Phosphopantetheine, coenzyme structure

Phosphine(s), chirality of, 314 Phosphite, DNA synthesis and, 1115 oxidation of, 1116 Phospholipid, 1066-1067 classification of, 1066 Phosphopantetheine, coenzyme A from. 817 structure of, 1127 Phosphoramidite, DNA synthesis and, 1115 Phosphoranc, 720 Phosphoric acid, pKa of, 51 Phosphoric acid anhydride, 1127 Phosphorus, hybridization of, 20 Phosphorus oxychloride, alcohol dehydration with. 620-622 Phosphorus tribromide, reaction with alcohols. 344. 618 Photochemical reaction, 1181 Photolithography, 505-506 resists for, 505-506 Photon, 419 energy- of. 420 Photosynthesis, 973-974 Phthalic acid, structure of, 753 Phthalimide, Gabriel amine synthesis and, 929... 

Phosphopantetheine coenzymes are the biochemically active forms of the vitamin pantothenic acid. In figure 10.11, 4 -phosphopantetheine is shown as covalently linked to an adenylyl group in coenzyme A or it can also be linked to a protein such as a serine hydroxyl group in acyl carrier protein (ACP). It is also found bonded to proteins that catalyze the activation and polymerization of amino acids to polypeptide antibiotics. Coenzyme A was discovered, purified, and structurally characterized by Fritz Lipmann and colleagues in work for which Lipmann was awarded the Nobel Prize in 1953. 

The success, albeit limited, of incorporation studies of polyketide assembly intermediates has resulted from feeding these in the form of their NAC thioesters which structurally mimic the thiol end of the phosphopantetheine moiety found in coenzyme A and the acyl carrier protein component of the PKS. This will be discussed further below, but it has also been shown that there are advantages to feeding starter units in the form of their NAC thioesters. 

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

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

Figure 20.1 Structure of pantothenic acid and bound form coenzyme A (CoA), phosphopantetheine and pantetheine.

If the mammalian synthetase binding site proves to be acyl carrier protein (AGP), instead of coenzyme A, ihis raises the possibility that herein is another regulatory device. The enzymes of E. coli catalyze fatty acid synthesis many times faster with thioesters of AGP than coenzyme A (Alberts et al., 1964). Since both AGP and GoA have the identical prosthetic group (4 -phosphopantetheine), the specificity must be conferred by some part of the protein structure. Therefore, the rate of synthetase activity could be controlled by availability of AGP. Majerus and Vagelos (1967) have made the suggestion that since AGP hydrolase has such a marked substrate specificity for intact AGP, it might control the rate of fatty acid synthesis by adjusting the amount of AGP available. They cautiously added that direct evidence for such a role is not presently available. ... 

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