Lecithin:cholesterol acyltransferase lipoprotein abnormalities

The liver is responsible for synthesis of cholesterol, high-density lipoproteins, and very-low-density lipoproteins. The enzymes lipoprotein lipase and lecithin-cholesterol acyltransferase also are synthesized in this organ. Increased serum triglyceride and FFA concentrations are encountered in patients with hepatic failure, primarily due to the increased lipolysis. The significant insulin resistance that can be seen in cirrhosis causes a shift to lipids as a fuel source. Whereas only 35% of total calories are derived from fat in normal patients after an overnight fast, this can increase to 75% in patients with cirrhosis. Incorporation of late evening snacks in patients with liver cirrhosis may correct abnormal substrate metabolism, increase carbohydrate, and decrease fat oxidation rates. ... 

A complete absence of LDL in the plasma is seen in patients with the rare autosomal recessive disorder, abetalipoproteinaemia. The patients may also have associated lecithin cholesterol acyltransferase deficiency which is also encountered as an independent conditon. In this latter case lipoproteins with abnormal flotation, size and compositional properties exist, with disc-shaped structures (nascent HDL particles ) being present at high concentration. 

The detection of abnormal lipoproteins can be done more effectively from the elution patterns monitored by protein or choline-containing phospholipids for the isolated lipoprotein fraction by the ultracentrifugation. In Fig. 20, the elution patterns of choline-containing phospholipids for each ultracentrifugal fraction are presented for three subjects normal female and patients with acute hepatitis and lecithin cholesterol acyltransferase deficiency. In contrast to normal subjects, all lipoprotein fractions for two pathological cases show the existence of abnormal lipoproteins in which a correlation between the particle size and density dose not exist. 

According to the above developed scheme of HDL and LDL structure, the molecular structure of cholesteryl esters is an important determinant to the size and internal arrangement of lipoproteins. This is further demonstrated by the structures of lipoprotein particles which lack cholesteryl esters. A natural system, where this is the case, is given by the abnormal lipoprotein Lp-X oc-curing abundantly in the serum of patients suffering from obstructive jaundice or from a familial deficiency in the enzyme lecithin-cholesterol-acyltransferase, which controls the conversion of cho-... 

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