CELLULAR AND TISSUE FUNCTION 209 



as we have seen for kidney and gastric mucosa, and the mechanism may be 

 either a simple reduction in the energy supply or a more direct interference 

 with electron transport associated with ionic movements across the mem- 

 brane. One must also attempt to distinguish between effects on the active 

 transport and increases in permeability. If the permeability to an ion is 

 significantly increased, its intracellular accumulation may drop because the 

 ion pump is no longer able to maintain the normal concentration; such an 

 action would appear superficially to be an inhibition of active transport. 



Malonate up to 10 mM has no effect on the transport of Na+ and K+ 

 across the human erythrocyte membrane (Maizels, 1951), which is not sur- 

 prising since the principal energy source in such cells is glycolytic. In ascites 

 tumor cells, substrates (for example, glucose and succinate) increase the 

 efflux of Na+. Cyanide at a concentration inhibiting respiration 70% has 

 no effect on either the influx or efiiux of Na+, presumably because the rate 

 of aerobic glycolysis is simultaneously doubled, this compensating for the 

 oxidative depression (Maizels et al., 1958). Malonate at 12.5 mM, on the 

 other hand, inhibits respiration 35% but produces only a 5% increase in 

 the glycolysis, which may explain why the rate coefficient for Na+ efflux 

 drops from 6.5 to 5.1 hr-^ The accumulation of intramitochondrial K+ in 

 preparations from rabbit heart is dependent on oxidative phosphorylation 

 but is unaffected by 0.2 mM malonate (Ulrich, 1960). Inasmuch as a-keto- 

 glutarate was the substrate used, even a complete block of succinate oxida- 

 tion might not be expected to have much effect on ion movements because 

 sufficient ATP may be generated in the single-step oxidation of a-keto- 

 glutarate. Ca++ uptake and binding by kidney mitochondria depend on an 

 oxidizable substrate and ATP; it is depressed 75% by 10 mM malonate, 

 which suggests interference with the operation of the cycle, but could 

 relate to the chelation of the Ca++ by the malonate (Vasington and Murphy, 

 1962). The uptake of iodide is inhibited by rather high concentrations of 

 malonate in the brown alga Ascophyllum, nodosum (79% inhibition at 25 mM) 

 (Kelly, 1953), the rabbit ciliary body (50% inhibition at 50 mM) (Becker, 

 1961), and the rabbit choroid plexus (50% inhibition at 20 mM) (Welch, 

 1962), but 1 mM malonate has no effect on the uptake or incorporation of 

 iodide in sheep thyroid particulate fractions (Tong et al., 1957). 



The accumulation of P,^^ in the roots of the loblolly pine Pinus taeda 

 during a 3 hr incubation is inhibited 5% at pH 4.75 but stimulated 54% 

 at pH 5.75 (Kramer, 1951). Similar results are obtained in mycorrhizal 

 root tips but the inhibition is somewhat greater. It is possible that at the 

 concentration (25 mM) of malonate, the stimulation is an ionic effect which 

 is partially counteracted by a malonate inhibition at the lower pH. The 

 uptake of K+ and Br~ by barley roots is quite strongly inhibited by mal- 

 onate at pH 4.5 (see accompanying tabulation) (Ordin and Jacobson, 1955). 

 The inhibition is overcome to some extent by malate and fumarate; sue- 



