286 2. MALEATE 



(1924) to several tissues of various animals, in which fumarate stimulated 

 the respiration and maleate depressed it at identical concentrations. When 

 the competitive action of malonate against succinate oxidation became 

 known, it was easy for Gozsy and Szent-Gyorgyi (1934) to postulate without 

 evidence that maleate is related to fumarate as malonate to succinate, 

 in order to explain the inhibition of muscle respiration by maleate and other 

 reported effects for which no data were given. The relationship between 

 maleate and fumarate is, of course, entirely different from that between 

 malonate and succinate, and it was soon shown by Morgan and Friedmann 

 (1938 b) that the inhibition of metabolism and of several enzymes by 

 maleate is due primarily to the ability to react with SH groups, and more 

 recently Massey (1953 b) has shown fumarase to have a low affinity for 

 maleate. The generally irreversible nature of the inhibition also points 

 to a chemical reaction rather than a simple competitive effect due to its 

 structural similarity to other dicarboxylic acids, although we shall see 

 that competitive behavior is occasionally observed. 



During the past 20 years maleate has been shown to exert some very 

 interesting actions on biological systems, but it is difficult in any case to 

 ascribe its action to a definite and specific inhibition of a particular enzyme. 

 When a comparative estimate of the sensitivities of various enzymes to 

 maleate can eventually be made, these problems may be solved. In fact, 

 it is not clear if maleate actually occurs naturally in living tissues; it has 

 usually been stated that it does not, even in certain plants and fruits in 

 which all the related acids occur (e. g., Schmalfuss and Keitel, 1924). 

 Copisarow (1936) obtained a substance from apples (named "blastokolin") 

 which inhibited ripening and germination in certain fruits and potatoes 

 in a manner similar to maleate, and thought that the natural inhibitor 

 might be maleate. Maleic acid has been found in Portuguese wines to the 

 extent of 1.5 g/liter, but this does not imply that it is present in the grapes 

 (Correia and Sergio, 1943). Marinov (1950) reported that maleate occurs 

 in potato plants and increases during infection with mosaic virus. Maleate 

 has not been certainly detected in animal tissues, but a thorough search 

 with sensitive methods has not been done, and since various maleyl deriva- 

 tives are now known to be intermediates in metabolism and new enzymes 

 have been reported for the metabolism of maleate, it seems likely that at 

 least low concentrations may be present (see page 313). Maleate is an 

 interesting inhibitor and merits more serious investigation, particularly 

 with respect to its renal actions and antimitotic potential. 



CHEMICAL PROPERTIES 



The physical and chemical properties of maleic acid differ markedly from 

 those of fumaric acid, since the position of the carboxyl groups is a major 



