138 THE BIOCHEMISTRY OF B VITAMINS 



Because of this mobile function these two coenzymes have been found 

 to occur in quantities which on an equivalent basis are considerably in 

 excess of the amounts of apoenzymes. Since the oxidized and reduced 

 forms of the coenzymes are kept in equilibrium by these apoenzymes, 

 the ratio of reduced and oxidized molecules will be determined by the 

 redox potential of the cellular environment. It is not surprising, there- 

 fore, that of the total diphosphopyridine nucleotide present in a number 

 of animal tissues, a fairly uniform percentage (35-45 per cent) is in the 

 reduced state. 42 In certain malignant tissues the ratio of reduced form to 

 oxidized form is increased, 43 a change which presumably results from 

 the lowered redox potential maintained by such cells. 



Biosynthesis. The synthesis of the coenzymes from their component 

 units (those formed upon hydrolysis) can apparently be carried out by 

 most organisms. The only known instances in which this total synthesis 

 cannot be accomplished are encountered in the two strains of influenza 

 bacteria previously mentioned (p. 136) . In higher organisms practically 

 all the intracellular nicotinic acid is in the form of its coenzymes, but 

 the extracellular fluids (such as plasma, milk, and urine) contain little, 

 if any, coenzyme. The enzymatic synthesis of both coenzymes is known 

 to occur in vitro in most intact cells, and an enzymatic synthesis of 

 triphosphopyridine nucleotide from nicotinamide, ribose, and adenosine 

 triphosphate has been reported in which only a cell-free extract was 

 used. 44 



Investigations of the specificity of the pyridine component used for 

 the biosynthesis of the coenzyme have disclosed several interesting varia- 

 tions among different types of cells in regard to the utilization of nico- 

 tinic acid and nicotinamide. It appears that the route of synthesis may 

 differ in different types of cells, and that nicotinamide sometimes cannot 

 be directly used for the biosynthesis of the coenzymes. 45 



The synthesis of the triphospho nucleotide from the diphospho com- 

 pound can be accomplished enzymatically. 46 Chemically the conversion 

 can be made by use of phosphorus oxychloride. 30 The phosphorylated 

 substances formed by the enzymatic and chemical syntheses are assumed 

 to be identical with the naturally occurring compound, but chemical 

 proof of their identity has not been established. 



When the organization of cells is disrupted the coenzymes of nicotinic 

 acid are rapidly inactivated by enzymatic hydrolyses. The coenzymes 

 are vulnerable to attack by hydrolytic enzymes at a number of points. 

 In animal tissue, most of the enzymes responsible for the inactivation are 

 believed to hydrolytically cleave the nicotinamide-ribose bond, liberating 

 free nicotinamide. 47 



