Endogenous generation of cyanide in neuronal tissue: Involvement of a peroxidase system

In a study of the mechanism by which cyanide is produced in neural tissue, it was hypothesized that nerve cells generate cyanide in a manner similar t o that in leukocytes. As in white blood cells, glycine addition enhanced cy anide production in rat pheochromocytoma cells. Because myeloperoxidase cat alyses cyanide production in leukocytes, a selective myeloperoxidase inhibi tor (aminobenzoic acid hydrazide) was tested and found to inhibit opiate ag onist-induced cyanide production in pheochromocytoma cells and also in rat brain. In addition, hydrogen peroxide enhanced cyanide release in pheochrom ocytoma cells, further suggesting that the process is oxidative in nature. Sonicated rat pheochromocytoma cells did not generate cyanide in response t o an agonist acting on surface receptors even though disrupted cells respon ded to glycine. The mitochondrial fraction from rat brain produced more cya nide in response to glycine than any other fraction. Thus glycine seems to act at an intracellular site to enhance cyanide production and the process seems to involve a peroxidase mechanism similar to that reported for white blood cells. (C) 2000 Wiley-Liss, Inc.