CELLULAR METABOLISM II7 



means that the Fe++ porphyrin forms the more stable compound; if the 

 Fe"^"^"*" form associates more strongly than the Fe++ form the trend 

 of the potential will be in the negative direction. This is of great sig- 

 nificance for an understanding of the varied catalytic effects of the 

 different oxidation-reduction systems which form part of the enzyme 

 systems. In the same manner as the Fe-porphyrins, and its nitrogenous 

 complexes give a series of oxidation-reduction systems, the potentials 

 of the pyridine nucleotides and flavins in combination with different 

 proteins may change, at constant pK, according to the value of the dis- 

 sociation constants of the protein complex. 



The breakdown of foodstuffs in stepwise manner is facilitated by the 

 interposition of reversible oxidation-reduction enzymatic systems, and 

 the stepwise transfer of electrons is facilitated by the property of the 

 three main electron-transfer systems (pyridine nucleotides, flavins, Fe- 

 porphyrins) of forming reversible complex compounds with proteins 

 with a wide variety of oxidation-reduction potentials. It must be re- 

 called, however, that electron transfer between two reversible enzymatic 

 systems does not occur but through the mediation of electroactive sys- 

 tems as shown by the experiments of Borsook (Table IX) (17). 



The Pyruvate Oxidative Pathway 



Of all the foodstuffs, carbohydrate provides most free useful energy 

 in its breakdown. It is mainly carbohydrate-provided energy which is 

 used during the process of embryonic growth and development. In gen- 

 eral, carbohydrate breakdown occurs in two phases : the anaerobic phase 

 which ends in pyruvic acid formation, and the oxidative phase which 

 involves the utilization of pyruvate via the oxidative pathway. In 1932 

 Barron and Miller (11) found that pyruvate was oxidized to acetate 

 and CO2 by gonococci. Although formation of acetate from pyruvate 

 by animal tissues has also been reported (46, 84, 55), there is a tendency 

 to ignore this oxidative pathway of pyruvate metabolism and to give as 

 the main oxidative pathway that of pyruvate carboxylation to oxaloace- 

 tate and condensation between pyruvate and oxaloacetate, as indicated 

 by Krebs in his "tricarboxylic acid cycle" (45). The powerful inhibit- 

 ing effect of fluoroacetate on the oxidation of acetate was used by Bart- 

 lett, Ahrens, and Barron ( 14) to test the oxidative pathway of pyruvate 

 metabolism. To discover this oxidative pathway fluoroacetate is indeed 

 the ideal agent, since if acetate is formed during the metabolism of 

 pyruvate, and it normally disappears in condensation reactions (acetyla- 



