Gymnemic acid II inhibits heme binding to glyceraldehyde-3-phosphate dehydrogenase

Gymnemic acid (GA) is a saponin of triterpene glycoside isolated from the plant Gymnema sylvestre.GA is not a pure entity but is comprised of several types of homologs.GA suppresses taste sensitivity to sweetness and inhibits intestinal glucose absorption.We previously found that GA inhibits rabbit glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity.GAPDH is a key enzyme in glycolysis, and binds with heme.We now found that purified GA II inhibited heme-binding to murine GAPDH.Heme binding did not affect the GA II binding to GAPDH.The inhibition of heme-binding to GAPDH was not observed with the aglycone part, gymnemagenin and was reduced by deacylation of GA II.Thus, the acetyl and/or 2methylbutyroyl moieties and glycone glucuronic acid of GA II were necessary for the inhibitory effect of GA II on the formation of the GAPDH-heme complex.