Phosphopantetheine groups

The 4-phosphopantetheine group of CoA is also utilized (for essentially the same purposes) in acyl carrier proteins (ACPs) involved in fatty acid biosynthesis (see Chapter 25). In acyl carrier proteins, the 4-phosphopantetheine is covalently linked to a serine hydroxyl group. Pantothenic acid is an essential factor for the metabolism of fat, protein, and carbohydrates in the tricarboxylic acid cycle and other pathways. In view of its universal importance in metabolism, it is surprising that pantothenic acid deficiencies are not a more serious problem in humans, but this vitamin is abundant in almost all foods, so that deficiencies are rarely observed. 

The soluble enzyme system responsible for its synthesis contains a large 280-kDa protein that not only activates the amino acids as aminoacyl adenylates and transfers them to thiol groups of 4 -phosphopantetheine groups covalently attached to the enzyme but also serves as a template for joining the amino acids in proper sequence.211-214 Four amino acids—proline, valine, ornithine (Om), and leucine—are all bound. 

The condensation reactions occur in two steps first the growing fatty acyl chain is transferred from the phosphopantetheine group of an AGP onto a cysteine of the KS. Subsequently, the KS binds and decarboxylates a malonyl-AGP, thereby generating a resonance-delocalized carbanion. The formation and stability of this nucleophilic species could be promoted by electrostatic or... 

The cofactor of fatty acid synthase is bound to the enzyme at a point near a specific residue of cysteine. This cysteine residue is important in the catalytic mechanism. T he sulfhydryl group of this cysteine is used for temporarily holding the fatty acid moiety each time a new molecule of maIonic acid is transferred to the 4-phosphopantetheine group. One might refer to the diagram of the enzyme in Chapter 5, where the sulfhydryl groups of the cysteine residue and of 4-phosphopantetheine are shown. 

Phosphopantetheine group of CoA FIGURE 5.16 The phosphopantetheine group in acyl-carrier protein (ACP) and in CoA. 

The assembly of rat liver FAS involves three stages synthesis of the multifunctional polypeptide chains, formation of the dimer, and attachment of a 4 -phosphopantetheine group by an enzyme-catalyzed reaction. This assembly process is influenced by changes in developmental, hormonal, and nutritional states. The FAS complex provides considerable catalytic efficiency, since free intermediates do not accumulate and the individual activities are present in equal amounts. 

The optional reductive domains in each module needed for ketone group modification (DH, ER and KR) form loops that protrude out sideways from the central core, while maintaining the active sites of all reductive domains within range of the phosphopantetheine group on the adjacent ACP in the same chain. There is therefore no contact between reductive domains of complementary... 

The answer is c. (Murray, pp 627-661. Scriver, pp 3897-3964. Sack, pp 121—138. Wilson, pp 287-320.1 The almost universal carrier of acyl groups is coenzyme A (CoA). However, acyl carrier protein (ACP) also functions as a carrier ol acyl groups. In fatty acid synthesis, ACP carries the acyl intermediates. The reactive prosthetic group of both ACP and CoA is a phosphopantetheine sulfhiydryl. In ACP, the phosphopantetheine group is attached to the 77-residue polypeptide chain via a serine hydroxyl. In CoA, the phosphopantetheine is linked to the 5 -phosphate of adenosine that is phosphorylated in its 3 -hydroxyl. 

Comparison of the Phosphopantetheine Group in Acyl Carrier Protein (ACP) and in Coenzyme A (CoASH). 

The structure of the phosphopantetheine group, the reactive group common to coenzyme A and acyl carrier protein, is highlighted in yellow. 

Acyl group carriers. The activated intermediates of fatty acid biosynthesis are bound to a carrier molecule called the acyl carrier protein (ACP) (Figure 23.12). In p-oxidation the acyl group carrier was coenzyme A. However, there are important similarities between these two carriers. Both contain the phosphopantetheine group, which is made from the vitamin pantothenic acid. In both cases the fatty acyl group is bound by a thioester bond to the phosphopantetheine group. 

What molecules involved in fatty acid degradation and fatty acid biosynthesis contain the phosphopantetheine group ... 

The phosphopantetheine group allows formation of a high-energy thioester bond with a fatty acid. It is derived from the vitamin pantothenic acid. 

FIGURE 21.16 Structural similarities between coenzyme A and the phosphopantetheine group of ACP. 

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