By Andrew Golin,
The terms “good cholesterol” and “bad cholesterol” are used repeatedly to describe high-density lipoproteins (HDL) and low-density lipoproteins (LDL) respectively. But what are HDL or LDL? What actually is cholesterol and why do we need it? In order to understand what HDL and LDL are and why they are regarded as “good” and “bad” cholesterol, it is important to first understand cholesterol’s importance in our bodies. Simply put, cholesterol is a special type of fat molecule with a distinct structure. Its unique 3D conformation plays an important role in biological functions necessary for life.
As humans, we are composed of trillions of cells. Cells are the smallest structural and functional units of living organisms. An important structural feature of these units are cellular membranes, which encapsulate each and every cell. Membranes are sheet-like structures that act as a boundary between the inside of the cell and the outside environment. Membranes also act as a semi-permeable barrier to substances outside the cell. That is, membranes allow entry of certain components inside the cell yet excludes the entry of others. If the cell membrane of a cell were to break and could not reform, or if it allows the entry of unwanted substances, the cell would die. In order for the cell membrane to remain intact and to be permeable to certain molecules that the cell needs, the membrane requires cholesterol.
As water molecules accelerate when boiled, or as water freezes and packs together to form ice at freezing temperatures, the molecules which compose our membranes act similarly: the numerous components which makeup our cell membranes can move rapidly and pack tightly together depending on the temperature of the cell’s environment. Cholesterol is critical to our cells because of its structural inelasticity. In cellular membranes, cholesterol’s rigidity allows it to act as a buffer against extreme or non-ideal temperature conditions.
As seen above, cholesterol (hexagon structures) evidently has a different configuration than the phospholipid (circular structures), the chief component of cell membranes. The rings that make up cholesterol are inflexible and bulky relative to the chains extending from the phospholipids, thus requiring a greater amount of energy (and therefore heat) to cause cholesterol to move around the membrane. On the other end of the temperature spectrum, the cold causes our membranes to pack tightly stopping important molecules from entering. The chains extending from the phospholipid head groups can pack together tightly, whereas cholesterol’s bulky structure interrupts the tight packing confirmation that phospholipids are able to achieve. In summary, cholesterol acts as a fluidity buffer against non-ideal temperatures and allows our membranes to restore the ideal fluid composition.
Cholesterol is accumulated by two methods. Firstly, it can be obtained from diets containing animal products. Secondly, it can be synthesized from other starting molecules such as proteins or carbohydrates we obtain via our diets. Consequently, eliminating all fat from one’s diet alone will not definitely lower one’s cholesterol concentration, as fat can be synthesized from sugar or protein! Cholesterol regulation is therefore a matter of caloric intake versus caloric expenditure.
High-density lipoprotein and low-density lipoprotein particles contain proteins in addition to cholesterol. Lipoprotein molecules contain proteins called apolipoproteins. Apolipoproteins are very dense relative to the lipid components of these particles. Therefore, high-density lipoproteins contain a higher ratio of protein to lipid than low-density lipoprotein.
HDL and LDL are the two major forms of cholesterol in the body. The primary function of LDL particles is to transport cholesterol to peripheral tissues. LDL particles are able to pick up excess cholesterol in the blood and help deposit it into tissues. The opposing function of HDL particles is the reverse transport of cholesterol from peripheral tissues to the liver. The liver can then eliminate cholesterol by excreting it as bile salts, which act as molecular detergents used in the breakdown of fat products in the small intestine. Though both functions are critically important for the body’s biochemical needs, elevated amounts of LDL may lead to adverse events.
Excess LDL particles are harmful due to the correlation of LDL particles and atherosclerosis, an inflammatory condition where fatty plaques lining blood vessels can rupture causing clinical events1. Firstly, LDL is transported into arterial walls and is retained1. As cut apples develop a brown covering over time due to a process called oxidation, where electrons are lost from the apple, lipoproteins in arterial walls can be oxidized analogously1. Cells of the artery walls secrete molecules which act as oxidants1. These secreted oxidizers then remove electrons from LDL particles which aid in the plaque formation from LDL1. A high concentration of HDL is beneficial as it decreases the concentration of cholesterol from peripheral tissues, thereby reducing the amount of LDL oxidation that can occur1. It should also be noted that HDL may contain proteins which act as oxidizing blockers which further protect arteries from developing plaque lesions.1
As most people already know, diet and exercise should be the first method of action towards lowering LDL concentration levels. Diets containing unsaturated fats, whole-grains, high-fiber foods, and fish will help lower the prevalence of cardiovascular disease and lower LDL concentration2. Physical activity enhances skeletal muscle’s ability to use lipids as a fuel source over glycogen, the storage form of glucose. Lipids will therefore be broken down at an accelerated rate resulting in a decrease of lipid concentration in the plasma. This results in a decrease of excess cholesterol in the blood so fewer LDL particles are synthesized. Furthermore, the enzyme which synthesizes HDL particles using cholesterol as a substrate, lecithin-cholesterol acyl transferase (LCAT), has been seen to increase in activity following exercise3. Lastly, if diet and exercise together has proven to be ineffective against one’s lipid profile, statins are often effective against elevated LDL concentrations as statins inhibit the biosynthesis of cholesterol from cholesterol precursor molecules. By inhibiting cholesterol synthesis, the decrease of cholesterol concentration in the blood results in fewer LDL particles from forming3.
References:
- Berliner J, Navab M, Fogelman A et al. Atherosclerosis: Basic Mechanisms: Oxidation, Inflammation, and Genetics. Circulation. 1995;91(9):2488-2496. doi: 10.1161/01.cir.91.9.2488.
- Bruckert E, Rosenbaum D. Lowering LDL-cholesterol through diet: potential role in the statin era. Current Opinion in Lipidology. 2011;22(1):43-48. doi:10.1097/mol.0b013e328340b8e7.
- Cholesterol Molecules Part Of A Phospholipid Bilayer.; 2017. Available at: http://homepage.smc.edu/wissmann_paul/anatomy2textbook/1cholesterol.html. Accessed March 3, 2017.