Sulfhydryl groups and gastric acid secretion.

Abstract

Gastric acid secretion is inhibited by reagents attacking sulfhydryl groups: iodoacetate amide (IAAm), N-ethyl maleimide (NEM), p-chloromercuribenzoate (ClHgB) and various forms of trivalent arsenic. An attempt was made to discover the nature of the group attacked by studying the effect of these and other reagents upon four sulfhydryl systems of the stomach: succinoxidase, glutathione (GSH), coenzyme A (CoA) and lipoic acid. Succinoxidase activity is reduced only slightly by treatment with IAAm or NEM which severely inhibits secretion. Both the enzyme system and secretion are inhibited by 2,3-dimercaptopropanol (BAL). Neither malonate nor succinate affects acid secretion or oxygen uptake under conditions designed to facilitate their entrance into cells. Succinoxidase activity in extracts of stomachs is only slightly if at all affected by prior stimulation of the stomach to secrete. GSH is reduced by IAAm or NEM. Addition of GSH does not reverse inhibition. GSH oxidase is absent from extracts, but the stomach reduces GSSG. Extracts contain methyl glyoxalase, but addition of crude methyl glyoxal inhibits acid secretion. CoA is reduced by NEM parallel with NEM's effect on secretion. IAAm has little effect on CoA. Addition of CoA does not reverse inhibition. Benemid inhibits acid secretion, and its effect is additive with that of NEM and 2,4-dinitrophenol. The lipoic acid content as assayed by S. faecalis is unaffected by IAAm or arsenite and only by high concentration of NEM. The effect of arsenite is strongly additive with that of the other inhibitors. Diphenylchloroarsine inhibits and is not reversed by GSH. No certain conclusions concerning the relation of metabolism and function can be drawn from this work.