New York: By mapping the structure of a key enzyme involved in cholesterol production, researchers have gained new insights into genetic disorders as well as the possibility of new approaches to lowering blood cholesterol when it becomes dangerously high.
The cholesterol-making process in cells requires about 30 chemical reactions and 20 enzymes, seven of which are embedded in the cellular membrane.
The mapping project focused on one of these, sterol reductase, which helps two electrons travel from a molecule known as NADPH to another molecule that will eventually become cholesterol. This type of reaction is known as a reduction.
"This is the first report to pinpoint the location of every atom - in this case nearly 3,000 of them - in one of the membrane-embedded enzyme cells use to make cholesterol," said co-researcher Ganter Blobel from the Rockefeller University in the US.
"With the structure of this enzyme, we can better understand how the body synthesizes it," Blobel added.
"Our images revealed two pockets within the enzyme's architecture. One contains the NADPH, and the other provides access to the cholesterol precursor. When in place, these molecules are close enough to spark this important step in the synthesis of cholesterol," first author, Xiaochun Li pointed out.
The research also has implications for treatment of high cholesterol, Blobel noted.
"Many of the pills currently available interfere with early steps in the complex series of reactions, which generate cholesterol. Our reaction occurs later, and may offer a new target worth investigating," Blobel added.
Cholesterol can become a hazard when travelling in the blood, leading to the formation of potentially blood-vessel blocking plaques.
The findings appeared in the journal Nature
