Tm-limited renal tubular reabsorption and the genetics of renal glucosuria

Abstract

Using the principles of enzyme kinetics, an expression is derived for the rate of reabsorption of glucose in a model nephron in which water is being re-absorbed iso-osmotically. Rates are calculated and curves plotted for various plasma glucose concentrations and for different values of two parameters, one ( E) corresponding to the amount of carrier substance per unit area of tubule wall, the other ( K m ) related to the affinity of glucose for the carrier. One such curve closely resembles experimental results in normal humans; a second curve, different only in that E is given half the value, resembles the experimental result in individuals with type A renal glucosuria; a third curve, in which the value of K m is altered, resembles that found in type B renal glucosuria. It is suggested that biosynthesis of the carrier substance is under the control of a pair of autosomal genes, that individuals with type A renal glucosuria are heterozygous for the normal gene and a silent gene, and so have half the normal amount of carrier substance, and that individuals with type B renal glucosuria are heterozygous for the normal gene and a mutant gene controlling the synthesis of a carrier substance with a lower affinity for glucose. The genetics of renal glucosuria are consistent with this theory.