Sulfur Metabolism in AIDS: Cystamine as an Anti-HIV Agent

Numerous reports have documented disturbances of sulfur metabolism in AIDS patients. There is a generalized loss of sulfur from the body, measured as cysteine and glutathione. The enzyme, cystathionase, has been shown to be greatly decreased in the liver of AIDS patients. Cystathionase is known to catalyze beta elimination of cystine giving rise to sulfane sulphur, which has potent stimulatory properties for lymphocytes. When both cystine and cystathionase are deficient in AIDS, the lymphocytes would lack this important regulator, which might be replenished by giving cystamine. Cystamine is a small disulfide that gives rise to sulfane sulfur when it undergoes oxidation catalyzed by diamine oxidase (a ubiquitous enzyme in animals). Cystamine has been shown to cause marked suppression of HIV replication in cultured lymphocytes and macrophages; the inference is that the cystamine/diamine oxidase system may replace the cystine/cystathionase system as a source of sulfane sulfur. Sulfane sulfur could have two beneficial effects: (1) it could increase the vigor and resistance of the lymphocyes and (2) it could interfere with the HIV replication process. A clinical trial of cystamine in AIDS is indicated.