98 The Chemistry of the Injured Cell 



CHEMICAL CHANGES IN AUTOLYSING CELLS 



Autolysing liver shows a steady decrease in its protein nitrogen, 

 RNA and DNA up to forty-eight hours of the onset of autolysis, 

 after which they remain relatively constant. RNA and DNA fall 

 to about six to seven and twelve per cent respectively of their 

 original content. Free amino acids, acid soluble N, acid-soluble P 

 increase up to forty-eight hours, then decline. Lipid content is least 

 changed. 



There is a general loss of cellular enzymes. Thus succinoxidase 

 and cytochrome oxidase activity disappear in twenty-four hours and 

 acid and alkaline phosphatase, esterase and peptidase activity con- 

 tinues to decline over seventy-two hours. The decreased rate of 

 removal of protein after forty-eight hours reflects the declining 

 activity of proteolytic enzymes and this is indicated to some extent 

 by the fairly rapid disappearance of L-leucylglycine peptidase 

 (Berenborn et al. } 1955; Wahi et al., 1955; Gossner, 1955) . 



Release of enzymes from the cell lysosomes has been recently 

 recorded by de Duve and his co-workers (1959) . These minute 

 organelles are present in cell cytoplasm and are of similar size to 

 mitochondria but are distinct from other intracellular particles. In 

 freshly isolated preparations they behave as fragile but intact sacs. 

 When they are injured they release a collection of soluble hydro- 

 lytic enzymes whose activity is maximal at acid reaction. Disruption 

 of their lipoprotein membrane is no doubt responsible for the 

 enzymic leakage. In the ischaemic rat liver, for instance, there is 

 progressive release of the lysosomal hydrolases, acid phosphatase, 

 cathepsin, /? glucuronidase, acid ribonuclease and acid desoxyri- 

 bonuclease. This release reaches a plateau corresponding to the 

 rupture of about 80 per cent of the lysosomes in three to four hours. 

 Cytochrome oxidase activity is reduced to one tenth in six to eight 

 hours, glucose-6-phosphatase about the same in ten to twelve hours, 

 cathepsin and the two acid nucleases reach fifty to sixty per cent 

 activity after about 8 hours, (3 glucuronidase is unaffected for six 

 hours, then increases by about 40 per cent during the next twelve 

 hours and remains elevated while acid phosphatase remains un- 

 changed during the first day and then slowly decreases to about 



