396 



8. INHIBITOR DISTRIBtJTION IN LIVING ORGANISMS 



centrations do not reflect the probably marked variations in concentra- 

 tion between different cells of a tissue or different parts of a cell; in other 

 words, the concentration of inhibitor in the enzyme region may be quite 

 unrelated to the results of gross analysis. In the second place, most of 

 the inhibitor present after long exposures is not combined with enyzme 

 but with many other components of the cells. The figures are really not 

 concentrations in the sense in which (I) is used in kinetic equations. The 

 reason a high tissue uptake of an inhibitor occurs may be unrelated to any 

 enzymic or metabolic factors; cells containing much high-sulf hydryl protein 

 might well accumulate inhibitors such as arsenite and yet the concentration 

 of inhibitor acting on a particular enzyme would be the same, or even less, 

 than in other cells. To illustrate this in another way, the kidney /plasma con- 

 centration ratio for Hg^"^, administered to rats as the diuretic chlor- 

 merodrin, increases steadily: 53 at 1-2 hr, 351 at 3-6 hr, 470 at 12 hr, and 

 975 at 18-24 hr (Giebisch and Dorman 1958). This does not imply that the 

 concentration of mercurial, active against enzymes, has risen during this 



Table 8-2 

 Distribution of Enzyme Inhibitors in the Central Nervous System 



° Isoniazid-C^*: intraperitoneal injection of 10 mg/kg in cats. From Barlow et al. 

 (1957). 



* Diamox-S'^ (acetazolamide): intravenous injection of 150 mg/kg in cats. From 

 Roth et al., (1959). When the region borders on the ventricles, analyses for the cen- 

 tral portion are given inasmuch as the relatively high concentration in the cerebro- 

 spinal fluid introduces inhibitor into the ventricular surfaces. 



