bio6: Lipoproteins and Cholesterol (v1.0)

Cholesterol is a lipid and is a percussor to other important molecules like steroid hormones (see essay on hormones) and bile acids (important for digestion) and also creation of membranes. It is often thought of as the wicked witch of the west since it is equated to blood vessel blockages, but this reputation is really not wholly justified.

The amount of cholesterol you have depends on many factors, including genetics, diet, age, activity, and other elements. Cholesterol moves around in lipoprotein complexes. A good deal of the cholesterol actually is manufactured by the body and does not come from the diet. Most of the cholesterol in the body is manufactured in the liver. So, cholesterol synthesis (a long and complex 28 step process that I won't go into) in the body is a very important subject and influencing this process is the key to controlling the level of cholesterol in the body.  Many cholesterol reduction medicines like statins target the key enzyme (HMG-CoA Reductase) that facilities the process. 

The single most important role of cholesterol is creation of membranes (cellular, nuclear and mitochondria). Membranes are made of hydrophobic fatty acids/lipids (provides boundaries) and proteins (acts as gatekeepers to transport material in and out) and the cholesterol in the spaces in between makes it stiffer and this is critical for proper membrane function - to maintain integrity and help regulate the orderly movement of materials. 

Lipoprotein complexes transport cholesterol and fats. Lipoprotein complexes made in intestinal cells are ultra-low-density lipoproteins called ULDL's (or chylomicron), and like other lipoproteins, is water soluble (lipids by themselves are not). ULDLs are one of the five major groups of lipoproteins (sorted by density) that enable fats and cholesterol to move within the water-based solution of the bloodstream. Enzymes in the blood stream digest the fat in the ULDL's to release fatty acids and other molecules and these released molecules are ready to be absorbed by cells. The Chylomicron remnant as a result reduces in size and can then even transport through the capillaries. Chylomicron transported to the liver is absorbed, and contents stashed away.  The liver is the lipid regulator in the body, and it needs to package up its stored lipids and cholesterol as needed by the body too. The lipoproteins created by the liver to transport it out are VLDL (very low-density lipoproteins). When the fat in the VLDL is digested by blood enzymes, the remnant lipoprotein evolves to IDL and eventually LDL (low density lipoprotein - the infamous "bad cholesterol"). 

LDL contains the very highest concentration of cholesterol of all the lipoprotein complexes. LDL is the key vehicle to deliver cholesterol directly to cells that need it. The liver keeps tab on the LDL level in the blood stream. When cells demand a lot of cholesterol, the LDL level in the blood drops, and the liver ups VLDL production. High dietary saturated or trans-fat intake can inhibit the liver's ability to buffer dietary fats and cholesterol and can increase LDL level. Exercise also helps to lower LDL. Genetics can also distort receptors in cells for LDL that can result in a higher LDL in the bloodstream (Hypercholesterolemia).  

The problem with LDL though is not the cholesterol itself but the amount of unsaturated fatty acids they also contain. Unsaturated fatty acids are susceptible to oxidation, and this is the first step in atherosclerotic plaque formation. Plaque can block blood vessels. Plaque can also rupture and create clotting. The more the LDL, the more likely are the damaging reactions with the unsaturated fatty acids they contain and more the plaque. 

Does that mean you should avoid all unsaturated fats in your diet? No!! studies show that could be even worse. Unsaturated fats in diet have actually been found to reduce heart disease by reducing cholesterol while saturated and trans fats do the opposite. 

A word on HDL (high density lipoprotein). HDL is the so-called "good cholesterol". More HDL decreases atherosclerotic plaque. removes cholesterol and the absorbed cholesterol is returned back to organs, inhibits oxidation, inhibits inflammation, inhibits blood coagulation, and inhibits blood platelet aggregation. HDL increases with exercise, weight loss, consuming Omega-3, increased fiber in diet, reduce carbohydrates, and reducing trans fats from diet. 

Gallstones are painful. Gallstones are mostly cholesterol. Where there are bile acids there is cholesterol. If cholesterol to bile acid ratio gets too high, crystals of cholesterol form with painful results. Diverse bile acids are synthesized in the liver.