Urea, urease, cyanate, and the sickling of hemoglobin S.

Urea inglucose solutions has been advanced as a chemotherapeutic agent in sickle cell disease because it has been found effective both in reversing and in blocking sickling. It has been suggested recently that this beneficial action of urea may be the result of formation of cyanate from urea and subsequent carbamylation of beta S globin chains in the hemoglobin S molecule. In this paper, we show thatthe urea molecule per se interfereswith sickling. SS cellsinoxygen-free atmosphere, protected from sickling by ureasugar solutions,were sickled after urease was added. Urea blocks and reverses sickling;ureaprotected sickle cells become sickled after incubation with urease; these effects are reversible and immediate, and are apparent in the deoxygenated state. In contrast, cyanate blocks but does not reverse sickling;cyanate-treated cells are unaffected by urease; these effects are permanent and requiretime; and hemoglobin S must firstbe oxygenated before carbamylation willoccur. Evi. dently, urea and cyanate interferewith sickling by distinctlyseparate molecular mechanisms. Possible mechanisms for the action of urea are discussed.