Cysteine-S-Sulfate: Brain Damaging Metabolite in Sulfite Oxidase Deficiency1

Abstract

Cysteine-S-sulfate is an abnormal metabolite discovered in the urine and blood of a patient with cysteine oxidase deficiency, a rare disorder of sulfur amino acid metabolism associated with brain damage and mental retardation. The molecular structure of cysteine-S-sulfate closely resembles that of glutamate and related acidic amino acids which have both neuroexcitatory and neurotoxic properties (excitotoxic amino acids). Here we demonstrate that cysteine-S-sulfate induces the glutamate type of neuropathology in the rat central nervous system when administered subcutaneously to infants or intracerebrally to adults. It is postulated that cysteine-S-sulfate may be the neurotoxic agent responsible for brain damage in sulfite oxidase deficiency. The possibility that other excitotoxic amino acids could play occult roles in other unexplained neuropathologic conditions is discussed.