Prosthetic group carrier protein

FIGURE 25.6 Fatty acids are conjugated both to coenzyme A and to acyl carrier protein through the sulfliydryl of phosphopantetheine prosthetic groups. 

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. 

Flavodoxins are a group of flavoproteins which function as electron carriers at low potential in oxidation-reduction systems. The proteins of this group contain one molecule of FMN as their prosthetic group, but, in contrast to ferredoxins, do not contain metals such as iron. 

The prosthetic groups of iron-sulfur proteins fall into several classes (Lov-enberg, 1977 Spiro 1982). Rubredoxins bind single iron atoms with four cys-teinyl sulfur ligands they function as electron carriers in some bacterial systems. Rubredoxins generally have two such centers per molecule in the ferric state each iron center is EPR detectable. 

FIGURE 21-4 Acyl carrier protein (ACP). The prosthetic group is 4 -phosphopantetheine, which is covalently attached to the hydroxyl group of a Ser residue in ACP. Phosphopantetheine contains the B vitamin pantothenic acid, also found in the coenzyme A molecule. Its —SH group is the site of entry of malonyl groups during fatty acid synthesis. 

After malonyl-CoA synthesis, the remaining steps in fatty acid synthesis occur on fatty acid synthase, which exists as a multienzyme complex. In the initial reactions acetyl-CoA and malonyl-CoA are transferred onto the protein complex by acetyl-CoA transacylase and malonyl-CoA transacylase (step 1 and step 2 in fig. 18.12a). The acceptor for the acetyl and malonyl groups is acyl carrier protein (ACP). ACP also carries all of the intermediates during fatty acid biosynthesis. The prosthetic group that binds these intermediates is... 

The second proton transfer mechanism involves protonation of carboxyl or histidyl groups associated with electron carriers in the membrane and release of protons from these sites through proposed channels when the electron carrier is oxidized. This is essentially a proton channel system with movement through the channel gated by the oxidation-reduction state of the prosthetic group on the electron transport protein. The classical example of this is seen in cytochrome c oxidase (Figure 3). 

Pantothenic acid has a central role in energy-yielding metabolism as the functional moiety of coenzyme A (CoA), in the biosynthesis of fatty acids as the prosthetic group of acyl carrier protein, and through its role in CoA in the mitochondrial elongation of fatty acids the biosynthesis of steroids, porphyrins, and acetylcholine and other acyl transfer reactions, including postsynthetic acylation of proteins. Perhaps 4% of all known enzymes utilize CoA derivatives. CoA is also bound by disulfide links to protein cysteine residues in sporulating bacteria, where it may be involved with heat resistance of the spores, and in mitochondrial proteins, where it seems to be involved in the assembly of active cytochrome c oxidase and ATP synthetase complexes. 

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