160 F. Dickens, G. E. Clock and P. McLean 



and Vignais and Vignais (1957) with mitochondria from liver 

 kidney and brain, obtained only very low P/0 values of about 

 unity or less for TPNH oxidations. While, therefore, it is not 

 justifiable on present evidence to regard the HMP oxidative 

 pathway as an energy source, there are a number of important 

 biological synthetic systems requiring a supply of TPNH (cf. 

 Horecker and Hiatt, 1958). These include carboxylations and 

 aminations of keto acids, fatty acid and steroid synthesis, and 

 reduction at a physiological pH of dihydrofolic acid to 

 tetrahydrofolic acid, an important stage in one-carbon transfer 

 (Peters and Greenberg, 1958); as well as the reduction of 

 glutathione and various hydroxylations and microsomal 

 detoxication mechanisms (Brodie et al., 1955). 



Reoxidation of TPNH can occur {a) by the specific TPNH- 

 cytochrome c reductase, a flavoprotein system occurring in 

 mitochondria together with {h) pyridine nucleotide trans- 

 hydrogenase (Vignais and Vignais, 1957), the latter being 

 weak in liver and brain mitochondria (cf. Navazio, Ernster and 

 Ernster, 1957). (c) Glutathione reductase, {d) Two consecu- 

 tive dehydrogenase reactions each involving one coenzyme 

 e.g. (Holzer and Schneider, 1958): 



(i) TPNH -f H+ + a-ketoglutarate + NH4+ ^ glutamate 

 + TPN+ + H2O 



(ii) Glutamate + DPN+ + HgO :^ a-ketoglutarate + 

 DPNH + H+ + NH4+ 



Sum: TPNH + DPN+ — DPNH + TPN+. 



{e) Another variant is lactic dehydrogenase, which can 

 react with either coenzyme (Navazio, Ernster and Ernster, 

 1957; Holzer and Schneider, 1958). (/) An ingenious coen- 

 zyme-hke role of steroid hormones acting together with 

 placental 17-p-hydroxysteroid dehydrogenase (Talalay and 

 Williams-Ashman, 1958) is as follows: 



DPN+ ->.^Oestradiol^^TPN+ 

 DPNH^>^Oestrone -^^TPNH 



