PANTOTHENIC ACID 



By using two cultures of yeast, one rich and one poor in co- 

 enzyme A, G. D. Novelli and F. Lipmann ^^ demonstrated that the 

 coenz3ane was concerned with the primary attack on acetate, since 

 this disappeared from solution twice as rapidly with the high coenzyme 

 yeast as with the low, and when ethanol was used as substrate, acetate 

 accumulated in the solution with the low coenzyme yeast but not 

 with the yeast rich in coenzyme A. 



A method of assaying coenzyme A, based on the observation that 

 when pigeon liver extract undergoes autolysis it loses its ability to 

 acetylate sulphanilamide, was used to determine the distribution of 

 the coenzyme in nature ; reactivation of the extract was proportional 

 to the coenzyme A concentration.-^* It was found to be a general 

 constituent of living organisms ; liver, Clostridium hutylicum and 

 Proteus ^morganii were especially rich sources. Coenzyme A was as 

 active as free pantothenic acid when given intraperitoneally to chicks, 

 but by the oral route it had only 60 % of the activity. ^^ Whereas 

 normal rats acetylated 70 % of the ^-aminobenzoic acid excreted 

 following the injection of a i- or 2-5-mg. dose, pantothenic acid- 

 deficient rats excreted only 50 and 37 % respectively ; the simultaneous 

 injection of I mg. of calcium pantothenate increased the acetylation 

 to normal. ^^ 



Administration of pantothenic acid failed to increase the acetyla- 

 tion of ^-aminobenzoic acid in diabetic rats, although normal values 

 were obtained after injection of insulin, adenosine triphosphate, 

 acetyl phosphate, diacetyl or dicarboxylic acids of the tricarboxylic 

 acid cycle. ^^ It is suggested that insulin may promote the reaction 

 between pyruvic acid and the tricarboxylic acid cycle, a suggestion 

 not inconsistent with the view that pantothenic acid is associated 

 with the conversion of pyruvic acid into acetic acid. 



Preparations of coenzyme A made from pigeon liver extracts 

 acetylated acetic acid (giving acetoacetic acid) and sulphanilamide,^^ 

 whilst pantothenic acid-deficient rats excreted much less sulphanil- 

 amide in the acetylated form than did controls.^ ^ 



The coenzyme A content of rats maintained on a pantothenic acid- 

 deficient diet remained normal for two to three weeks and then fell to 

 a level 35 to 50 % that of normal. Ducklings showed a more rapid 

 depletion, and the injection of pantothenic acid restored the value to 

 normal. 20 Liver slices from pantothenic acid-deficient rats or ducks 

 showed a decreased ability to utilise pyruvic acid. All the panto- 

 thenic acid can be liberated from coenzyme A and made available for 

 microbiological assay by incubation with a mixture of intestinal 

 phosphatase and fresh pigeon liver extract ; assays confirmed the 

 earlier observation that most if not all the pantothenic acid in living 

 cells is bound in the form of coenzyme A.^^ Coenzyme A stimulated 



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