Effect of Copper on l-Cysteine/l-Cystine Influx in Normal Human Erythrocytes and Erythrocytes of Wilson’s Disease

Abstract

Wilson's disease is a disease of abnormal copper metabolism in which free serum copper level is raised. The objective of the study was to determine, whether in Wilson disease, L-cysteine/L-cystine influx into RBC was decreased or not and the specific amino acid transporter affected by copper in normal human RBC. For L-cysteine/L-cystine influx, ten untreated cases, ten treated cases and ten age and sex matched healthy controls were recruited. To study the effect of copper on L-cysteine/Lcystine influx in RBC, 15 healthy subjects were selected. RBC GSH and L-cysteine/L-cystine influx were estimated by Beautler's and Yildiz's method respectively. In untreated cases, L-cysteine/L-cystine influx and erythrocyte GSH level were decreased showing that elevated level of free copper in serum or media decreased L-cysteine/Lcystine influx in human RBC. Copper treatment inhibited L amino acid transporter in normal RBC specifically.

Metabolomics profiles of patients with Wilson disease reveal a distinct metabolic signature

“…Orally administered cysteine can also act as a copper chelator by forming a copper-cysteine complex, thereby inhibiting copper absorption in the gut (Baker and Czarnecki-Maulden, 1987). In untreated patients with WD, high plasma copper levels were shown to inhibit Lcysteine/L-cystine uptake in erythrocytes (Mandal et al, 2016) and GSH concentration was found to be reduced and significantly dependent on the L-cysteine/L-cystine uptake. Excess copper, then, can reduce cysteine bioavailability which may lead to increased cysteine demand (Robbins and Baker, 1980).…”