238 1. MALONATE 



(Scholefield, 1955). Tartronate is also a competitive inhibitor of the decar- 

 boxylating malate dehydrogenase (malic enzyme) of pigeon liver with a K^ 

 of 0.1 mM, the inhibition being stronger than with malonate (Stickland, 

 1959 b). The carboxylation of pyruvate, catalyzed by the same enzyme, 

 is also strongly inhibited, but there is a large noncompetitive element 

 (Stickland, 1959 a). The inhibition of lactate and malate oxidations and 

 decarboxylations is not surprising since tartronate is structurally similar. 

 Although tartronate occurs in plant and animal tissues to the extent of 

 8-15 //g/g wet weight of tissue, which would correspond to about 0.1 xnM 

 in the tissue water (Veitch and Brierley, 1962), it is doubtful if it could 

 exert a regulatory action on the metabolism. Tartronate is not metabolized 

 in the rat and consequently is near 8 raM in the urine. 



The respiration of guinea pig brain slices is depressed by tartronate at 

 concentrations of 67-75 rcvM (Jowett and Quastel, 1937). The degree of inhi- 

 bition depends on the substrate provided and is maximal with lactate and 

 minimal with pyruvate. Since lactate is probably metabolized through 

 pyruvate, the inhibition here may be mainly on lactate dehydrogenase. 

 However, the anaerobic breakdown of pyruvate and anaerobic glycolysis 

 are also well inhibited. The respiration of Mycohacterium. phlei with lactate 

 as substrate is inhibited 65% with 66 mM tartronate, although the endo- 

 genous respiration is stimulated and the oxidation of glucose unaffected 

 (Edson and Hunter, 1947). This relatively specific effect on lactate dehydro- 

 genase was used by Fiume (1960) to inhibit aerobic glycolysis in tumor cells, 

 inasmuch as lactate dehydrogenase is involved. It was postulated that 

 aerobic glycolysis might be inhibited more strongly in the tumor than in 

 normal tissues, depleting the ATP supply more severely. It was found that 

 tartronate inhibits aerobic glycolysis of the Yoshida ascites hepatoma — 

 26% at 10 mM, 34% at 20 mM, and 58% at 50 mM - but comparisons 

 with normal tissue were not made. 



The inhibition of phosphatases should perhaps also be considered in 

 work with tartronate, since prostatic acid phosphatase is inhibited com- 

 petitively with a K^ of around 50 mM. The inhibition by tartronate is 

 much greater than by malonate and about twice as potent as by ketomal- 

 onate (Kilsheimer and Axelrod, 1957). 



Aminomalonate 



This substance was considered to be a possible substrate for the synthesis 

 of S-aminolevulinate but was found upon examination to be a potent inhib- 

 itor of S-aminolevulinate synthetase (Matthew and Neuberger, 1963). The 

 inhibition of the enzyme from Rhodopseiidomonas spheroides and chicken 

 erythrocytes is competitive; the K, for the bacterial enzyme is 0.0225 mM. 

 Pyridoxal-P is a coenzyme in these systems and the inhibition depends on 

 its concentration. Aminomalonate may be considered to be an analog of 



