Oxidative Pathways of Carbohydrate Metabolism 161 



Such mechanisms can couple TPN and DPN-specific 

 enzymes, although they have not as yet been much studied 

 from a functional aspect. In liver, the direct reoxidation of 

 TPNH is very slow in comparison with that of DPNH, and 

 in all tissues studied TPNH greatly predominates over TPN"'" 

 (see below). 



One of the most important functions of TPNH appears to 

 be in reversal of oxidative decarboxylations. Fig. 4 shows the 

 "by-pass" of the energetically difficult phosphorylation of 

 pyruvate to PEP, the importance of which in resynthesis of 

 carbohydrate from lactate or pyruvate has been emphasized 

 by Krebs and Kornberg (1957). This reaction (AC about 

 + 6) is believed to be circumvented in liver as shown in 

 Fig. 4 via reductive carboxylation of pyruvate to malate by 

 the TPNH-linked "malic" enzyme, malate oxidation by 

 DPN+ with malic dehydrogenase to give OAA, and phos- 

 phorylative decarboxylation of the latter to give PEP by the 

 reaction studied by Utter and Karahashi (1954): 



OAA + ITP ^ PEP + CO2 + IDP 



Here, the strongly endergonic reaction with DPN+ (Fig. 4) 

 can be coupled with very efficient reoxidation of the DPNH 

 formed, thus driving the reaction successfully towards OAA. 

 For this "by-pass" to progress, a continuous supply of 

 TPNH has to be available. Fig. 4 illustrates how the HMP 

 oxidative pathway could be successfully coupled with the 

 " malic " enzyme stage, and the pentose phosphate formed from 

 this oxidation of G6P could be resynthesized to hexose by the 

 TK-TA sequence already described: 



(1) 6(G6P2- + 2TPN+ + H2O -> Pentose-P2- + CO2 



-f 2 TPNH -f 2H+) 



(2) 6 pentose-P2- + HgO -> 5 G6P2- + HPO42- 



Sum: G6P2- + 12 TPN+ + THgO -> 6CO2 + 12 TPNH 

 + 12H+ + HPO42- 



CELL METAB. — 6 



