EFFECTS ON METABOLISM 403 



vitamin E-deficient diaphragm is more susceptible to alloxan with respect 

 to glucose uptake, glycogenesis, and respiration. 



We turn now to the effects of alloxan on glycolysis, which one would 

 expect to be quite sensitive on the basis of the results with glycolytic en- 

 zymes. Kensler et al. (1942 b) found that alloxan at 0.22 mM is very de- 

 pressant to the fermentation of fructose- 1,6-diP by yeast extracts if the 

 NAD level is low but not if it is high. This could mean that NAD is pro- 

 tecting the SH groups of glyceraldehyde-3-P dehydrogenase, as it is known 

 to do against various SH reagents. Anaerobic glycolysis in frog muscle 

 brei is about 50% reduced by 1.2 mM alloxan and nearly 90% by 2.5 mM 

 (Gemmill, 1947), and aerobic glycolysis of the cornea is depressed 50% 

 by the injection of 2.5 mg alloxan into the anterior chamber (Langham, 

 1953). However, Villasante and Diaz (1950) detected no inhibition of 

 anaerobic glycolysis in dog kidney. Field et al. (1960) examined the for- 

 mation of labeled COg from glucose in human /5-cell tumor tissue. There 

 seems to be a very active pentose-P shunt, but alloxan was claimed to 

 have no effect on the formation of C^^Oa from either glucose- l-C^* or glu- 

 cose-6-C^^ (there is possibly a slight shift toward the pentose-P pathway)*. 

 In addition to the low concentration of alloxan used, there is the possibility 

 that /?-cell tumors are much more resistant to alloxan than normal /5-cells 

 (see page 391). It is not known if glycolysis is significantly affected in the 

 tissues of the whole animal, or which is more vulnerable, the EM pathway 

 or the cycle. The elevation of blood keto acids reported by El Hawary 

 (1955) cannot be attributed to the direct action of alloxan since the values 

 were obtained 48-72 hr after the administration and are certainly the 

 result of insulin deficiency. 



Lipid Metabolism 



Rusch and Kline (1941) studied the effects of various carcinogenic and 

 carcinostatic agents on the oxidation of phospholipids by glutathione or 

 ascorbate. Alloxan inhibits this 28% at 0.35 mM, probably by its oxidation 

 of the catalysts. The only importance of this observation is to demonstrate 

 that alloxan can exert nonenzymic effects on certain oxidation reactions. 

 The inhibition by alloxan of the oxidation of oleate by E. coli reported by 

 Singer and Barron (1945) could be due to an action on the fatty acid helix 

 or the cycle, but one cannot be certain. 



The effects of alloxan on lipid synthesis from acetate in rat liver ho- 

 mogenates are marked and quite interesting (see accompanying tabulation) 

 (Scaife and Migicovsky, 1957). The inhibition of the incorporation of acetate 



* They state that 0.01 iiig alloxan was placed in each flask in a Dubnoff shaker. 

 The volume was not given but if one assumes 10 ml, the alloxan concentration was 

 0.007 mM, which would hardly be expected to produce much effect. 



