Decreased thiosulfate sulfur transferase (rhodanese) in Leber's hereditary optic atrophy

Abstract

In mammals the major portion of cyanide is converted to thiocyanate by the liver enzyme thiosulfate sulfur transferase (TST) (rhodanese). We have found a much reduced activity of this enzyme in liver biopsies from two affected males of a family with Leber's hereditary optic atrophy and in two isolated cases of the same disease, (compared to liver biopsies from controls or liver samples obtained at autopsy). In one of the patients we studied the effect of a 3-day thiosulfate infusion. The urinary excretion of thiocyanate which was low prior to the infusion was raised during the thiosulfate treatment; in a healthy control person the same thiosulfate infusion did not alter the thiocyanate excretion rate. This suggests that cyanide detoxification which is suboptimal in patients with Leber's disease may be increased by thiosulfate infusion.

BAEP changes in Leber's hereditary optic atrophy: further confirmation of multisystem involvement

“…Some biochemical data suggests an inborn error of cyanide metabolism (23,24) concerning the mechanisms of cyanide detoxification. However, the study of the rhodanese enzyme, implied in this metabolic pathway, has not provided conclusive results (3,19,(16)(17)(18). The disease generally manifests acutely or sometimes subacutely with visual loss affecting often both eyes.…”

The Expression and Activity of Rhodanese, 3-Mercaptopyruvate Sulfurtransferase, Cystathionine γ-Lyase in the Most Frequently Chosen Cellular Research Models

“…Kruithof et al [ 43 ] showed that TST deficiency was strongly related to the pathophysiology of metabolic diseases, including diabetes and obesity. There is some evidence of STRs activity playing a role in several other diseases, such as Lebers Hereditary Optic Disease (LHOD) (TST) [ 44 , 45 ], human gliomas (TST, MPST, CTH) [ 46 ] and in hemodialysis patients (TST) [ 47 ]. Therefore, these enzymes provide challenges in several fields and responding to them could not only improve the understanding of various diseases but may also provide a way to treat them.…”

Rhodanese-Fold Containing Proteins in Humans: Not Just Key Players in Sulfur Trafficking

“…The study of liver biopsies of patients showed that TST activity decreases during the disease progression. Indeed, infusion of these patients with thiosulfate does not cause an increase in the urinary concentration of thiocyanate, in contrast to what is observed for healthy individuals [ 52 ]. This suggests that cyanide detoxification is suboptimal in patients with Leber’s disease, probably due to decreased TST activity.…”