Journal of Lipid Research, Vol 38, 585-591, Copyright © 1997 by Lipid Research, Inc.

ARTICLES

Catalytically inactive lecithin: cholesterol acyltransferase (LCAT) caused by a Gly 30 to Ser mutation in a family with LCAT deficiency

XP Yang, A Inazu, A Honjo, I Koizumi, K Kajinami, J Koizumi, SM Marcovina, JJ Albers and H Mabuchi
Second Department of Internal Medicine, School of Medicine, Kanazawa University, Ishikawa, Japan.

Plasma lecithin:cholesterol acyltransferase (LCAT) plays an important role in early steps of reverse cholesterol transport, i.e., cholesterol efflux from peripheral tissues and cholesterol esterification in HDL. However, structural and functional relationships of LCAT have not been fully elucidated. We described a missense mutation of Gly 30-to-Ser in a patient with classical LCAT deficiency. The proband was homozygous for the mutation and had a very low level of HDL cholesterol (2 mg/dl), with a half of normal LCAT mass (2.75 micrograms/ml), but no detectable or very low LCAT activity in endogenous and exogenous substrate assays. Both his mother and sister were heterozygous for the mutation, and had slightly decreased levels of HDL cholesterol (34 and 36 mg/dl, respectively). Transient expression study using COS cells indicated that mutant cDNA produces similar amounts of media protein as compared to wild type, but no detectable LCAT activity. The missense mutation may result in a near-native conformation without large effects on cellular secretion but a catalytically defective protein. Thus, the N- terminal domain appears crucial for enzymatic activity, in addition to the catalytically active consensus sequence of Gly179 to Gly183 and a putative sterol binding domain of Glu154 to Lys173.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				F. Peelman, J-L. Verschelde, B. Vanloo, C. Ampe, C. Labeur, J. Tavernier, J. Vandekerckhove, and M. Rosseneu Effects of natural mutations in lecithin:cholesterol acyltransferase on the enzyme structure and activity J. Lipid Res., January 1, 1999; 40(1): 59 - 69. [Abstract] [Full Text]

				G. Argyropoulos, A. Jenkins, R. L. Klein, T. Lyons, B. Wagenhorst, J. St. Armand, S. M. Marcovina, J. J. Albers, P. H. Pritchard, and W. T. Garvey Transmission of two novel mutations in a pedigree with familial lecithin:cholesterol acyltransferase deficiency: structure–function relationships and studies in a compound heterozygous proband J. Lipid Res., September 1, 1998; 39(9): 1870 - 1876. [Abstract] [Full Text]

				G. Lambert, N. Sakai, B. L. Vaisman, E. B. Neufeld, B. Marteyn, C.-C. Chan, B. Paigen, E. Lupia, A. Thomas, L. J. Striker, et al. Analysis of Glomerulosclerosis and Atherosclerosis in Lecithin Cholesterol Acyltransferase-deficient Mice J. Biol. Chem., April 27, 2001; 276(18): 15090 - 15098. [Abstract] [Full Text] [PDF]