Pantothenic acid coenzymes derived from

Description. Also known as vitamin Bj, pantothenic acid is essential to all forms of life. Pantothenic acid is found throughout living cells in the form of coenzyme A (CoA), a vital coenzyme in numerous chemical reactions. The term pantothenic acid is derived from the Greek word pantos, meaning everywhere. 

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. 

Pantothenic acid is found in extracts from nearly all plants, bacteria, and animals, and the name derives from the Greek pantos, meaning everywhere. It is required in the diet of all vertebrates, but some microorganisms produce it in the rumens of animals such as cattle and sheep. This vitamin is widely distributed in foods common to the human diet, and deficiencies are only observed in cases of severe malnutrition. The eminent German-born biochemist Fritz Lipmann was the first to show that a coenzyme was required to facilitate biological acetylation reactions. (The A in... 

The hydrogenation of ketones with O or N functions in the a- or / -position is accomplished by several rhodium compounds [46 a, b, e, g, i, j, m, 56], Many of these examples have been applied in the synthesis of biologically active chiral products [59]. One of the first examples was the asymmetric synthesis of pantothenic acid, a member of the B complex vitamins and an important constituent of coenzyme A. Ojima et al. first described this synthesis in 1978, the most significant step being the enantioselective reduction of a cyclic a-keto ester, dihydro-4,4-dimethyl-2,3-furandione, to D-(-)-pantoyl lactone. A rhodium complex derived from [RhCl(COD)]2 and the chiral pyrrolidino diphosphine, (2S,4S)-N-tert-butoxy-carbonyl-4-diphenylphosphino-2-diphenylphosphinomethyl-pyrrolidine ((S, S) -... 

Note that this overall reaction requires three coenzymes that we encountered as metabolites of vitamins in chapter 15 NAD+, derived from lucotiiuc acid or nicotinamide FAD, derived from riboflavin and coenzyme A(CoASH), derived from pantothenic acid. In the overall process, acetyl-SCoA is oxidized to two molecules of carbon dioxide with the release of CoASH. Both NAD+ and FAD are reduced to, respectively, NADH and FADH2. Note that one molecule of guanosine triphosphate, GTP, functionally equivalent to ATP, is generated in the process. 

Some enzymes associate with a nonprotein cofactor that is needed for enzymic activity. Commonly encountered cofactors include metal ions such as Zn2+ or Fe2+, and organic molecules, known as coenzymes, that are often derivatives of vitamins. For example, the coenzyme NAD+contains niacin, FAD contains riboflavin, and coenzyme A contains pantothenic acid. (See pp. 371-379 for the role of vitamins as precursors of coenzymes.) Holoenzyme refers to the enzyme with its cofactor. Apoenzyme refers to the protein portion of the holoenzyme. In the absence of the appropriate cofactor, the apoenzyme typically does not show biologic activity. A prosthetic group is a tightly bound coenzyme that does not dissociate from the enzyme (for example, the biotin bound to carboxylases, see p. 379). 

Coenzyme A (abbreviated CoA or CoASH, 6) was discovered by Lipmann in the 1940s, and its structure was first reported in 1953 (2, 3). The structure of CoA consists of 3 -phosphoadenosine and pantetheine, linked by a pyrophosphate group (Fig. 1). The pantetheine moiety is derived from pantothenic acid 1, also known as vitamin B5. CoA and its... 

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). 

Other cofactors involved in deriving energy from food include coenzyme A (derived from the vitamin pantothenate), thiamine pyrophosphate, and Upoic acid. 

Many other reactions in nature use enamines, mostly those formed from lysine. However, a more common enol equivalent is based on thiol esters derived from coenzyme A. Coenzyme A is an adenine nucleotide at one end, linked by a S -pyrophosphate to pantothenic acid, a compound that looks rather like a tripeptide, and then to an amino thiol. Here is the structure broken down into its parts. 

Coenzyme A is derived from the B vitamin pantothenic acid (B5) (see b Figure 12.17). It also contains two other components, a phosphate derivative of ADP and b-mercapto-ethylamine. A key feature in the structure of coenzyme A is the presence of the sulfhydryl group (—SH), which is the reactive portion of the molecule. For this reason, coenzyme A is often abbreviated as CoA—SH. 

Coenzyme A is derived from four subunits. On the left is a two-carbon unit derived from 2-mercaptoethanamine. This unit is in turn joined by an amide bond to the carboxyl group of 3-aminopropanoic acid (/3-alanine). The amino group of /S-alanine is joined by an amide bond to the carboxyl group of pantothenic acid, a vitamin of the B complex. Finally, the —OH group of pantothenic acid is joined by a phosphoric ester bond to the terminal phosphate group of ADP ... 

The complete structure of CoA is now established. The coenzyme is a pantothenic acid derivative in which the vitamin is doubly bound and is liberated by the combined action of two enzymes, an intestinal phosphatase and an unidentified peptidase from avian liver. The latter enzyme has recently been found in fresh extracts of hog kidney... 

Many, although not all, coenzymes are derived from vitamins—substances that an organism requires for growth but is unable to synthesize and must receive in its diet. Coenzyme A from pantothenate (vitamin B3), NAD" from niacin, FAD from riboflavin (vitamin B2), tetrahydrofolate from folic acid, pyridoxal phosphate from pyridoxine (vitamin Be), and thiamin diphosphate from thiamin (vitamin Bi) are examples (Table 19.3). We ll discuss the chemistry and mechanisms of coenzyme reactions at appropriate points later in the text. 

Animals do not synthesize pantothenic acid. However, they, like yeasts and bacteria, convert the exogenous vitamin derived from the diet to coenzyme A (CoA) and acyl-carrier protein (ACP), the two metabolically active forms. The reaction pathway is shown in Eigirre 6. 

Vitamins are coenzymes or coenzyme precursors. Lactic acid bacteria are incapable of synthesizing B-group vitamins, in particular nicotinic acid, thiamin, biotin and pantothenic acid. A glyco-syled derivative of pantothenic acid was identified in grape juice it had been initially purified from tomato juice (Tomato Juice Factor Amachi, 1975). 

FIGURE 18.8 Coenzyme A is derived from a phosphorylated adenosine diphosphate (ADP) and pantothenic acid bonded by an amide bond to aminoethanethiol, which contains the — SH reactive part of the molecule. 

Several p-amino acids occur naturally as free metabolites in metabolic pathways or as key intermediates in biosynthetic products. p-Alanine is the simplest p-amino acid that appears in pantothenic acid, a precursor of the coenzyme A. Further examples are (2R,3S)-N-benzoyl-3-phenylisoserine derived from (R)-p-phenylalanine, a compound in the antitumor agent paclitaxel from Taxus brevifolia [89], or as building blocks for p-lactam antibiotics [90] and in jasplakinolide, an antifungal compound [91] (Scheme 29.12). 

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