Urea, Urease, Cyanate, and the Sickling of Hemoglobin S.
ARMY MEDICAL RESEARCH LAB FORT KNOX KY
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The hypothesis suggested recently that urea in sugar solutions interferes with the sickling event by ionization to cyanate and subsequent carbamylation of the hemoglobin S molecule was tested. Controlled studies in oxygen-free atmospheres have shown that SS cells, protected from sickling by urea-sugar solutions at clinically effective concentrations, were sickled subsequent to the addition of urease. The urea molecule per se interferes with sickling cyanate has no role in this action of urea. UREA 1 blocks and reverses sickling 2 protected sickle cells become sickled when incubated with urease 3 effects are reversible 4 effects are immediate and 5 effects are apparent in the deoxygenated state. CYANATE 1 blocks but does NOT reverse sickling 2 treated cells are unaffected by urease 3 effects are permanent 4 effects require time and 5 initially hemoglobin S must be oxygenated before carbamylation will occur. Thus, it is apparent that urea and cyanate interfere with sickling by distinctly separate molecular mechanisms. The blocking and desickling action of urea is urea-dependent. Possible molecular mechanisms for the action of urea are discussed. Author
- Medicine and Medical Research