INHIBITION OF NEUTRAL CHOLESTERYL ESTER HYDROLASE BY THE GLYCOLYTIC ENZYME ENOLASE - IS THIS A SECONDARY FUNCTION OF ENOLASE

There is an accumulation of the glycolytic enzyme enolase and of chole steryl esters in macrophages that have been converted into ''foam'' ce lls. In this study, we questioned whether enolase could be involved in this accumulation of cholesteryl esters by inhibiting the activity of neutral cholesteryl ester hydrolases. Enolase from both yeast and rab bit muscle were incubated with three different cholesteryl ester hydro lases and were shown to inhibit the hydrolysis of cholesteryl esters. Inhibition was dependent on the concentration of enolase and appeared to occur through binding of the enolase to the cholesteryt ester. Neve rtheless, the yeast and rabbit muscle enolases differed in their effic iency of inhibition and in their mechanism of action. Purification of commercial enolase preparations by gel-filtration yielded single prote ins with the same inhibitory activities as the originals, indicating t hat the inhibition was not due to the presence of an impurity. Partial ly purified alpha alpha- and gamma gamma-isoforms of the enzyme from r at brain also appear to have inhibitory effects on cholesteryl ester h ydrolysis. Negative control of the hydrolytic phase of the cholesterol /cholesteryl ester cycle may be a secondary function of enolases which correlates with the accumulation of cholesteryl esters in a number of neuro-degenerative and demyelinating diseases.