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Extrahepatic Cell Membrane Lipid Abnormalities and Cellular Dysfunction in Liver Disease

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Summary

Liver disease is associated with characteristic changes in the lipid composition of the surface coat of plasma lipoprotein particles. Cholesterol and lecithin molecules accumulate as hepatic secretion of lecithin-cholesterol acyltransferase decreases, and the arachidonate content, the precursor for eicosanoid production, is also reduced. By exchange and equilibration processes, such abnormal circulating lipoproteins should tend to induce corresponding changes in cell membrane lipid composition; studies in both human and experimental liver disease confirm that this does occur and that it is widespread. The correct functioning of membrane proteins, which serve as receptors or are responsible for enzymatic and transport processes, is most commonly dependent on the fluidity of their lipid bilayer matrix. Because cholesterol enrichment of biomembranes reduces bulk lipid fluidity, it can be predicted that extrahepatic membrane dysfunction might be a general feature of severe liver disease. This concept is supported by increasing experimental evidence and, as a consequence, it is proposed that many of the cellular disturbances and metabolic abnormalities accompanying hepatic disease result from, or are exacerbated by, lipoprotein-induced changes in membrane lipid composition and function. Importantly, this mechanism also suggests that drugs which can fluidise membranes, such as S-adenosyl-L-methionine (SAMe), might help ameliorate cellular dysfunction.

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  1. Academic Department of Medicine, Royal Free Hospital School of Medicine, London, UK

    James S. Owen

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Owen, J.S. Extrahepatic Cell Membrane Lipid Abnormalities and Cellular Dysfunction in Liver Disease. Drugs 40 (Suppl 3), 73–83 (1990). https://doi.org/10.2165/00003495-199000403-00008

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