696 6. ARSENICALS 



succinyl-CoA normally arises from a-ketoglutarate and arsenicals would 

 potently depress this. It was shown by Lascelles (1956) in RJiodopseudo- 

 monas spheroides, which converts glycine and a-ketoglutarate to porphyrins 

 and bacteriochlorophyll, that arsenite completely blocks the forma- 

 tion of (5-aminolevulinate at a concentration having no effect at all on the 

 further reactions by which (5-aminolevulinate is utilized to yield copropor- 

 phyrin III, and the results of Granick (1958) also indicate a site of inhibition 

 before (5-aminolevulinate in erythrocytes. The only distal step tested directly 

 is the condensation of porphibilinogen to uroporphyrinogen III and it 

 is insensitive to arsenite (Lockwood and Benson, 1960). Studies on the 

 formation of (5-aminolevulinate in liver mitochondria likewise implicate 

 a-ketoglutarate oxidase as a major point of arsenite attack (Granick and 

 Urata, 1963). The effects of arsenite on the synthesis of protoporphyrin 

 by chicken erythrocytes are shown in Fig. II-1-17. It is interesting that 

 there is as much inhibition when glycine and succinate are used as substrates. 

 This could result from inhibition of the formation of succinyl-CoA from 

 succinate, but it also leaves open the possibility that arsenite inhibits 

 (5-aminolevulinate synthetase. This could be easily determined by studying 

 the reaction with succinyl-CoA as the substrate. The observation that arse- 

 nite causes a prolonged excretion of coproporphyrin in rabbits is probably 

 not attributable to an effect directly on porphyrin synthesis, but to some 

 disturbance in liver metabolism (Schwartz and Zagaria, 1951), 



Photosynthesis 



The photolysis of water and the evolution of oxygen are not significantly 

 inhibited by arsenite in Chlorella (Kandler, 1955) or spinach chloroplasts 

 (Arnon et al., 1956), nor is there appreciable inhibition of photophosphoryl- 

 ation in Rhodospirillum rubrum (Geller and Lipmann, 1960), chloroplasts 

 (Arnon et al., 1956, 1959; Whatley et al., 1959), or dahlia and datura leaves 

 (Massini, 1957). These results seem to eliminate the participation of hpoate 

 as the primary reductant in the early photosynthetic events. Enzymes 

 catalyzing the interconversion of NADP and NADPH in chloroplasts 

 are likewise not inhibited (Avron and Jagendorf, 1956; San Pietro and 

 Lang, 1958). The fixation of CO2 by chloroplasts, however, is strongly 

 inhibited by arsenite, as first shown by Arnon et al. (1956), the suppression 

 being complete at a concentration without effect on the Hill reaction or 

 photophosphorylation. This has been studied by Gibbs and Calo (1959 

 a, b, 1960 b), who obtained inhibitions of around 90% for the photochemical 

 reduction of CO2 in reconstituted chloroplast systems with 0.01 mM 

 arsenite (whole chloroplasts are less than one tenth as sensitive). None 

 of the enzymes involved in the conversion of COg to carbohydrate is inhibited 

 by arsenite at 1 mM, so the site for the block is unknown. The hypothetical 

 primary photogenic substance postulated by Miyachi (1960) to play a 



