Structure Of HDL Cholesterol Determined

May 24, 1999

Using novel methods for performing infrared spectroscopy recently developed in his laboratory, assistant professor of pharmacology Paul H. Axelsen, MD, and his colleagues have resolved a contentious scientific debate over the structure of high-density lipoproteins, or HDL particles, the so-called "good" cholesterol.

The team's findings are reported in the May 21 issue of the Journal of Biological Chemistry. HDL is thought to be responsible for ferrying cholesterol from various body tissues to the liver for reprocessing or elimination. In this way, HDL particles are thought to play a crucial role in reducing the risk of atherosclerotic cardiovascular disease. Prior to this study, many scientists thought HDL particles consisted of two-layered disks of fatty molecules, or lipids, surrounded by a "picket fence" of proteins at the disk's edge. A smaller number of investigators also believed that the lipid molecules comprised a two-layered disk, but that the proteins surrounding the disk were wrapped around the disk's perimeter in a "belt" formation. Existing tools for determining molecular structure were technically limited, leaving advocates for the competing models of HDL's structure at odds and without means to resolve the controversy. The best known tool for determining molecular structure,

X-ray crystallography, could not be employed because no one knows how to form HDL particles into the requisite crystals. NMR and older forms of infrared spectroscopy both require samples to be dried at one point in their preparation.

However, lipoprotein structures are disrupted in the drying process, because they are held together by their mutual repulsion from water, a phenomenon known as the hydrophobic effect. The novel infrared spectroscopy methodology developed by Axelsen and his coworkers enabled them to study HDL particles in water and in their native state. Their results verify the lipid bilayer structure in the particles, presumed in both the "picket fence" and "belt" models, and point unambiguously to the belt model for the orientation of the surrounding proteins.

"These findings turn our understanding of HDL structure, not on its head but on its side," Axelsen says. "It's now clear that the proteins in HDL are rotated 90 degrees from what had been the prevailing view."
-end-


University of Pennsylvania School of Medicine

Related Cholesterol Articles from Brightsurf:

Cholesterol's effects on cellular membranes
The findings have far-reaching implications in the general understanding of disease, the design of drug delivery methods, and many other biological applications that require specific assumptions about the role of cholesterol in cell membranes.

Autism-cholesterol link
Study identifies genetic link between cholesterol alterations and autism.

Microbes might manage your cholesterol
Researchers discover a link between human blood cholesterol levels and a gene in the microbiome that could one day help people manage their cholesterol through diet, probiotics, or entirely new types of treatment.

Experimental cholesterol-lowering drug effective at lowering bad cholesterol, study shows
Twice-yearly injections of an experimental cholesterol-lowering drug, inclisiran, were effective at reducing low-density lipoprotein (LDL) cholesterol, often called bad cholesterol, in patients already taking the maximum dose of statin drugs, according to data of the ORION-10 trial presented Saturday, Nov.

Rethinking how cholesterol is integrated into cells
Cholesterol is best known in connection with cardiovascular disease, but cholesterol is also vital for many fundamental processes in the body.

Seed oils are best for LDL cholesterol
Using a statistical technique called network meta-analysis, researchers have combined the results of dozens of studies of dietary oils to identify those with the best effect on patients' LDL cholesterol and other blood lipids.

Cholesterol leash: Key tethering protein found to transport cellular cholesterol
Cholesterol is an essential component of living organisms, but the mechanisms that transport cholesterol inside the cell are poorly understood.

New way to treat cholesterol may be on the horizon
A breakthrough discovery by scientists at Houston Methodist Research Institute could change the way we treat cholesterol.

How low should LDL cholesterol go?
New analysis shows that in a high-risk population, achieving ultra-low LDL cholesterol levels, down to <10 mg/dL, safely results in additional lowering of risk of cardiovascular events.

Does boosting 'good' cholesterol really improve your health?
A new review addresses the mysteries behind 'good' HDL cholesterol and why boosting its levels does not necessarily provide protection from cardiovascular risk for patients.

Read More: Cholesterol News and Cholesterol Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.