrate metabolism for the synthesis of GTF (Glucose Tolerance Factor). As a pre-cursor to NAD (nicotinamide adenine dinucleotide-oxidized form), it is an important metabolite concerned with intracellular energy production. It prevents the depletion of NAD in the pancreatic beta cells. It also promotes healthy cholesterol levels not only by decreasing LDL-C but also by improving HDL-C. It is the safest nutritional approach to normalizing cholesterol levels. Pyridoxine (B6) helps to regulate blood glucose levels, prevents peripheral neuropathy in diabetics and improves the immune function. 

The water-soluble vitamins generally function as cofactors for metabolism enzymes such as those involved in the production of energy from carbohydrates and fats. Their members consist of vitamin C and vitamin B complex which include thiamine, riboflavin (vitamin B2), nicotinic acid, pyridoxine, pantothenic acid, folic acid, cobalamin (vitamin B12), inositol, and biotin. A number of recent publications have demonstrated that vitamin carriers can transport various types of water-soluble vitamins, but the carrier-mediated systems seem negligible for the membrane transport of fat-soluble vitamins such as vitamin A, D, E, and K. 

Pantothenic acid and biotin were thus found to be growth factors for yeast. Like riboflavin these molecules are incorporated into larger molecules in order to exert their essential metabolic function. Unlike the other vitamins there has been no evidence of pathological signs in man which can be attributed to dietary deficiencies in biotin or pantothenic acid. 

Vitamins are chemically unrelated organic compounds that cannot be synthesized by humans and, therefore, must must be supplied by the diet. Nine vitamins (folic acid, cobalamin, ascorbic acid, pyridoxine, thiamine, niacin, riboflavin, biotin, and pantothenic acid) are classified as water-soluble, whereas four vitamins (vitamins A, D, K, and E) are termed fat-soluble (Figure 28.1). Vitamins are required to perform specific cellular functions, for example, many of the water-soluble vitamins are precursors of coenzymes for the enzymes of intermediary metabolism. In contrast to the water-soluble vitamins, only one fat soluble vitamin (vitamin K) has a coenzyme function. These vitamins are released, absorbed, and transported with the fat of the diet. They are not readily excreted in the urine, and significant quantities are stored in Die liver and adipose tissue. In fact, consumption of vitamins A and D in exoess of the recommended dietary allowances can lead to accumulation of toxic quantities of these compounds. 

The relationship of carbohydrate metabolism to adrenal function and to pantothenic acid was discussed in Section IV. 

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