CELLULAR AND TISSUE FUNCTION 203 



Single Cell Motility 



A thorough study of the respiration and motility of the ciliate Paramecium 

 caudatum was made by Holland and Humphrey (1953). Malonate at 20 mM 

 inhibits the endogenous respiration 31% but has no effect on the ciHary 

 activity over 1 hr. The oxidation of cycle substrates, such as citrate, a- 

 ketoglutarate, fumarate, and malate, is well inhibited, and it is likely that 

 the cycle is present. Furthermore, the succinate oxidase in homogenates 

 is quite sensitive to malonate. One must conclude either that malonate 

 does not penetrate sufficiently or that the motility is not entirely dependent 

 on the cycle for an energy supply. The answer to this problem may lie in 

 the observation that malonate does not inhibit the oxidation of pyruvate 

 or acetate. Holland and Humphrey point out that there are many alternate 

 pathways for metabolism in paramecia. Thus it is possible that normally 

 energy is derived from the cycle but during a cycle block energy is provid- 

 ed by other alternate reactions. In the human parasitic ciliate Balantidium 

 coli, malonate depresses both respiration, which is probably endogenous, 

 and motility (Agosin and von Brand, 1953). The flagellar motility of Ba- 

 cillus brevis is not affected by 10 mM malonate (De Robertis and Peluffo, 

 1951). The motility of bull sperm is reduced appreciably by 10 mM mal- 

 onate and the endogenous respiration is simultaneously inhibited 55% 

 (Lardy and Phillips, 1945). However, the results are quite different when 

 various substrates are present and motility is depressed very little or not 

 at all. Since motility is not depressed with glucose or pyruvate as sub- 

 strate, whereas it is with acetate, it is likely that energy sources other 

 than the cycle can be used. Ciliary and flagellar activities in different or- 

 ganisms are thus affected in various ways by malonate and no uniform 

 picture emerges from the data at present available. 



Chemotaxis and phagocytosis in guinea pig leucocytes are partially inhi- 

 bited by malonate but the concentration used (140 mM) was so high that 

 little significance can be attached to these results (Lebrun and Delaunay, 

 1951). Bacterial phagocytosis by human neutrophiles is depressed moder- 

 ately by malonate from 33.5 to 100 mM but no effect is seen with 6.7 mM 

 (Berry and Derbyshire, 1956). Malonate at 1 mM has no effect on the mi- 

 gration of amphibian chromatophores in cultures of the neural crest (Flick- 

 inger, 1949). At 10 mM, malonate is toxic to these preparations and not 

 specifically depressant to the motility. These limited results point to a 

 relative insusceptibility of ameboid-type movements to malonate, which is 

 not surprising considering the known metabolic characteristics of such cells. 



Renal Tubular Transport 



Most of the studies of the effects of malonate on the kidney have involved 

 the active transport of p-aminohippurate. The accumulation of this sub- 



