EFFECTS ON GLYCOLYSIS 481 



EFFECTS ON GLYCOLYSIS 



Quinones frequently inhibit glycolysis strongly and it is likely that 

 this plays an important role in their actions on certain organisms and tis- 

 sues. Some results are summarized in Table 5-4 and certain tentative con- 

 clusions may be drawn: (1) the glycolytic inhibition is occasionally very 

 potent; (2) there is a good deal of variation in response between different 

 organisms and tissues; (3) the naphthoquinones are generally more potent 

 inhibitors than the benzoquinones; (4) there is often a diphasic effect with 

 stimulation at lower concentrations; and (5) aerobic glycolysis seems to 

 be more sensitive than anaerobic glycolysis to the quinones, although this 

 may be due mainly to the fact that the inhibitory form is the quinone and 

 not the hydroquinone. Aerobic lactate formation may be decreased, unaf- 

 fected, or increased, probably depending on the balance of action on the 

 glycolytic and oxidative pathways, and on the magnitude of the Pasteur- 

 Crabtree interactions in the particular tissue. Over-all glucose utilization 

 is strongly depressed both anaerobically and aerobically. The inhibition of 

 glucose uptake by Schistosoma was found to be greater than the inhibition 

 of aerobic glycolysis (Bueding, 1950; Bueding et al, 1947), and the utili- 

 zation of glucose by Fusarium is markedly reduced by 1,4-naphthoquinone, 

 definite effects being exerted at 0.0063 mM (Maselli and Nord, 1952). 

 It is interesting that injections of menadione in rats lead to a mean fall in 

 liver glycogen from 15.3 mg/g to 0.9 mg/g in 20-50 min (Schulz and Goss, 

 1956), but it is not known whether this is due to a block in glycogen for- 

 mation or to a stimulation of its utilization by some mechanism. Glycogen 

 formation in yeast in strongly depressed by various quinones, the most 

 potent, 1,4-naphthoquinone, inhibiting 55% at 0.01 mM (Hoffmann-Osten- 

 hof and Kriz, 1949 b), but even here it is not certain if this may not be 

 partly due to increased breakdown. 



The major site for the glycolytic inhibition has not been definitely 

 established. Inspection of Table 5-2 shows only two enzymes of the EM 

 pathway, hexokinase and 3-phosphoglyceraldehyde dehydrogenase, to have 

 been directly studied and both to be readily inhibited. Some analysis of the 

 site of action was undertaken by Meyerhof and Randall (1948) in brain 

 extracts. The inhibition of glycolysis by p-benzoquinone and various 1,2 

 naphthoquinones is greater with glucose than with fructose-l,6-diP as 

 the substrate, and they concluded that at least part of the glycolytic in- 

 hibition must be on hexokinase. However, the inhibition when glucose-6-P 

 is the substrate is also high so that perhaps some action on phosphohexo- 

 kinase is suggested. Hochstein and Cohen (1960 b) reported different 

 results in brain homogenates in that the inhibitions by p-benzoquinone 

 and menadione are the same for both glucose and fructose- 1,6-diP, but 

 when 3-P-glycerate is the substrate the inhibition is definitely less, implicat- 

 ing the 3-phosphoglyceraldehyde dehydrogenase as the major site of attack. 



