Cholesterol in the human body is a term that is intimidating in itself. People suffering from high cholesterol are always curious to know all about it. So, what exactly is this cholesterol?

Where Does Cholesterol Synthesis Occur? 

Well, cholesterol is a waxy substance produced in the liver. It helps the body build cells, make cell membranes, produce hormones, and vitamin D. There are two sources of cholesterol in the blood.

One is the food that one consumes, and the other is the liver of the person. Consuming more than required fatty foods and oils and oil can make the liver produce extra cholesterol.

Where Does Cholesterol Synthesis Occur?

About cholesterol synthesis 

Biosynthesis of cholesterol usually takes place in the endoplasmic reticulum of the hepatic cell and begins with acetyl CoA. This acetyl CoA is derived from an oxidation reaction that happens in the mitochondria. However, acetyl CoA is also derivable from ethanol’s cytoplasmic oxidation by acetyl CoA synthetase.

De novo synthesis of cholesterol

Human beings or mammals can absorb cholesterol directly from dietary sources or can be synthesized de novo. Up to 70% – 80% of the cholesterol in the human body is synthesized de novo by the liver, and 10% of the cholesterol is synthesized de novo by the small intestine.

Main sites and organelles responsible for cholesterol synthesis

The liver and the intestinal mucosa are the two chief centers in the body where cholesterol synthesis takes place. The liver is the principal place for triacylglycerol and cholesterol synthesis. Suppose the triacylglycerol and cholesterol are more in the liver than its actual requirement. In that case, they are exported into the bloodstream in the form of lipoproteins of very low density (d<1.006 g cm-3).

The chief organelle that is responsible for the regulation of cholesterol synthesis is the endoplasmic reticulum. Its careful measurements show that the proteins responsible for sensing sterol respond over a very narrow range of concentrations of cholesterol provide precise control over the synthesis of cholesterol. However, the organ that synthesizes the most significant amount of cholesterol in the liver, and is one of the major centers of endogenous cholesterol synthesis.

Stages of cholesterol synthesis 

There are three stages of cholesterol synthesis: oxidation, cyclization, and the loss of three methyl groups resulting in the conversion of squalene to cholesterol. The isoprene units or the isoprenoids are typically a class of large hydrophobic or nonpolar compounds related to this process and are constructed biosynthetically from the five-carbon units.

Steps of cholesterol synthesis 

  • The first step is the synthesis of isopentenyl pyrophosphate and activated isoprene unit, and it acts as the chief building block of cholesterol. 
  • The second step is the condensation of the six molecules of isopentenyl pyrophosphate for the formation of squalene. 
  • The third step is where the squalene cyclizes in a significant reaction with a tetracyclic product that converts into cholesterol. 

Causes of increase in cholesterol synthesis 

Statins are an essential link between cholesterol production and dietary cholesterol absorption. When the cholesterol synthesis process is inhibited with statins, it increases the absorption of cholesterol. However, the decrease in the absorption of cholesterol increases cholesterol synthesis. 

Inhibition of Cholesterol synthesis

Acetate (SKF525) and its methyl analog (SKF3301) turn limit having hypercholesterolemic properties inhibit cholesterol synthesis. Also, isopentenyl and farnesyl pyrophosphate the parent sites for the inhibition of the synthesis of cholesterol. 

There is one more compound by the name of Pravastatin that inhibits the cholesterol synthesis in the human hepatoma cell line Hep G2. It inhibits cholesterol synthesis lesser than lovastatin and simvastatin. This inhibition is reflected in the upregulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase and squalene synthase.

Hormone regulation of cholesterol synthesis 

Cholesterol is the chief source of the biogenesis of steroid hormones. As a result, several hormones exert acute effects on cholesterol synthesis or metabolism. When this occurs through the direct impact of the hormones upon regulating the expression or activity of HMG-CoA reductase SREBP-1c or LDLr, it is known as the hormone regulation of cholesterol synthesis.