634 F. Dickens 



acid or of glutamate, which utilize TPNH, should also produce a similar 

 shift of metabolic pathway. Several examples of both types of control are 

 already known. 



Thus Hers (1957) showed that addition of substrates of the TPNH-linked 

 aldose reductase present in liver specifically increased the hberation of ^^COg 

 from [1-^^C] glucose in liver slices. By addition of ammonium salts to 

 yeast cells respiring in presence of glucose, Holzer and Witt (1958) produced 

 not only an increased fermentation, but also accompanying this, a marked 

 increase in the oxidative utihzation of glucose 6-phosphate simultaneously 

 with a sharp (30 sec) four-fold increase in the level of oxidized TPN. It was 

 concluded that the very active TPN-specific glutamic dehydrogenase in 

 yeast utilized TPNH and ketoglutarate, in presence of the ammonium salt, 

 to give glutamate and oxidized TPN, thus making the latter available for 

 oxidation of glucose 6-phosphate via the HMP-shunt. 



Wenner, Hackney and Moliterno (1958) showed that addition of methylene 

 blue or a number of other artificial electron acceptors to Ehrlich ascites cells 

 which were respiring in presence of labelled glucose had a similar effect, and 

 increased the oxidation of C-1 of glucose by 6-30 x , with only a slight effect 

 on oxidation at C-6 of glucose (cf. Cahill, Hastings, Ashmore and Zottu 

 (1958) for liver slices). More recently, McLean (1959a, b) has studied in our 

 laboratory the effect of phenazine methosulphate, which is known to be a 

 particularly effective substitute-carrier for enzymes which are normally 

 flavin-linked, and also of insulin, on the oxidative metabolism of slices of 

 rat mammary gland. The results are summarized in Table 4. 



Table 4. Mammary gland slices (rat): action of insulin and 

 phenazine methosulphate on percentage oxidation of [1-1*c] 



GLUCOSE TO ^''COo 



(McLean, 1959a, b). 500 mg tissue; 4-5 ml Krebs-bicarbonate; 

 20 mg glucose (0-2 //c); O^ + 5 % COo; 38°C. 



20 Days pregnancy JO Days lactati 



Control 2% 12% 



-t- Insulin (1 l.U.) 3"^ 28% 



+ Phenazine (lO"" m) 13% 36% 



In the pregnant, non-lactating rat insulin does not increase the rate of 

 formation of fatty acid, and has no significant effect on the conversion of 

 [1-^*C] glucose to ^^COa. In the lactating gland, however, insulin greatly 

 increases both fatty acid synthesis and [1-^'^C] liberation from labelled 

 glucose (cf. Abraham, Cady and Chaikoff, 1957). 



The effect of phenazine methosulphate (10~^m) on slices of the lactating 

 gland is similar to, but even more striking than, that of insulin (Table 4). 



