Alterations in erythrocyte membrane lipid and its fragility in a patient with familial lecithin:cholesterol acyltrasferase (LCAT) deficiency.
Lecithin:cholesterol acyltrasferase (LCAT) plays a key role in the cholesterol metabolism-mediated esterification of free cholesterol into the cholesterol ester in normal plasma. Familial LCAT deficiency is frequently associated with anemia. Using biochemical and physiological techniques, the erythrocytes of this patient were investigated to gain an insight into the relationship between the abnormalities of lipid metabolism and erythrocyte membrane fragility. Abnormal erythrocytes, so-called Target cells and/or Knizocytes, were observed at 20% in our patient's erythrocytes. Moreover, the mean corpuscular volume of the patient's cells was 7% greater than that of a normal individual. In the membrane lipids of the patient's erythrocytes, cholesterol and phosphatidylcholine increased, and phosphatidylethanolamine decreased. The electron spin resonance technique with a fatty acid spin probe showed that the membrane fluidity was more elevated than that of normal cells in spite of the increase in cholesterol content and the cholesterol/phospholipid ratio of the membrane of patient's erythrocytes. The patient's abnormally shaped erythrocytes were less deformed than those of the normal individual under high shear stress. The partial depletion of membrane cholesterol from the patient's erythrocytes was demonstrated by incubation with normal plasma with LCAT activity. The increment of transformed erythrocytes during the incubation could be prevented by cholesterol depletion from the patient's erythrocyte membrane. These findings indicate that normochromic anemia of the patient might be caused by erythrocyte fragility resulting from decreased deformity and/or abnormal shape of the cells due to abnormal lipid composition in the membrane.
D000328:Adult; D002784:Cholesterol / Q000097:blood; D003241:Consanguinity; D004907:Erythrocyte Deformability / Q000187:drug effects; D004909:Erythrocyte Indices; D004910:Erythrocyte Membrane / Q000737:chemistry* / Q000187:drug effects; D004913:Erythrocytes, Abnormal / Q000737:chemistry* / Q000187:drug effects; D005260:Female; D006801:Humans; D007863:Lecithin Cholesterol Acyltransferase Deficiency / Q000097:blood* / Q000235:genetics; D008560:Membrane Fluidity / Q000187:drug effects; D008563:Membrane Lipids / Q000097:blood*; D009996:Osmotic Fragility / Q000187:drug effects; D010375:Pedigree; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D010713:Phosphatidylcholines / Q000097:blood; D010714:Phosphatidylethanolamines / Q000097:blood
D008563:Membrane Lipids; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D002784:Cholesterol; D007862:Phosphatidylcholine-Sterol O-Acyltransferase