CELLULAR AND TISSUE FUNCTION 207 



clear increase in phosphate excretion with a fall in plasma phosphate was 

 also observed. 



The effects of malonate on the renal excretion of malate are interesting, 

 but it is not known if this phenomenon is related to an action on transport 

 mechanisms or to more general metabolic effects. Vishwakarma (1957, 

 1962) showed that malonate has no effect on the excretion df malate in- 

 duced by malate infusion. However, when succinate is infused, the in- 

 creased malate excretion is due to both an increased filtration and a marked 

 tubular secretion. Malonate inhibits the tubular secretion of malate and 

 converts the excretion to a purely filtration process or causes a net resorp- 

 tion. Vishwakarma and Lotspeich (1960) continued this study in chickens 

 and found that when malonate is infused with succinate, instead of block- 

 ing the formation of malate, it further increases the malate excretion. 

 Malonate was infused at a rate of about 6.8 //moles/kg/min. This could 

 mean that malonate (1) enhances the formation of malate from succinate, 

 (2) facilitates the tubular secretion of malate, or (3) gives rise to malate by 

 metabolic conversion. Since malonate infused alone did not significantly 

 increase malate excretion, the last explanation is unlikely. In the dog, mal- 

 onate inhibits the tubular secretion rather than stimulating it and does not 

 inhibit the resorption of malate. The mechanism for this paradoxical effect 

 is unknown. Reference may be made to studies of Lotspeich and Woron- 

 kow (1964), who unilaterally perfused chicken kidneys and found complex 

 effects on the excretions of various organic acids, and concluded that the 

 cycle must be involved in some manner. 



Transintestinal Transport 



Quastel has studied the effects of various inhibitors on the transfer of 

 glucose across the guinea pig intestinal wall. This is an active transport 

 and depends strongly on the aerobic metabolism (as shown by the marked 

 inhibition by cyanide and azide) and the associated phosphorylations (as 

 shown by the 2,4-dinitrophenol inhibition). When malonate at 20 mM is 

 present in the lumen, there is 18.5% inhibition of the glucose transported, 

 but if malonate is present both inside and outside, the inhibition is 44.3% 

 (Darlington and Quastel, 1953). An increase of K"'" from 6 to 15.6 n\M ac- 

 celerates glucose transport about 50%. Malonate inhibits the K^-stimulated 

 transport completely at concentrations as low as 2 mM (Riklis and Quastel, 

 1958). This result may be related to the greater sensitivity of K+-stimulated 

 brain slices to malonate. It was claimed that 20 mM malonate depresses 

 both the accumulation of L-monoiodotyrosine-I^^^ in the intestinal cells and 

 its transport across the intestine, but no data were given (Nathans et al., 

 1960). There is a marked difference between transintestinal transport and 

 tissue accumulation of triiodothyroacetate, the former being inhibited much 



