406 2. ANALOGS OF ENZYME REACTION COMPONENTS 



C-1 of D-glucopyranose and C-2 of D-fructopyranose are different, (3) 

 there is a primary alcohol group on the C-5 of glucose but not on the C-6 

 of fructose, and (4) the /?-anomer of fructose may predominate. 



An interesting type of inhibition on the phosphorolysis of starch by 

 monofluorophosphate was observed by Rapp and Sliwinski (1956). The 



0- o- 



-O— P+— OH -0— P+— F 



o- o- 



Orthophosphate Monofluorophosphate 



sizes and electronic configurations of orthophosphate and monofluoro- 

 phosphate are quite similar so that interference with many reactions in- 

 volving phosphate might be anticipated. The inhibition of potato phosphory- 

 lase is completely competitive {Kj„ = 3.2 mM and K, = 2.8 mM calculated 

 from their ijv-ijiS) plot) and the affinity of the enzyme for the two substances 

 corresponds to this tectonic resemblance. The inhibition is not due to the 

 release of fluoride since 20 mM fluoride inhibits only 6.4% and 2.1 mM 

 monofluorophosphate inhibits 50%. 



Phosphoglucose Isomerase 



This enzyme is important in regulating carbohydrate metabolism since 

 its activity, along with other factors, determines how much glucose-6-P 

 enters the glycolytic pathway; in other words, this enzyme represents a 

 branching point of metabolism in the terminology of Krebs. We have seen 

 that inhibition by 2-DG-6-P is probably an important component of the 

 mechanism of action of 2-DG. The potent inhibition by 6-phosphogluconate 

 is particularly interesting because this substance is formed from glucose-6-P 

 in the pentose phosphate pathway and could determine to some extent the 

 diversion at the branching point. Parr (1956, 1957) reported inhibition of the 

 enzymes from blood, liver, muscle, and potato and found it to be competi- 

 tive; in the reaction glucose-6-P -> fructose-6-P, 1 mM inhibits 75% and 



fructose-6-P »^ glycolytic pathway 



Glucose »- glucose-6-P 



-phosphogluconate ■*- pentose- P pathway 



2 mM 95% (glucose-6-P 2 mM). Similar competitive inhibitions of the en- 

 zymes from yeast (Noltmann and Bruns, 1959) and Trichinella spiralis 

 (Mancilla and Agosin, 1960) have been noted. Rabbit muscle phosphoglu- 

 cose isomerase may be even more sensitive to 6-phosphogluconate, since the 



