IV VITAMIN BIOSYNTHESIS II5 



mutant that does not utilize desthiobiotin (Wright and Driscoll, 1954). Biotin has 

 been implicated in a number of reversible carboxylation reactions (Lardy and 

 Peansky, 1953; Plant, 195 1). 



7. Myoinositol 



Myoinositol has been shown to be essential for the survival and growth of a numl^er 

 of microorganisms, and the proliferation of human normal and malignant cells 

 in tissue culture (Eagle et al., 1956b). A deficiency of this factor results in alopecia 

 in mice and rats. Myoinositol is also known to exert a lipotrophic effect independ- 

 ent of that of choline. Glucose is a precursor of myoinositol. The biosynthesis of 

 myoinositol from glucose-''*C has been demonstrated in the internal organs of the 

 young rat and in the chick (Daughaday et al., 1955). The capacity of the adult rat 

 for myoinositol synthesis is however, restricted (Halliday and Anderson, 1955). 



8. Niacin, DPN^ and TPN* 



(a) Nicotinic acid synthesis 



Tryptophane and metabolites derived from it are converted to nicotinic acid 

 derivatives in intact animals and in liver slices. Kynurenine is an intermediate in 

 the conversion. This metabolic pathway has been studied by nutritional, isotopic, 

 genetic, adaptive enzyme, and enzyme experiments; thus, the pathway is well 

 documented in animals, bacteria, Neurospora, and insects (Knox and Mehler, 

 1950; Mehler, 1954) (Fig. 54). Some of the evidence may be summarized as 

 follows: i) the enzyme tryptophane peroxidase, which converts the amino acid 

 to formyl kynurenine occurs in the cytoplasm of liver. 2) Formyl kynurenine is 

 hydrolyzed to kynurenine by the enzyme, formylase. Formylase activity has been 

 observed in animal tissues, bacteria, and Neurospora. Formyl kynurenine accu- 

 mulates when tryptophane is oxidized by liver enzyme systems lacking formylase 

 (Mehler and Knox, 1950). j) Thepyridoxal phosphate requiring enzyme, kynure- 

 ninase, has also been demonstrated in bacteria, Neurospora, and in liver (Mehler, 

 1954). Kynureninase can attack 3-hydroxykynurenine as well as kynurenine. 4) 

 After tryptophane is fed to rats, quinolinic acid, N-methylnicotinamide, kynurenic 

 acid and xanthurenic acid, inetabolic products of kynurenine and 3-hydroxyky- 

 nurenine, are found in the urine (Henderson and Hankes, 1956). 5) Liver mito- 

 chondria catalyze the aerobic conversion of L-kynurenine to 3-hydroxyk\'nurenine; 

 TPNH is required for this hydroxylation (DeCastro etal., 1956). 6) 3-hydroxyky- 

 nurenine can replace niacin in certain Neurospora mutants and it accumulates as 

 a product of tryptophane metabolism in cultures of another niacin requiring 

 mutant. A human tubercular patient given tryptophane, excreted 3-hydroxy- 

 anthranilic acid in the urine. Rat liver preparations convert 3-hydroxyanthranilic 

 acid to quinolinic acid and ferrous ions and ascorbate stimulate this conversion 

 (Miyake et al., 1954), with the formation of a quinone intermediate. Only the 

 synthesis of the intermediate is catalyzed by an enzyme; the subsequent formation 

 of quinolinic acid is spontaneous. An enzyme which does attack the intermediate 

 has been concentrated from extracts of liver. This enzyme converts the inter- 



Literature p. 124 



