262 2. ANALOGS OF ENZYME REACTION COMPONENTS 



membrane transport may exhibit competitive kinetics. The kinetics will 

 often depend on whether the transport is limiting the metabolic utilization 

 of the substrate or not. Membrane transport involving a carrier (C) molecule 

 can often be represented by: 



S + C ^ SCo -> SC, -► C + S (2-12) 



where the subscripts refer to the outside and inside of the membrane. The 

 later reactions may be written in one direction only because of the utili- 

 zation of the substrate as it enters the cell. If an analog also combines 

 with the carrier: 



S' + C ^ S'C (2-13) 



whether it is transported into the cell or not, typical competitive behavior 

 will be observed since the forms of Eqs. 2-12 and 2-13 are the same as 

 those for competitive enzyme inhibition. 



Plots of transport rates against the external concentrations of the trans- 

 ported substance usually yield hyperbolic curves, and double reciprocal 

 plots are often linear, allowing the calculation of a constant which corres- 

 ponds to the Michaelis-Menten constant in enzyme kinetics. It is frequently 

 assumed that this is the dissociation constant for the complex of the sub- 

 stance with the carrier, but it is not necessarily true for the same reasons 

 that K^,^ is not always K,. The kinetics of transport inhibition are likewise 

 commonly similar to those observed with enzymes and values of K^ may 

 be determined by appropriate plotting, this constant representing the dis- 

 sociation constant of the carrier-analog complex. The kinetics of carrier 

 transport and its inhibition have been elaborated by Wilbrandt and Rosen- 

 berg (1961) and Rosenberg and Wilbrandt (1962) for facilitated diffusion 

 and certain restricted types of active transport. It is interesting in connec- 

 tion with certain types of inhibition work to note that the accumulation 

 ratio, (X),/(X)^ = VJkK„j, where F^„ is the maximal transport rate, K,„ 

 is the Michaelis-Menten constant for transport, and k is the passive diffu- 

 sion constant for the membrane. Thus the cell/medium ratio may be altered 

 by the inhibitor as a result of changes in any of these three parameters. 



Carbohydrate Transport 



Competition between sugars for entrance into cells has been observed 

 in many tissues but has seldom been studied quantitatively, so that in most 

 cases it is impossible to know if true competition kinetics are followed. 

 Occasionally a reduction in the inhibition with increase in the concentration 

 of the transported substrate has been noted; for example, the active ac- 

 cumulation of D-galactose by rabbit kidney cortex slices is inhibited 61% 

 by 5.6 rciM glucose when D-galactose is 0.1 mM and only 28% when d- 

 galactose is 0.2 mM (Krane and Crane, 1959), but these results do not fit 



