482 9. INHIBITION IN CELLS AND TISSUES 



reason one would espect the tissues to respond in different ways to inhibi- 

 tors of metabolism. Differences become even greater when the microorgan- 

 isms that invade our tissues are also considered. The concentrations of 

 substrates, intermediates, and coenzymes vary from tissue to tissue, and 

 depend upon the blood supply, the permeability characteristics, and the 

 nature of the metabolism. Marked variations in glucose content of tissues 

 have been demonstrated by Gey (1956) in the rat (see tabulation). The 



effects of inhibitors acting on glucose metabolism may differ because of 

 this factor alone, as well as being dependent on the different activities 

 of the metabolism that help determine these variations in glucose. The 

 very high concentration of 2,3-diphosphoglycerate in erythrocytes (1.57 

 milf) which is unique to these cells, could well determine the nature of the 

 response to certain inhibitors (Bartlett et al., 1953) and serves as an exam- 

 ple of the great biochemical variety to be expected. The intracellular con- 

 centration of a substrate or intermediate is of particular importance in 

 determining the effect produced by a competitive inhibitor. 



The most fundamental reason for metabolic divergence between tissues 

 is j)robably to be sought in the widely varying relative concentrations of 

 the various enzymes. An excellent table of such relative concentrations 

 is given by Dixon and Webb (1958, p. 642). Especially detailed analyses 

 have recently been made of enzymes in the anatomically distinguishable 

 regions of the central nervous system. 



The distribution of glutamic-y-aminobutyric transaminase in tlie nerv- 

 ous system of the Rhesus monkey is very interesting and certainly re- 

 lated to the functional differences and susceptibility to metabolic inhibition 

 (Salvador and Albers, 1959). In some regions (optic stalk, lateral pyramids, 

 fasciculus gracilis) none could be detected, while in other regions the 

 values ranged widely: globus pallidus, 52; red nucleus, 62; reticular forma- 

 tion, 113; anterior hypothalamic nucleus, 149; inferior colliculus, 219, and 

 inferior olivary nucleus, 294. There is very little in the peripheral regions, 

 such as the spinal cord or ganglia. Within the cortex the enzyme is present 



