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The effects of sterol structure upon sterol esterification
Don S Lin1, Robert D Steiner, Louise S Merkens
1Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine, Oregon Health & Science University, Portland, Oregon, USA.
Atherosclerosis
|August 15, 2009
Summary
Sterol structure significantly impacts esterification by lecithin cholesterol acyltransferase (LCAT) and acyl-CoA cholesterol acyltransferases (ACAT). Different sterols and functional groups alter esterification rates by these key enzymes.
Area of Science:
- Biochemistry
- Lipid Metabolism
- Enzymology
Background:
- Cholesterol esterification is crucial for lipid transport and storage in mammals.
- Two main enzyme families, LCAT (lecithin cholesterol acyltransferase) in plasma and ACAT (acyl-CoA cholesterol acyltransferases) in tissues, mediate this process.
- The influence of sterol structure on esterification efficiency by these enzymes is not fully understood.
Purpose of the Study:
- To investigate the hypothesis that sterol structure significantly affects esterification by LCAT and ACAT.
- To analyze the esterification patterns of various non-cholesterol sterols in plasma and tissues.
- To quantify the impact of specific structural modifications on sterol esterification.
Main Methods:
- Analysis of sterol esters in plasma and tissues from patients with inherited sterol metabolism disorders (sitosterolemia and Smith-Lemli-Opitz syndrome).
- Measurement of sterol ester percentage of total sterols to define esterification levels.
- Comparative analysis of esterification rates for nine different sterols by LCAT and ACAT, including cholesterol and its analogs.
Main Results:
- LCAT and ACAT exhibit differential substrate specificity, with varying esterification efficiencies for different sterols.
- Specific structural features, such as A-ring saturation and side-chain modifications (e.g., C-24 methyl group), significantly altered esterification rates.
- LCAT preferentially esterified cholesterol (1.00), while ACAT showed higher esterification for cholestanol (1.29) and campestanol (1.21).
- Linoleic acid was the predominant fatty acid esterified by LCAT, whereas oleic acid was favored by ACAT.
Conclusions:
- Sterol structure is a critical determinant of esterification by both LCAT and ACAT.
- Understanding these structure-activity relationships provides insights into lipid metabolism and potential therapeutic targets.
- The findings support the hypothesis that enzyme-mediated sterol esterification is highly dependent on the sterol substrate's chemical structure.
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