Alterations of lipid synthesis in the normal and dysmyelinating trembler mouse sciatic nerve by heavy metals (Hg, Pb, Mn, Cu, Ni)

Lipid synthesis from 14C-labeled acetate was dramatically reduced by inorganic mercury in the mouse sciatic nerve in vitro (IC 50 was 10 μM). The dysmyelinating trembler mutant was less affected (IC 50 was 40 μM). Under the same conditions, lipid synthesis was less inhibited by inorganic lead but was increased 3 times by manganese, copper and nickel at < 2 MM. Although the syntheis of all lipids is dramatically reduced by inorganic mercury, their relative proportions vary in the presence of this metal:cholesterol synthesis was inhibited most strongly, phosphatidylcholine synthesis was also reduced, whereas synthesis of other lipids was relatively unchanged (phosphatidylserine, phosphatidyl inositol, sphingomyelin, cholesterol esters, cerebrosides). Incorporation of [ 14C]acetate into free fatty acids was enhanced by a factor of 4 in the presence of inorganic mercury.