302 2. MALE ATE 



In both instances, fumarate inhibits fairly potently. The fact that maleate 

 inhibits the oxidation of several cycle substrates but has little effect on 

 succinate in kidney mitochondria led Angielski and Rogulski (1962) to 

 suggest that the inhibition may be on the transfer of electrons to or from 

 NAD. No direct evidence was presented and, since there appears to be no 

 studies of the effect of maleate on enzymes oxidizing NADH, any accept- 

 ance of this hypothesis must be tentative. 



EFFECTS ON RESPIRATION AND GLYCOLYSIS 



The respiratory response to maleate is frequently complicated by the 

 metabolic utilization of the maleate by the tissue (see page 311) and in 

 most cases this factor cannot be quantitatively evaluated. Respiration often 

 is stimulated in plant tissues where metabolism of maleate has been demon- 

 strated, but in animal tissues depression of respiration is the rule, although 

 there is no way of telling if such depression is modified by some utilization 

 of maleate. Fumarate, on the other hand, almost invariably accelerates 

 the endogenous respiration of all tissues; the marked difference between 

 fumarate and maleate is best seen in work with animal tissues (Gronvall, 

 1924). From the limited data available, it appears that maleate is as ef- 

 fective as fumarate, or more so, in stimulating root respiration (Lunde- 

 gardh, 1944; Biber and Farbman, 1951). 



The effects of maleate on the respiratory quotient (Table 2-3) are equiv- 

 ocal, inasmuch as Thunberg (1911 a) found a consistent decrease at low 

 concentrations and an increase at very high concentrations in frog muscle, 

 whereas Gronvall (1924) found rather small effects in a variety of tissues 

 at a high concentration (50 mM), although some increase was most com- 

 monly observed. The fall in R. Q. with low maleate concentrations might 

 be due to an inhibition of carbohydrate utilization and indeed a suppression 

 of glucose oxidation has been observed in spermatozoa (Lardy and Phil- 

 lips, 1943 a) and Azotobacter (Line weaver, 1933). Maleate also inhibits 

 the fermentation of glucose by yeast (Jung and Miiller, 1922). The respi- 

 ration of brain slices is inhibited most potently by maleate when glucose 

 is the substrate, and relatively little in the presence of the cycle substrates 

 (Weil-Malherbe, 1938). Thus one might conclude that maleate is able to 

 reduce the utilization of glucose or glycogen. But there is one metabolic 

 response to maleate which, at least superficially, does not fit into this pic- 

 ture; aerobic glycolysis as measured by lactate formation is markedly 

 stimulated, as shown in brain by Weil-Malherbe (1938) and in sperma- 

 tozoa by Lardy and PhiUips (1943 b). This also occurs in embryo tissue, 

 heart, spleen, and Jensen sarcoma, and the stimulation may amount to 

 as much as 100 200%. The effects of maleate on the respiration and aerobic 

 glycolysis of guinea pig brain slices are compared in Fig. 2-2; it is evident 



