Wedeloside, a powerful inhibitor and ligand of the mitochondrial ADP/ATP carrier

Abstract

The effect of wedeloside, an atractyloside analogue occurring in the Australian weed Wedelia asperrima, on the ADP/ATP carrier is investigated on 3 levels; the ADP stimulated respiration, the ADP/ATP exchange, and the binding in competition with atractylate (ATR) and carboxyatractylate (CAT). The inhibition of respiration and of ADP/ATP exchange by wedeloside is nearly uncompetitive with ADP. The competitive binding with [ 3 H]cat and [ 3 H]ATR reveals a high binding affinity of wedeloside similar to that of CAT. The titration of the ADP/ATP exchange and of the binding with wedeloside gives a titer of 0.35 protein for rat liver protein and the titer of the binding gives 2.7 protein for beef heart mitochondria. The 1.8‐times higher titers than with CAT may indicate that two molecules of wedeloside bind to one ADP/ATP carrier dimer in contrast to the half site reactivity known for the binding of the other ligands.