Dominant cholesterol-metabolism ideas challenged by ne...( A team of researchers investigating c...)

A team of researchers investigating cholesterol and lipid transport has performed experiments that cast serious doubt on the dominant hypothesis of how the body rids its cells of "bad" cholesterol (LDL) and increases "good" cholesterol (HDL). Cholesterol metabolism is an area of intense inquiry because high levels of LDL cholesterol or total cholesterol put about half of all Americans at significant risk of heart disease.

The team was led by Robert A. Schlegel, Professor of Biochemistry and Molecular Biology at Penn State University, and Patrick Williamson, the Edward S. Harkness Professor of Biology at Amherst College. The paper by Schlegel, Williamson, and their colleagues will be published on Wednesday, 15 August 2007, in the on-line journal PLoS One.

A protein called ABCA1 is critical for producing "good" cholesterol: patients who lack the gene for this protein produce no HDL, and as a result, suffer from heart attacks at an early age. An important question is what ABCA1 does that is so important for producing HDL.

The most popular hypothesis was put forth in 2000 by Giovanna Chimini, Group Leader of a laboratory in the Centre d'Immunologie Marseille-Luminy in France, and colleagues. They suggested that the ABCA1 enzyme plays a major role in the transfer of a phospholipid called phosphatidylserine (PS) from the inside of the cell -- where it is normally concentrated -- across the cell membrane to the outer surface of the cell. This is a crucial first step in the mechanism by which excess lipids and cholesterol are eliminated from the body. Under normal conditions, there is a second important step. After the PS is expressed on the cell surface, the phospholipids and excess cholesterol can be loaded onto a circulating protein, apoA1, to generate an HDL cholesterol particle. HDL cholesterol carries the lipids through the blood stream to the liver, where they are dumped into the in
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