Cellular Metabolism 



73 



FRUCTOSE 

 +ATP 



GLUCOSE 



+ATP 



GLYCOGEN 

 + P 



Fructose- 6- phosphate^Glucose- 6-phosphate^ Glucose- 1-phosphate 



i ATP 

 Fructose- 1,6- diphosphate 



Inhibited 

 by lAA 



Inhibited 

 by NaF 



Triosephosphate^DPN^Flavoprotein I ?->Cyt. C^Cyt. ox.-^O, 



Phosphoglyceric acid 

 Phosphopyruvic acid 

 Pyruvic acid 



^ ? 



-^ Cytochrome system-^ 0^ 



Acetyl 



|+oaa| i 



Isocitric acid -^ TPN-^Flavoprotein Il-^Cyt. C^Cyt. ox.->02 



Inhibited 

 by arsenite 



Inhibited 

 by malonate 



Oxalosuccinic acid 



cC-Ketoglutaric acid- 



-^ Cyt. C^Cyt. ox.-^O, 



-^ Cyt. C-^Cyt. ox.^O, 



Succinic acid ^? 



Fumaric acid 



i 



Malic acid >DPN^Flavoprotein I ?-9>Cyt. C-^Cyt. ox.-^O 



I 



Oxaloacetic acid 



Fig. 4. Intermediate catalysts involved in the transfer of hydrogen and electrons to molecular oxygen in 

 the stepwise oxidation of carbohydrate in muscle. Abbreviations: lAA, iodoacetic acid; OAA, oxaloacetic 

 acid; Cyt. C, cytochrome c; Cyt. ox., cytochrome oxidase. 



The factor of Lockhart and Potter, and Altschul et al. is referred to as Flavoprotein I with a question 

 mark. This factor is specific for DPN. Flavoprotein II, specific for TPN, is the cytochrome reductase of 

 Haas, Horecker, and Hogness. Whether cytochromes a and b are involved in any of the steps is not definitely 

 known. The important discovery has recently been made that the phosphorylation of glucose by ATP to 

 glucose-6-phosphate, catalyzed by the enzyme hexokinase, is under the dual control of hormones from the 

 anterior pituitary and adrenal cortex on one side, and insulin on the other. (From Ochoa, '47.) 



later give the sugar a preliminary working over to 

 result in the phosphorylated form shown. Direct 

 oxidation without preliminary phosphorylation pos- 

 sibly may also occur (cf. Barron, '43), but its phys- 

 iological role is still to be established. The usual 

 hexose for the scheme shown would be glucose. 

 There is evidence that other sugars may also enter 

 the system provided the appropriate enzymes are 

 present (cf. Lardy, '50). 



A preliminary splitting of the 1,6-fructose diphos- 

 phate leads to the formation of two triose monophos- 

 phates, which, in the presence of triose isomerase, 

 are interconvertible. The phosphoglyceraldehyde 

 formed, in the presence of phosphate and a phos- 

 phate acceptor (ADP). is then oxidized by phos- 

 phoglyceraldehyde oxidase to yield phosphoglyceric 

 acid and ATP. 



At this important step, two ubiquitous coenzyme 



systems are introduced: the pyridine nucleotide* 

 coenzymes (cf. LePage, in Lardy, '50) concerned 

 with hydrogen transport, and the adenylic acid 

 system! (ATP and ADP) concerned with energy 

 packet storage and transp ort. For the reaction to be 



* The diphosphopyridine nucleotide is best known 

 and will be referred to as oxidized (DPN) or re- 

 duced (DPNHo) coenzyme. This is the coenzyme I 

 of Warburg. 



f Adenylic acid is a nucleotide containing one 

 phosphate group per molecule. This form (adeno- 

 sine monophosphate, or AMP) can add phosphate 

 by energy-rich bonds (cf. Lipmann, '41) to form 

 adenosine diphosphate (ADP) or adenosine triphos- 

 phate (ATP). In most of the discussion that will 

 follow, only the change ADP -f P t"^ ATP will 

 be considered, although the other forms may also be 

 concerned. 



