102 THE BIOCHEMISTRY OF B VITAMINS 



to favor a net change, which is the forward reaction. As a corollary, there 

 should be some critical set of conditions for a reaction in which there is no 

 net change, in which case the system will be at equilibrium. 



In the past the reversibility of many enzymatic reactions has been 

 frequently questioned, since attempts to demonstrate enzymatic syn- 

 thesis, as opposed to hydrolysis and other forms of degradation, in a 

 direct manner have in some cases proved wholly unsuccessful. Even if 

 a catalyst is present in excess it may be impossible to achieve the con- 

 centrations of products required to produce a measurable resynthesis of 

 the original substances. Today, with isotopes available, it is easy to 

 demonstrate that in uncomplicated enzymatic reactions the products are 

 in dynamic equilibrium with the reactants, even though it is sometimes 

 impossible to achieve the conditions necessary to completely effect the 

 reverse reaction. This can best be shown by labelling one of the products 

 with an isotopic atom, adding it to an enzyme system during the course 

 of a reaction, and stopping the reaction while there is still some of the 

 reactant left. If the reactant contains some of the isotopic element added 

 in the product, then it is obvious that the "backward reaction" has been 

 taking place. 



Consequently, today the question should not be, "Is this enzyme re- 

 action reversible?" but, "Do the conditions required for reversing this 

 reaction occur or can they be achieved?" To answer the latter question 

 it is necessary to know the relative concentration of reactants and 

 products when they are at equilibrium. At equilibrium a reaction can be 

 forced to go in either direction by making only slight changes in the 

 concentration of one of the participating substances. In cells a number 

 of reactions mediated by enzyme systems, including many of these con- 

 taining B vitamins, are at equilibrium most of the time. The direction in 

 which these reactions proceed may be constantly alternating because of 

 the slight changes produced by other reactions in cells. In the reaction, 

 glycogen + H 3 P0 4 +± glucose- 1 -phosphate, only slight changes in the 

 intracellular concentration of inorganic phosphate are needed to stop 

 the process in which glycogen is utilized and to initiate its synthesis. This 

 is an example of one of the important methods by which metabolic proc- 

 esses are regulated. It is also possible to find reactions at the other 

 extremes — hydrolytic reactions and some decarboxylations are good ex- 

 amples. Here, even though the catalyst is present, the ratio of the concen- 

 trations of products to reactants at equilibrium is so large that it is 

 impossible to achieve the concentration of the products needed to reverse 

 the reaction effectively. 



A knowledge of relative concentrations at equilibrium is not only of 

 value in understanding or predicting the mechanisms and chemical routes 



