A Proposed Mechanism for the Effects of Saccharin on Glucose Metabolism by Streptococcus mutans

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Abstract
Saccharin inhibited the rate of growth, the amount of acid produced, and glucose utilization by Streptococcus mutans NCTC 10449. One possible mechanism by which saccharin mediates its negative effects upon glucose catabolism is by inhibiting lactate dehydrogenase, the enzyme which catalyzes the terminal, regulatory step in the Embden-Meyerhof-Parnas pathway. The inhibition of lactate dehydrogenase activity by saccharin is dependent upon the fact that it competitively inhibits the binding of its reduced coenzyme, NADH, to the enzyme. The Ki values for saccharin estimated from Dixon plot analysis is 6.2 mM and the inhibitor increased the Km value of NADH from 0.033 to 0.250 mM. In contrast, saccharin had no effect upon the interaction of either its allosteric effector, fructose-1,6-diphosphate, or its substrate pyruvate, with the enzyme. Lactate dehydrogenases assayed in cell-free extracts obtained from members of other S. mutans serotype groups and other oral streptococcal species were also inhibited by saccharin. Saccharin also served to inhibit NAD(H)- and NADP(H)-dependent oxidoreductases in addition to lactate dehydrogenase when assayed in cell-free extracts from S. mutans NCTC 10449 and Streptococcus faecalis. Thus, the saccharin-mediated inhibition of pyridine nucleotide-dependent oxidoreductases may be one manner by which it effects glucose metabolism by this organism.