414 2. ANALOGS OF ENZYME REACTION COMPONENTS 



tose-6-P but inhibits the second reaction noncompetitively with respect to 

 sedoheptulose-7-P or glyceraldehyde-3-P. Since the ^/s are roughly the 

 same for all inhibitions (around 60 vnM), a single binding site for phosphate 

 was postulated. Phosphate prevents the formation of the transaldolase- 

 dihydroxyacetone complex but does not interfere with the transfer of the 

 dihydroxyacetone to its acceptor. 



Multivalent anions in general are inhibitors of glycolysis. The anaerobic 

 formation of lactate from glucose in pigeon hemoly sates is depressed 84% 

 by 40 mM sulfate, 64% by 20 mM phosphate, 100% by 4.2 mM oxalate, 

 and 48% by 0.1% ribonucleate (Dische and Ashwell, 1955). The reactions 

 from glucose -^ lactate are inhibited more strongly than from fructose-1,6- 

 diP — > lactate; therefore there is inhibition previous to fructose-l,6-diP. The 

 sequence from glucose -^ glyceraldehyde-3-P is inhibited strongly by sulfate 

 and ribonucleate. Aldolase is inhibited about 20% by 40 mM sulfate but is 

 not affected by oxalate. It was concluded that there are three sites of action, 

 the strongest on hexokinase, next on glyceraldehyde-3-P dehydrogenase, 

 and the last possibly on pyruvate kinase, the inhibitions being competitive 

 with ATP or NAD. Actually little positive evidence was provided for these 

 sites and other possibilities are just as likely; furthermore, competition with 

 hexose phosphate and glycerol phosphate is also possible. In addition the 

 complexing of Mg++ by these anions must be considered since several gly- 

 colytic enzymes are activated by this ion. 



It will suffice to mention four additional interesting examples of analog 

 inhibition on this phase of metabolism. Cataractogenic sugars and polyols 

 inhibit lens mutarotase while noncataractogenic sugars do not; the K,'s are 

 4 mM for galactose, 15 mM for xylose, and 100 mM for sorbitol (Keston, 

 1963). Despite the weak inhibitory activity of sorbitol, there is a large 

 amount in the lens in certain conditions, such as diabetes (perhaps around 

 30 mM). Mannose is quite toxic to honeybees; of bees offered 1 M mannose 

 solution, 50% were dead in 90 min and over 90% in 3 hr (Sols et al., 1960 a). 

 It was found that bees have a hexokinase very active toward mannose 

 coupled with a negligible amount of phosphomannose isomerase, so that 

 mannose not only may interfere with phosphorylation of glucose and fruc- 

 tose, but many accumulate as mannose-6-P, which could disturb glycolysis 

 in a number of ways. Xylose appears to be in some manner a specific inhibi- 

 tor of photosynthesis, since Chlorella propagation is not inhibited by 0.5- 

 1.5% xylose when glucose, fructose, or mannose is present (thus it is not 

 inherently toxic), but under photosynthetic conditions the cells rapidly lose 

 their color and ability to divide, an effect that can be reversed by glucose 

 (Hassall, 1958). It was postulated that xylose may compete with xylulose- 

 5-P for an enzyme in the transketolase pathway and block photosynthesis; 

 on the other hand, a phosphorylated product may be the active inhibitor. 

 Analogs without the usual hexose structure may also inhibit glycolysis and 



