Pantetheine

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... 

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... 

BaddUey J. Thain, E.M. (1952) Coenzyme A. Part V. A New and Convenient Synthesis of Pantetheine (Lactobacillus hulgaricus Vactor). Journal of the Chemical Society, 800-803. 

Keefe et al. (1995) from Stanley Miller s laboratory reported a possible prebiotic synthesis of pantetheine, the part of the CoA molecule without its ADP moiety. They were able to synthesize the CoA precursor from P-alanine, pantoyllactone and cysteamine. This condensation requires concentration of the reaction mixture the warm lagoon theory is required here in order to achieve prebiotic conditions ... 

There s a lot of shuffling of acyl groups between the pantetheine thiol and the thiol of a cysteine residue of the enzyme. They re shown in the correct position for all the reactions, so you have to do an acyl transfer at the end of each cycle to put the growing acyl chain back on the cysteine residues. The elongation step takes place with the growing acyl chain on cysteine and the malonyl-CoA on the pantetheine. At the end of the condensation reaction, the elongated chain is on the pantetheine. 

Each reaction of p oxidation is catalyzed by a different enzyme. Chemically, they re pretty much the same as the reverse of the individual reaction of fatty acid synthesis, with two exceptions (1) p oxidation uses FAD for the formation of the double bond at the C-2 position, and (2) the reactions occur with the fatty acid attached to CoA rather than to the pantetheine of a multienzyme complex. 

Several amino acids are broken down by de-carbo qflation. This reaction gives rise to what are known as biogenic amines, which have various functions. Some of them are components of biomolecules, such as ethanolamine in phospholipids (see p. 50). Cysteamine and T-alanine are components of coenzyme A (see p.l2) and of pantetheine (see pp. 108, 168). Other amines function as signaling substances. An important neurotransmitter derived from glutamate is y-aminobutyrate (GABA, see p.356). The transmitter dopamine is also a precursor for the catecholamines epinephrine and norepinephrine (see p.352). The biogenic amine serotonin, a substance that has many effects, is synthesized from tryptophan via the intermediate 5-hydroxytryptophan. 

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. 

DIETHYL PYROCARBONATE DEPHOSPHO-CoA KINASE Dephospho-CoA pyrophosphorylase, PANTETHEINE-RHOSRHATE ADENYLYL-TRANSFERASE DEPOLARIZATION ACTION ROTENTIAL HYPERROLARIZATION DEPOLYMERIZATION PROCESSIVITY... 

In E. coli and some plants, the seven active sites for fatty acid synthesis (six enzymes and ACP) reside in seven separate polypeptides (Fig. 21-7, top). In these complexes, each enzyme is positioned with its active site near that of the preceding and succeeding enzymes of the sequence. The flexible pantetheine arm of ACP can reach all the active sites, and it carries the growing fatty acyl chain from one site to the next intermediates are not released from the enzyme complex until it has formed the finished product. As we have seen in earlier chapters, this channeling of intermediates from one active site to the next increases the efficiency of the overall process. 

Low-molecular-mass thiols such as coenzyme A and protein-bound thiol cofactors such as phospho-pantetheine are present in all cells. Their SH groups can also be oxidized to disulfides and it is of interest that in resting bacterial spores these compounds exist largely as disulfides or mixed disulfides. Upon germination of the spores special enzymes reduce the disulfides.136 Some proteins involved in control of protein synthesis contain SH groups that add covalently to C-6 atoms of a uracil ring in specific mRNA molecules. Control of their state of reduction may also be important.137... 

An additional series of reactions,350 which are shown in Eq. 24-38, leads to pantoic acid, pantetheine, coenzyme A, and related cofactors.350a i The initial reactions of the sequence do not occur in the animal body, explaining our need for pantothenic acid as a vitamin. 

It has been shown that the reaction center of multifunctional fatty acid synthases of yeast and animal cells comprises two SH-groups Cys-SH of the condensation enzyme, and pantetheine-SH attached to ACP. The... 

One system in which pantetheine almost certainly performs such a carrier role is the fatty acid synthase from E. coli, in which 4 -phosphopantetheine is a component of the acyl carrier protein (see chapter 18). 

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