Pantothenic Coenzyme

Biochemically, the pantothenate coenzymes are integral in the metabolism of carbohydrates, lipids, and nitrogen-containing compounds (185,186). They participate in the TCA or Krebs cycle, as well as fatty acid, phospholipid, sterol (cholesterol), and heme synthesis. The coenzymes mediate the exchange of 2-carbon (acetyl) and other acyl groups. They can serve as... 

Pantothenic acid (pantothenate) Coenzyme A (CoASH) Acyl transfer —... 

Various labeled degradation products of pantothenic acid and coenzyme A are known. Both (l- C)-sodium pantothenate (27) and (R)-(l- C)-panthenol are... 

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, sometimes called vitamin B3, is a vitamin that makes up one part of a complex coenzyme called coenzyme A (CoA) (Figure 18.23). Pantothenic acid is also a constituent of acyl carrier proteins. Coenzyme A consists of 3, 5 -adenosine bisphosphate joined to 4-phosphopantetheine in a phosphoric anhydride linkage. Phosphopantetheine in turn consists of three parts /3-mercaptoethylamine linked to /3-alanine, which makes an amide bond with a branched-chain dihydroxy acid. As was the case for the nicotinamide and flavin coenzymes, the adenine nucleotide moiety of CoA acts as a recognition site, increasing the affinity and specificity of CoA binding to its enzymes. 

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... 

Pantothenic acid is an essential component of coenzyme A (CoA) (Fig. 2) and - as pantetheine - of fatty acid synthase. The HS-group of cysteamine is... 

Panthenol is the alcohol form of pantothenic acid, more familiar as vitamin B5. In a living cell, panthenol is converted to pantothenic acid, which then becomes an important part of the compound coenzyme A, which is important in cellular metabolism. In hair, which contains no living cells, it remains panthenol. 

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 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... 

Figure 45-18. Pantothenic acid and coenzyme A. Shows the site of acyiation by fatty acids.

Pantothenic acid is present in coenzyme A and acyl carrier protein, which act as carriers for acyl groups in metabolic reactions. Pyridoxine, as pyridoxal phosphate, is the coenzyme for several enzymes of amino acid metabolism, including the aminotransferases, and of glycogen phosphorylase. Biotin is the coenzyme for several carboxylase enzymes. 

BaddUey J. Thain, E.M. (1951) The Synthesis of Pantothenic Acid-2 and -4 Phosphates as Possible Degradation Products of Coenzyme A. Journal of the Chemical Society, 246-251. 

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) -... 

Pantothenate in blood and tissues is bound (R9) and released by autolysis or hydrolysis. More vitamin could be released by use of an alkaline phosphatase and an enzyme from avian liver (L6). This method liberates pantothenate from coenzyme A in a variety of foods and tissues (N3, N4). A comparison of hydrolytic methods in blood suggested autolysis to be the most advantageous method (N3) in our hands, treatment with Clarase gave more reliable results as compared with autolysis, acid hydrolysis, treatment with Mylase P, or combination of Clarase and papain, or liver enzyme and alkaline phosphatase. In urine, pantothenic acid is unbound our results show no increase with Clarase treatment. The vitamin has presumably a low threshold. Pantothenic acid shows the same concentration in blood and cerebrospinal fluid. 

ATP and magnesium were required for the activation of acetate. Acetylations were inhibited by mercuric chloride suggesting an SH group was involved in the reaction either on the enzyme or, like lipoic acid, as a cofactor. Experiments from Lipmann s laboratory then demonstrated that a relatively heat-stable coenzyme was needed—a coenzyme for acetylation—coenzyme A (1945). The thiol-dependence appeared to be associated with the coenzyme. There was also a strong correlation between active coenzyme preparations and the presence in them of pantothenic acid—a widely distributed molecule which was a growth factor for some microorganisms and which, by 1942-1943, had been shown to be required for the oxidation of pyruvate. 

It is now well known that pantothenic acid is a part of coenzyme A, a substance of unusual biochemical significance in that it is intimately concerned with the utilization of carbohydrates, and both the utilization and synthesis of fats, sterols, steriod hormones, etc. A partial failure of any of the processes in which it is concerned may not produce a specific lesion, but may nevertheless be a serious detriment to the individual experiencing it. 

Finally, we come to the last of the vitamins that appear on the contents list of my multivitamin pill—pantothenic acid. This water-soluble vitamin serves a single purpose in physiology and biochemistry it is a precursor to a far more complex molecule known as coenzyme A or, simply, CoASH. 

Once the human body has a supply of pantothenic acid, it can add the remaining parts to create the intact molecule. The business part of coenzyme A is a terminal sulfhydryl (—SH) group. It is here that acyl (e.g., the acetyl group, —COCH3) groups are attached in the process of acyl transfer reactions. There are a large number of such reactions in human metabolism and they are concerned with all aspects of... 

Pantothenic acid is a metabolic precursor to coenzyme A, which is involved in a very large number of reactions that occur in all phases of metabolism. 

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. 

Coenzyme A a derivative of pantothenic acid required for many reactions in human metabolism. 

Pancreatic iipase a gut enzyme that initiates the digestion of dietary fats. Pantothenic acid a vitamin that is a precursor for coenzyme A. 

This is a complex molecule, made up of an adenine nucleotide (ADP-3 -phosphate), pantothenic acid (vitamin B5), and cysteamine (2-mercaptoethylamine), but for mechanism purposes can be thought of as a simple thiol, HSCoA. Pre-eminent amongst the biochemical thioesters is the thioester of acetic acid, acetyl-coenzyme A (acetyl-CoA). This compound plays a key role in the biosynthesis and metabolism of fatty acids (see Sections 15.4 and 15.5), as well as being a building block for the biosynthesis of a wide range of natural products, such as phenols and macrolide antibiotics (see Box 10.4). 

Another acid amide bond (-CO-NH-) creates the compound for the next constituent, pantoinate. This compound contains a chiral center and can therefore appear in two enantiomeric forms (see p.8). In natural coenzyme A, only one of the two forms is found, the (R)-pantoinate. Human metabolism is not capable of producing pantoinate itself, and it therefore has to take up a compound of (1-alanine and pantoinate— pantothenate ( pantothenic acid )—in the form of a vitamin in food (see p.366). 

The section of the molecule discussed so far represents a functional unit. In the cell, it is produced from pantothenate. The molecule also occurs in a protein-bound form as 4 -phosphopantetheine in the enzyme fatty acid synthase (see p. 168). In coenzyme A, however, it is bound to 3, 5 -adenosine diphosphate. 

Acyl residues are usually activated by transfer to coenzyme A (2). In coenzyme A (see p. 12), pantetheine is linked to 3 -phos-pho-ADP by a phosphoric acid anhydride bond. Pantetheine consists of three components connected by amide bonds—pantoic acid, alanine, and cysteamine. The latter two components are biogenic amines formed by the decarboxylation of aspartate and cysteine, respectively. The compound formed from pantoic acid and p-alanine (pantothenic acid) has vitamin-like characteristics for humans (see p. 368). Reactions between the thiol group of the cysteamine residue and carboxylic acids give rise to thioesters, such as acetyl CoA. This reaction is strongly endergonic, and it is therefore coupled to exergonic processes. Thioesters represent the activated form of carboxylic adds, because acyl residues of this type have a high chemical potential and are easily transferred to other molecules. This property is often exploited in metabolism. 

Pantothenic acid is an acid amide consisting of p-alanine and 2,4-dihydroxy-3,3 -di-methylbutyrate (pantoic acid). It is a precursor of coenzyme A, which is required for activation of acyl residues in the lipid metabolism (see pp. 12,106). Acyl carrier protein (ACP see p.l68) also contains pantothenic acid as part of its prosthetic group. Due to the widespread availability of pantothenic acid in food (Greek pantothen = from everywhere ), deficiency diseases are rare. 

The synthetic form is the alcohol, panthenol, which can be oxidized in vivo to pantothenic acid. It is included in the list of substances that may be added in foods and in food supplements [403], Pantothenic acid is part of the coenzyme A (CoA) molecule therefore it is involved in acylation reactions, such as in fatty acid and carbohydrate metabolism. 

Pantothenic acid occurs in foods both in the free form and bonded to coenzyme (CoA) or acyl carrier protein (ACP) therefore hydrolysis is needed to extract it totally. Since it is degraded by acid and alkaline hydrolysis, only an enzymatic digestion can be applied. Enzyme hydrolysis with papain, diastase, clarase, takadiastase, intestinal phosphatase, pigeon liver pantetheinase, or combination of them has been used. 

Coenzyme A Loose Pantothenic acid (B5) Esterified to organic acids in many steps of fatty acid and carbohydrate metabolism... 

Pantothenic acid (vitamin B5) is both present in many nutrientcients and it is also produced by intestinal bacteria. Deficiency is therefore thought to be unlikely. Its active form, 4-phosphopantetheine, is an element of both coenzyme-A and acyl-carrier protein and thus participates in fatty acid synthesis and in the posttranslational modification of proteins. Acetylcoenzyme-A is important for the synthesis of the neurotransmitter acetylcholine. 

Pantothenic acid Coenzyme A Transfer of acetyl groups... 

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