410 



2. ANALOGS OF ENZYME REACTION COMPONENTS 



COO- 



HCOP03H- 

 H2COH 



D-2-Phosphoglycerate 



coo- 



I 



CH, 



H2COPO3H- 



/9-Hydroxypropionate-P 



coo- 



HCOH 



H2COPO3H- 

 D -3 - Phosphogly cerate 



coo- 



HCOPO3H- 

 HCOH 



CH3 



D-er7/<A/-o-2,3-Dihydroxy- 

 butvrate-2-P 



COO- 



HCOP03H- 

 CH3 



D-Phospholactate 



coo- 



HCOH 

 HCOPO3H- 



CH3 



T>-erythro-2,Z-T)'\\ry- 

 droxybutyrate-3-P 



mately 1.2 kcal/mole. This would indicate that 2- and 3-phosphates fit 

 comparably as long as there is no bulky group on the 3-position, but when 

 there is it sterically interferes with the bending of the 3-phosphate to fit the 

 active site. 



Glucose and Glucose-6-P Dehydrogenases 



Beef liver glucose dehydrogenase is inhibited strongly and competitively 

 by glucose-6-P (Strecker and Korkes, 1952) and fructose- 1,6-diP (Brink, 

 1953 a), the K-b being 0.0025 mM and 0.062 mM, respectively. The K^ 

 for glucose is around 31 mM at pH 7, so that if this represents a dissociation 

 constant the phosphorylated compounds are bound much more tightly 

 (around 5.8 kcal/mole). The rat liver enzyme is similarly inhibited: glucose- 

 6-P at 0.015 mM inhibits 78% when glucose is 200 mM (Metzger et al, 

 1964). Glucose-1-P also inhibits but is about one-tenth as effective as glu- 

 cose-6-P. Ribose-5-P and fructose-6-P are also less inhibitory (Brink, 1953 a). 

 The potency of the glucose-6-P inhibition is surprising and it is quite likely 

 that it may be important in metabolic regulation or conserving glucose for 

 phosphorylation. Not enough is known about this enzyme or the reaction 

 mechanism to speculate on the nature of the interaction of these inhibitors. 



