The Role of Lecithin:Cholesterol Acyltransferase Deficiency in the Apoprotein Metabolism of Alcoholic Hepatitis

Abstract

In alcoholic hepatitis a severe but reversible LCAT deficiency provides a model to investigate the role of LCAT in lipoprotein metabolism. Serial changes in the lipid and apoprotein composition of the plasma lipoproteins were investigated throughout the illness of patients with alcoholic hepatitis. In severe alcoholic hepatitis, LCAT and cholesteryl esters were greatly reduced or undetectable in plasma. Lipoproteins were isolated by sequential ultracentrifugation of fasting plasma. VLDL was normal in triglyceride and phospholipid content but deficient in cholesteryl esters. Polyacrylamide gel electrophoresis of this fraction revealed greatly increased apo B (≈97%) as tetra-methylurea insoluble protein with traces of apo C and apo E, a composition compatible with nascent VLDL of hepatic origin. LDL was rich in triglyceride but deficient in cholesteryl esters. HDL was enriched in phospholipid but deficient in cholesteryl esters. Polyacrylamide gel electrophoresis demonstrated only apo B in LDL. The predominant lipoprotein in HDL was apo E (≈40%)and apo AI was deficient. By electron microscopy this fraction always contained some 150-240 A bilamellar discs, and in severe alcoholic hepatitis normal spherical HDL were rarely seen. This fraction appears to represent nascent HDL. During recovery LCAT activity and lipoprotein composition gradually normalized. Apo B in VLDL decreased with concomitant increases in apo E and apo C. In HDL, apo E decreased as apo AI increased. These results suggest that in the absence of LCAT nascent VLDL and nascent HDL accumulate in plasma, indicating that LCAT is required for the metabolism of these lipoproteins. A complex of LCAT and apo AI may act on nascent HDL, leading to the transfer of apo E, apo C., and cholesteryl esters to the nascent VLDL → LDL pathway. Apo E, the principal apoprotein of nascent HDL, is probably a major secretory apoprotein which plays a central role in cholesterol transport between lipoprotein classes.

Key Words:

• cholesterol
• cholesteryl esters
• electron microscopy
• high density lipoproteins (HDL)
• lipoproteins
• low density lipoproteins (LDL)
• liver
• phospholipid
• triglyceride
• very low density lipoproteins (VLDL)