274 ENZYMES 



cleaves pyruvic acid into carbon dioxide and a two carbon fragment 

 (acetaldehyde in yeast) contains thiamine pyrophosphate (cocarboxy- 

 lase) (Fig. 10-4) as a coenzyme. The degradation of fatty acids to 

 two carbon compounds (Fig. 13^) does not require the presence of thi- 

 amine pyrophosphate. In animals on a low-thiamine, high-fat diet the 

 supply of two carbon fragments from carbohydrate is limited owing to 

 the small quantity of cocarboxylase in the tissues, but this deficiency 

 is compensated by the generation of these metabolic intermediates in 

 adequate amounts from fat. 



A compound of cocarboxylase and lipoic acid, lipothiamide (LTPP), 

 acts as a coenzyme for the oxidative decarboxylation of pyruvic acid 

 and a-ketoglutaric acid by certain bacteria, e.g., E.coli. In an enzyme 

 system obtained from this organism the following series of reactions has 

 been demonstrated: 



pyruvate (a-ketoglutarate) -|- LTPP + DPN^ 



acetyl LTPP (succinyl LTPP) + COo + DPNHa 

 acetyl LTPP (succinyl LTPP) +CoA-^ acetyl Co A (succinyl Co A) + LTPP 



2. Coenzyme A. Lipmann and co-workers discovered that a coenzyme 

 is necessary for the acetylation of sulfanilamide. Subsequent studies 

 demonstrated that the same substance is required for the metabolic forma- 

 tion of acetylcholine from choline and for the condensation of oxalacetic 

 acid with the two carbon fragments from fat or carbohydrate metabolism 

 to produce citric acid (Fig. 13-4). Since in each case acetic acid or an 

 acetyl group seemed to be involved, the coenzyme was named coenzyme 

 A {Co A), a "coenzyme for acetylation." Chemical investigations re- 



^HjJ>0,H, 



9 ?l 9. ^ OH 



■ I I I II II I 



CHCHCH-CHCH,OP-0-PO-CH,C(CH,),CHCONH-CH,CH,CO-NH-CH,CH,SH 



NHr *• 



Fig. 16-5. Structure of coenzyme A suggested by Baddiley and Thain. 

 It is possible that this formula will require some revision as fuller informa- 

 tion becomes available. 



vealed that Co A was a derivative of pantothenic acid, thus providing 

 an insight into the metabolic functions of this B vitamin. The Co A 

 molecule also appears to contain adenine, ribose, ^-thioethylamine, and 

 two or three phosphate radicals. Although the exact chemical formula 

 is not yet known, a suggested structure is given in Fig. 10-5. The sub- 

 stance seems to function by accepting acetyl groups from one metabolite 



