Pantothenate synthetase

Aspartic acid decarboxylase cataly2es the decarboxylation of asparatic acid to yield P-alanine (10), a precursor for the biosynthesis of pantothenic acid (67). FiaaHy, (R)-pantothenic acid is obtaiaed by coupling P-alaniae (10) with (R)-pantoate (22) ia the presence of pantothenate synthetase ... 

Fig. 14 Thioadenosine-derived library used for probing the adenosine-binding pocket of pantothenate synthetase...

Sledz P, Silvestre HL, Hung AW et al (2010) Optimization of the interligand Overhauser effect for fragment linking application to inhibitor discovery against Mycobacterium tuberculosis pantothenate synthetase. J Am Chem Soc 132 45))-)545... 

KPHMT Ketopantoate hydroxymethyltransferase KPR Ketopantoate reductase ADC Aspartate 1-decarboxylase PS Pantothenate synthetase... 

GENSCHEL, U., POWELL, C.A., ABELL, C., SMITH, A.G., The final step of pantothenate biosynthesis in higher plants Cloning and characterization of pantothenate synthetase from Lotus japonicus and Oryza sativum (rice), Biochem. J., 1999,341,669-678. 

CiuDi, A., Blundell, T.L, and Abell, C. (2009). plication of fragment growing and fragment linking to the discovery of inhibitors of Mycobacterium tuberculosis pantothenate synthetase. An mmdte Chemie, International Edition, 48,8452-8456. 

PUutothenie acid is a widely distributed compound in animals and plants, consisting of 2,4-dihydroxy-33-dimethylbutync acid (pantoic acid) linked to alanine by an amide bond Most organisms have the abili to synthesize pantoic acid from valine, and P-alanine from asparate, but humans lack the enzyme, pantothenate synthetase, which catalyses the condensation of p-alanine and pantoic acid to form pantothenic add Only the n(-i-)-form of pantothenic add is biologically active. It is required for the synthesis of Coenzyme A (see). Non-experimental human defi-dency states have not been observed, so pantothenic add is presumably present in suffident quantity in all diets. 

Fig. 187. Biosynthesis of coenzyme A 1 Pantothenate synthetase, pantothenate kinase 2 phosphopantothenoylcysteine synthetase 3 phosphopantothenoylcysteine decarboxylase 4 dephospho-CoA synthetase 5 dephospho-CoA kinase...

Pantothenic acid is synthesized in plants and some microorganisms from pantoic acid and p-alanine. Pantoic acid is formed from 2-oxopantoic acid (4-hydroxy-3,3-dimethyl-2-oxobutyric acid) and 2-oxoisovaleric acid (3-methyl-2-oxobu-tyric acid), a precursor of valine. P-Alanine is formed by decarboxylation of l-aspartic acid. Enzymes involved include pantothenate synthetase (EC 6.3.2.1), oxopantoate reductase (EC 1.1.1.169), oxopantoate hydroxymethyltransferase (EC 4.1.2.12), and aspartate 1-decarboxylase (EC 4.1.1.12). 

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