IV VITAMIN BIOSYNTHESIS II7 



phosphorylase 



a) Nicotinamide + ribose-i -phosphate ' r nicotinamide riboside -|- Pi 



ATP 



b) Nicotinamide riboside — -^ NMN + ADP 



In the presence of ATP, nicotinamide mononucleotide was also formed (reaction 

 b). Liver and yeast enzymes catalyze the formation of DPN^ from NMN and of 

 TPN" from DPN" (Kornberg, 1950a, b). 



c) NMN + ATP ^ — . DPN^ + PP 



d) DPN^ + ATP —^ TPN^ + ADP 



The reduced form of DPN^ may substitute for DPN* in reaction c) and d). The 

 third phosphate of TPN* is esterified at the 2'-position of the adenosine moiety 

 of the TPN^ molecule (Heppel et al., i955)- 



9. Coenzyme A synthesis 

 [a) Pantoate 



In Bacterium linens, 456, pantothenic acid is required for growth. PABA can 

 however replace pantothenic acid. The growth of PABA requiring bacteria is 

 inhibited competitively by sulfanilamide or salicylate. Since pantoate and keto- 

 pantoate as well as pantothenate reverse the sulfanilamide inhibition non-competi- 

 tively, it seems possible that ketopantoate and pantoate are pantothenate pre- 

 cursors in this organism. This concept is supported by the fact that ketopantoate and 

 pantoate are equivalent to pantothenate as growth factors in the absence of PABA. 



CH^CH— CH — COOH CH, TH 



I I ^ ^^CH— C-COOH PABA, | || 



CH3 NHj CH3 \\^ "HCHO" HO-CH2-C— C— COOH 



CH3 

 Valine d-Ketoisovalerate Ketopantoate 



CH3 

 I 

 HO— CHo— C — CHOH— COOH 

 I 



CH3 

 Pantoate 

 Fig. 55. Pantoate synthesis from valine. 



With limiting concentrations of PABA, a-ketoisovalerate, the keto-analog of 

 valine, enhances the growth of Bacterium linens (Purko et al., 1954). a-ketoiso- 

 valerate is also converted to pantoate in E. coli. Presumably, the PABA is required 

 for the hydroxymethylation of a-ketoisovalerate (Fig. 55). Extracts of acetone 

 dried E. coli cells are active in synthesizing pantothenate from pantoate and 

 [3-alanine (Maas and Novelli, 1953). 



P-Alanine ^ pantoate + ATP — > pantothenate + PP + AMP 



Lileralure p. 124 



