72 The Chemistry of the Injured Cell 



An alternative pathway for glucose metabolism is available 

 through the hexose monophosphate shunt. This is present for cer- 

 tain in the cells of the liver, mammary gland and adipose tissue 

 (Abraham et al., 1954). Glucose-6-phosphate is oxidised to phos- 

 phogluconic acid coupled with the reduction of the pyridine nu- 

 cleotide, TPN. The acid is then decarboxylated "to give pentose 

 sugars which are broken down to C0 2 and water by way of the 

 triose sugars (See Fig. 5) . 



Aerobic metabolism is largely concentrated within the mito- 

 chondria which are the chief site of the tricarboxylic (Krebs) cycle 

 (Fig. 6) . Isolated mitochondria, for instance, can catalyse the 

 oxidation of a number of Krebs cycle intermediates and of fatty 

 acids (Kennedy and Lehninger, 1949) . The Ochoa system that 

 couples phosphorylation with oxidation is also present in the mito- 

 chondria while succinic dehydrogenase and fumarase are generally 

 accepted as enzymes exclusive to mitochondria (Schneider, 1959). 

 Glutamic dehydrogenase which oxidises glutamic acid to a-keto- 

 glutaric acid occurs exclusively in the mitochondria. Other oxida- 

 tions placed there include those of fatty acids and choline, through 

 betaine aldehyde to betaine. The distribution of some of the other 

 enzymes of the cycle in the cell is still imperfectly known. 



Electron carriers are involved in the secondary phases of oxida- 

 tion (Fig. 3) . Cytochrome oxidase is the only one of the substances 

 so concerned that is known to be present exclusively in the mito- 

 chondria. About 10 per cent of the total cell diphosphopyridine 

 nucleotide (DPN) is found in these organelles either firmly bound 

 within them or attached to their membranes (Glock and McLean, 

 1955; Jacobson and Kaplan, 1957) . The DPNH- and TPNH-cyto- 

 chrome c phosphatases are also located in the mitochondria, but 

 large amounts are found within the microsome fraction. Cyto- 

 chrome c is largely associated with the mitochondria and cyto- 

 chrome b and d have been detected there. 



THE ANTI-METABOLIC ACTION OF SOME TOXIC 



SUBSTANCES 



A wide variety of cytotoxic agents have now been studied and 

 many of these exert their effects by damaging respiratory and bio- 

 synthetic mechanisms in the cell. These include such diverse sub- 



