Cellular Metabolism 



75 



net gain of labile phosphate is three per glucose 

 residue for the change of glycogen to pyruvate. 



Pyruvate appears to occupy a key position in the 

 metabolic scheme (cf. Barron, '52), and a number 

 of things can happen to it in addition to rephos- 

 phorylation. With the intervention of the appro- 

 priate DPN enzyme, lactic acid may be formed by 

 the reduction of pyruvate. If this were the end point 

 of sugar breakdown the process would be termed 

 lactic acid fermentation or glycolysis and the bal- 

 ance sheet would show two labile phosphate groups 

 formed per sugar molecule, the DPN coenzyme 



formation of acetate may be involved.* In any 

 event, an oxidative decarboxylation occurs, presum- 

 ably following hydration or phosphorylation. In 

 oxidative decarboxylation is found the third coen- 

 zyme system of general occurrence, cocarboxylase 

 or diphosphothiamine. 



The six-carbon derivative then starts on the cycle 

 pictured in Figure 3, leading to the formation of 

 carbon dioxide (accounting for the two carbon frag- 

 ments added) and the loss of hydrogen through the 

 DPN system (Fig. 5). [The excellent account by 

 Green (in Lardy, '50, Chap. X) may be studied for 



Triose 



P -\- DPN 



Glycerate 



I 



Flavoprot.— rriavoprot. H^ 



2e 



2Fe+++Cyt, 



■2Fef+Cyt. C 

 2e 



2Fe+++Cyt.; 

 Oxidase 



:2Fe+ + Cyt. 

 Oxidase 

 2e 



1/2 0, 



HoO 



AEROBIC 



2H 



DPNH -\- H 



H,e,H 



i 

 Triose — P- 



l-> Pyruvate 



Glycero 



Lactate 



ANAEROBIC 



Fig. 6. Aerobic and anaerobic mechanisms of hydrogen and electron transfer in the oxidation of triose to 

 the glyceric acid level in muscle. (Although not represented in this diagram, oxidation of triosephosphate- 

 glyceraldehyde-3-phosphate involves uptake of one molecule of inorganic phosphate and leads to 1,3-diphos- 

 phoglyceric acid.) (From Ochoa, '47.) 



system having been involved but with no net change 

 in oxidized or reduced forms. In yeast cells and in 

 some other forms, pyruvate is decarboxylated to 

 form acetaldehyde and carbon dioxide, and acetalde- 

 hyde is then reduced with DPNH2 to alcohol. 



Pyruvate may also be reversibly reduced and 

 aminated to form alanine, or condensed with carbon 

 dioxide to form a four-carbon acid (malic acid). Of 

 greatest interest for the general pathway, however, 

 is the entrance of pyruvate into the so-called Krebs- 

 Szent-Gyorgyi cycle (citric acid cycle, etc.). The 

 exact details of the entrance of pyruvate into this 

 cycle are not known, but the condensation of the 

 three-carbon pyruvate with a four-carbon acid re- 

 sults in the formation of a six-carbon citric acid 

 derivative of some sort, plus carbon dioxide. A hypo- 

 thetical seven-carbon "procitric acid" may be 

 formed (cf. Green, in Lardy, '50), or a preliminary 



details of the metabolism of the various components 

 that may enter this cycle. It is here that many fatty 

 acids and other fuels may come into the common 

 scheme.] 



The enzyme system catalyzing this truly cyclic 

 process has been variously named. A useful single 

 term is cyclophorase (cf. Green, in Lardy, '50). 

 As yet, although individual reactions may be 

 studied, the complete system remains associated 

 with the insoluble particles which are collected by 

 centrifugation of homogenates of cellular systems 

 and which are apparently closely allied to the 

 ribose-nucleoprotein components (cf. Green, in 

 Lardy, '50). At least parts of the system are widely 

 distributed (cf. Barron, '43). In its complete form 

 both decarboxylation and oxidation are involved. In 

 large part the system is reversible, a fact of consid- 

 erable interest in view of carbon assimilation by a 



* Since this paper was written, the accumulation 

 of evidence has clearly decided in favor of the second 

 of these alternatives. It now appears that in the pres- 

 ence of DPN and coenzyme A, pyruvate is split to 

 yield reduced DPN, CO2, and acetyl CoA. In the 



presence of a condensing enzyme, the latter sub- 

 stance transfers its acetyl to oxalacetate, thus form- 

 ing citrate. Acetyl CoA can also be generated from 

 acetaldehyde, fatty acids, /3-keto fatty acids, and 

 acetate (cf. Ochoa and Stern, '52). 



