Pantothenic acid cleavage

Pantothenic acid is relatively labile (185,186). In the dry form, it is hygroscopic and unstable in solution its stability is strongly pH dependent, being greatest at pH 4-5. It is subject to hydrolytic cleavage to pantoic acid and /3-alaninc in more acidic or alkaline solutions. Pantothenic acid is very soluble in water, alcohols, and dioxane, less soluble in diethyl ether and acetone, and insoluble in benzene and chloroform. 

The biologically active R- or 5 -pantothenic acid can be obtained upon hydrolysis of coenzyme A with a combiaation of two enzymes, alkaline phosphatase and pantotheiaase (13) (Fig. 1). The phosphatase catalyzes the selective cleavage of the phosphate bond ia coenzyme A to afford adenosin-3 5 -diphosphate (6) and 4-phosphopantetheiae (7). The latter substance is dephosphorylated enzymatically to yield pantetheiae (8), which is rapidly converted by pantotheiaase to pantothenic acid (1). Table 1 Hsts some physical properties of pantothenic acid and its derivatives. 

Significant HMBPA accumulation indicates a metabolic bottleneck at the PanB-catalyzed hydroxymethylation step. Engineering the supply chain for methylene tetrahydrofolate, the cosubstrate of the PanB reaction, by overexpression of SerA and GlyA or of the enzymes of the glycine cleavage cycle drastically reduced HMBPA accumulation in favor of further increased (7 )-pantothenic acid production [177]. This result indicates that insufficient availability of the PanB cosubstrate is a major cause of unwanted side-product formation. 

A substantial advance in the more definitive determination of structure came in 1935 when /3-aIanine, under certain testing conditions, was found to be a powerful yeast growth substancei and later to be produced from pantothenic acid concentrates by cleavage . 

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