Sunday, August 26, 2012

Cholesterol

Functions of Cholesterol

Cholesterol has several essential functions in the body: 

  • It is required for cell membranes to maintain membrane integrating and regulate fluidity
  • It is used to make myelin, which enables the electrical signals (action potentials) in neurons to move faster
  • It is used to make bile to digest lipids (fats, fat-soluble vitamins, etc)
  • It is used to make steroid hormones such as aldosterone (salt and water balance), vitamin D, corticosteroids (cortisol) and the sex hormones (testosterone, dihydrotesterone, estrogen and progesterone)  (see here)

This is why not having enough cholesterol can be a problem, as seen in Smith-Lemli-Opitz syndrome, a genetic disorder of impaired cholesterol synthesis, resulting in malformations, intellectual disability and other problems.

* Other living organisms use sterols.  Plants use phytosterols (stigmasterol, campesterol, beta-sitosterol) and fungi use ergosterols.

Where Cholesterol Comes From

Our body synthesises about 1,000 mg of cholesterol through a series of biochemical steps (see here) that ultimately converts 2 acetate molecules (carried by Acetyl CoA) to cholesterol.  Acetate can come from any macronutrient when they undergo aerobic metabolism to be burned for energy*.

Most of the cholesterol in our bloodstream is synthesised, but we can also get some from dietary sources.  Cholesterol levels and synthesis is regulated, when we absorb cholesterol from foods our body simply downregulates cholesterol synthesis.  Even the Australian dietary guidelines mention this**.  

“Eating cholesterol does not necessarily increase cholesterol in human blood plasma because when it is absorbed the liver tends to reduce its own endogenous cholesterol synthesis. About half the body’s cholesterol is made in the body from acetate.”  


* The standard cholesterol-lowering drugs are called 'statins', which are HMG-CoA reductase inhibitors.  HMG-CoA reductase is an enzyme that catalyses the third step of cholesterol synthesis.  Statins also inhibit the synthesis of other molecules in the cholesterol synthesis pathway, such as coenzyme Q10, squalene, isoprene and rho activation, which may be responsible for some of the adverse side-effects of statins 

** Let’s say an average person has a total cholesterol of 200 mg/dl and 5.0 litres of blood, so they have 10 grams of cholesterol in the bloodstream.  It’s easy to see how most people’s serum cholesterol is relatively unaffected when eating 300-400 mg of cholesterol (the Australian average), in other words 3-4% of their blood levels. 

Lipoproteins Transport Cholesterol

Cholesterol is fat-soluble and therefore has difficulty travelling throughout the bloodstream, which is mostly water.  The solution to this problem is to have a protein transporter (protein is water soluble).  High density lipoproteins (HDL), low density lipoproteins (LDL), intermediate density lipoproteins (IDL), very low density lipoproteins (VLDL) and chylomicrons transport cholesterol and other lipids (fatty acids, triglycerides, fat soluble vitamins) throughout the body (chylomicrons transport recently digested lipids from the small intestine)*.


HDL is often referred to as ‘good’ cholesterol and LDL as ‘bad’ cholesterol.  But HDL and LDL aren’t different types of cholesterol, rather they are different types of lipoproteins.  There is only one kind of cholesterol, C27H46O.  The reason why HDL is considered good cholesterol and LDL as bad cholesterol is because the amount of cholesterol in HDL particles (HDL-C) is negatively associated with cardiovascular disease and the amount of cholesterol in LDL particles (LDL-C) is positively associated with cardiovascular disease.  But it is quite simplistic to think of HDL as good and LDL as bad.  LDL carries out important functions such as distributing cholesterol, triglycerides and fat soluble nutrients.

* Other fat soluble things in the body have protein transporters.  For example the sex hormones are transported by sex hormone binding globulin (SHBG) 

** Sometimes people say ‘cholesterol is a fat’, which is wrong.  Cholesterol is a type of lipid.  Fatty acids, triglycerides, fat soluble vitamins and phospholipids are lipids as well.  Cholesterol is not a fat and looks nothing like one (see here) 

Further Reading:
(1) The straight dope on cholesterol – Part I
(2) The straight dope on cholesterol – Part II
(3) Cholesterol and Health — Functions and Foods
(4) The Full Story: Why Eggs Do Not Cause Cardiovascular Disease

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