Acetyl pantetheine

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. 

Gel filtration of purified 6-MSAS indicates that it is a 750 kDa homotetramer [120]. When treated with 1,3-dibromopropanone (DBP), 6-MSAS behaves similarly to animal FASs and inactivation occurs concomitantly with its cross-linking to a covalent homodimer. By analogy to the well-characterized DBP cross-linked yeast and animal FASs [61,62,79,80], DBP is suggested to cross-link active site sulfhydryl residues of the -ketoacyl synthase cysteine and the AGP pantetheine. This notion is supported by the observation that preincubation with either acetyl or malonyl CoA precludes cross-linking. Thus, the functional significance of the tetrameric assembly of 6-MSAS remains a mystery. 

S-Acetylation. Thiolacetic acid, or an aqueous solution of the sodium salt, has been used for S-acetylation of coenzyme A = and of pantetheine. A Merck group ... 

During the first reaction on fatty acid synthase, acetyl transacylase catalyzes the transfer of the acetyl group from an acetyl-CoA molecule to the SH group of a cysteinyl residue of /J-ketoacyl-ACP synthase. Malonyl-ACP is formed when malonyl transacylase transfers a malonyl group from malonyl-CoA to the SH group of the pantetheine prosthetic group of ACP (reaction 2). Then /J-keto-acyl-ACP synthase catalyzes a condensation reaction (reaction 3) in which ace-toacetyl-ACP is formed (Figure 12.14). 

One of the reasons for its widespread use is based on the fact that CoA - and the CoA-derived phospho-pantetheine tether found on various carrier proteins - acts as the major carrier of metabolites containing carboxylic acid groups short and long carbon chain acids, Krebs cycle metabolites, and amino acids are the most common compounds carried. However, at any given moment most CoA molecules are involved in the transfer of acetyl groups among a variety of both small and macromolecules, and consequently it is from this role that the cofactor derives the name that Lipmann originally bestowed on it Coenzyme A, to indicate its involvement in activation of acetate. ... 

Coenzyme A. CoA. C HjjNjO PjS mol wt 767.55. C 32.86%, H 4.73%, N 12.78%, O 33.35%, P 12.11%, S 4.18%, A co-factor in enzymatic acetyl transfer reactions. The molecule is built up from pantetheine [Lactobacillus bulgaricus factor consisting of pantothenic acid and cyste-amine (thioethylamine 0-mercaptoethylamine decarboxyl -ated cysteine)], adenosine, and phosphoric acid. Iscln from... 

Calcium-D-Pantetheine-S-Sulfonate (PaSSOSCa) [35] and N acetyl glucosamine (NAG) [14] act as inhibitors to glycosylation. Inhibitors to inflammation-induced melanogenic response are M. chamo-milla, topical corticosteroids, glabridin [153], and tranexamic acid. Linoleic and alpha-linolenic acid [4] degrade tyrosinase after melanin has been synthesized. 

Table 1. Reactions of fatty acid synthesis. The enzyme possesses a peripheral SH-group (which belongs to a cysteine residue) and a central SH-group (which belongs to pantetheine). With the exception of acetyl-CoA carboxylase, the catalytic activities listed below (together with acyl carrier protein) may belong to discrete proteins in a multienzyme complex, or they may all be present in a single multifunctional protein (see Table 2).

In order to demonstrate the manifold catalytic activities attributed to the enzyme, which was visualized as a multienzyme complex, we were able to utilize the earlier experience gained, by replacing the complicated coenzyme A residue by iV-acetyl cysteamine or pantetheine. For the problem under discussion, this technique proved to be tremendously useful, so that we were able to demonstrate every single reaction step in our hypothetical sequence independent of preceding or subsequent reactions. The affinity of these model compounds is generally rather low compared with the natural substrates. But this could be circumvented by employing high concentrations of the model substrates. 

Specific for malonate not a saturated acyl-CoA. Malonyl-S-pantetheine is also a substrate. Both enzymes (1 and 2) were characterized by (i) the amount of C-acetate or malonate transferred to ACP or (ii) paper chromatography of acetyl or malonyl hydroxamate. Intermediate is acyl-S-enzyme... 

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