Question

In their acceptance speech for the Nobel Prize in 1985, Michael Brown and Joseph Goldstein said, “Cholesterol is a Janus-faced molecule. The very property that makes it useful in cell membranes, namely its absolute insolubility in water, also makes it lethal.” Can you explain this remark?

Answer 1

Triacylglycerols, phospholipids, cholesterol,and cholesterol esters are transported in plasma with proteins, lipoproteins. These lipid-protein complex function as a lipid transport system as lipid is insoluble in blood. There are four types of lipoproteins in blood - Chylomicrons, Very low density lipoproteins (VLDL), low density lipoproteins (LDL), and high density lipoproteins (HDL)

Chylomicrons and VLDL deliver TAG to cells in the body. Chylomicrons are synthesised in the enterocytes and VLDL in the liver.

As VLDL particles get devoid of triacylglycerol, are transformed into LDL in the liver. The function of LDL is to deliver cholesterol to cells, where it is used in membranes, or for the synthesis of steroid hormones. Cells take up cholesterol by receptor-mediated endocytosis.

HDL absorbs cholesterol and carries it back to the liver. The liver then flushes it from the circulation by receptor-mediated endocytosis. HDL is synthesized and secreted by the liver and small intestine. It travels in the circulation where it gathers cholesterol to form mature HDL, which then returns the cholesterol to the liver.

HDL are good cholesterol while LDL are bad cholesterol. Storage of cholesterol in the wall of arteries,termed atherosclerosis, causes coronary heart disease and stroke by blocking the flow of blood to heart muscle or brain. Artherosclerosis is the hardening and narrowing of the arteries that blocks arteries inhibiting the blood flow resulting in  heart attacks, strokes, and peripheral vascular disease termed as cardiovascular disease.