Phosphopantothenic acid

Various pathways have been proposed for the conversion of pantothenic acid to coen2yme A (68,69). The currentiy accepted pathway iavolves the foUowiag sequence pantothenate to 4-phosphopantothenic acid (33), 4-phosphopantothenyl cysteiae (34), 4-phosphopantetheiae (7),... 

Red blood cells contain pantothenic acid, 4 -phosphopantothenic acid, and pantetheine. These seem to enter by diffusion, and their function is not known unsurprisingly, because they contain no mitochondria, erythrocytes do not contain CoA (Annous and Song, 1995). The permeability of erythrocytes to pantothenate is normally relatively low, but in red cells infected with malaria parasites, the permeability is increased considerably the vitamin is taken up and utilized by the parasites, which require CoA (Saliba et al., 1998). 

CoA, coenzyme A dephospho-CoA, 3 -dephospho-coenzyme A P-pantothenic acid, 4 -phosphopantothenic acid P-pantothenoyl-cysteine, 4 -phosphopantothenoylcysteine P-pantetheine, 4 -phos-phopantethelne ATP, adenosine 5 -triphosphate ADP, adenosine 5 -dlphosphate AMP, 5 -adenyllc acid CTP, cytidine 5 -triphosphate CMP, 5 -cytldylic acid GTP, guanosine 5 -triphosphate GMP, 5 -guanylic acid ITP, inosine 5 -triphosphate UTP, uridine 5 -tri-phosphate PPl, inorganic pyrophosphate. 

Pantothenic acid is one of the three substrates needed to synthesise coenzyme A. It is phosphory-lated to 4 -phosphopantothenic acid by the action of pantothenate kinase (Abiko et al. 1972). The formation of 4 -phosphopantetheine is a two-step process in which 4 -phosphopantofhenic acid and l-cysteine are first converted to 4 -phosphopantothen-... 

Pantothenate kinase was assayed by the above system for "biosynthesis of CoA" (7), except that 1-cysteine was omitted to avoid further metabolism of 4-phosphopantothenic acid. 

Phosphopantothenic acid reacts with cysteine, forming 4 -phosphopant-othenyl cysteine, which is decarboxylated to 4 -phosphopantetheine in a flavin-dependent reaction. In most bacteria, phosphopantetheinyl cysteine synthase and decarboxylase occur as a single bifunctional enzyme, but the human enzymes occur as two separate proteins (Daugherty et al., 2002). 

PanK (EC 2.7.1.33) catalyzes the first and committed step of CoA biosynthesis the ATP-dependent phosphorylation of pantothenic acid 2 to form 4 -phosphopantothenate 8 (Equation (1)). 

Because the bacterial enzymes are much more readily soluble than the mammalian, the steps of fatty acid synthesis have been elucidated in E. coli. The multiple-enzyme complex has been resolved into at least 7 protein components, 6 of which have specific enzyme activities. The other is referred to as the acyl carrier protein. The bacterial carrier protein (mol wt approximately 16,000) is rich in acidic residues and contains a 4 -phosphopantothenic prosthetic group, which, as we shall see, plays a key role in the binding of the acyl group. The prosthetic group is bound to a serine residue of the carrier protein. The carrier protein acts as an acceptor of the acetyl group attached to the SH group of CoA in a reaction catalyzed by an enzyme, acetyl-CoA-ACP transacylase ... 

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