Importance of the Disulfide (-S-S-) Linkage in the Blood-Clotting Mechanism

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Abstract
A variety of compounds capable of blocking the action of -SH groups and -S-S- linkages, respectively, were introduced into a 2-stage clotting system - the modified 2-stage method for the quantitative estimation of prothrombin. The inhibitory effect on clotting by certain of these compounds was measured as a change in thrombin yield. Also, by introducing these compounds into the clotting system at the various steps of the 2-stage procedure, it was possible to determine the site of action of these compounds in the molar concns. used. Two principal test systems were used: In the one, the molar concn. of the test reagent was held constant and the plasma was incubated with the reagent for a variable time; in the other, the plasma-reagent incubation time was held constant and the molar concn. of the test reagent was varied. The results showed that compounds which are commonly used to alter the disulfide linkage caused a pronounced inhibition of clotting by decreasing the reactivity of assayable prothrombin, whereas those that are used to alter sulfhydryl groups did not. The inhibitory effect on clotting caused by the disulfide blocking reagents could be reversed partially and occasionally completely by suitable oxidation or by dialysis.

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