Table of Contents
- What is Cholesterol?
- Synthesis of Cholesterol
- Regulation of Cholesterol Synthesis
- Frequently Asked Questions
What is Cholesterol?
Cholesterol is an important sterol (a type of lipid) that is biosynthesised in all animal cells. It also forms an essential component of the animal cell membrane. It acts as a precursor for the synthesis of bile acid, steroid hormones and vitamin D. Cholesterol is synthesised in hepatic cells of the liver in large amounts. The synthesis takes place in the cytosol and endoplasmic reticulum of the hepatocytes. Cholesterol is totally absent in prokaryotes, one exception being Mycoplasma which requires cholesterol to grow.
Synthesis of Cholesterol
Cholesterol can be found in our body from two different sources: it is either synthesised de novo in our cells or is taken in the form of dietary cholesterol from different food sources. The de novo synthesis of cholesterol in our cells is enough for our bodily requirements, and there is no need to take cholesterol in dietary supplements.
About 80% of the total cholesterol synthesis takes place in the liver and intestines; the rest being taken place in the brain, reproductive organs and adrenal glands.
Steps of Cholesterol Synthesis
- The synthesis of cholesterol in our body takes place by the mevalonate pathway. It is an important metabolic pathway that produces intermediates necessary for the production of vitamin K, coenzyme Q10, cholesterol and steroid hormones.
- The first step begins with the condensation of two acetyl CoA molecules to form acetoacetyl CoA in the presence of thiolase.
- Next, another molecule of acetyl CoA binds with acetoacetyl CoA to form 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) in the presence of HMG-CoA synthase.
- In the next step, HMG-CoA is reduced to mevalonate in the presence of the enzyme HMG-CoA reductase. This is a rate-limiting step of the cholesterol synthesis pathway.
- Mevalonate is then converted into two active isoprenes, namely isopentenyl-5-pyrophosphate (IPP) and dimethylallyl pyrophosphate (DPP). This step is achieved by two phosphorylation and one decarboxylation reactions. ATP is also used in this step. IPP and DPP are isomers of each other.
- Three molecules of IPP undergo condensation to form farnesyl pyrophosphate in the presence of geranyl transferase.
- Two molecules of farnesyl pyrophosphate then condense to form squalene by the action of the enzyme squalene synthase in the endoplasmic reticulum. Squalene is a 30-carbon compound that serves as a precursor for the synthesis of steroid hormones.
- Next, squalene is cyclised to form lanosterol in the presence of oxidosqualene cyclase.
- Lanosterol, a four-ring compound, then undergoes a series of reactions to form cholesterol. Lanosterol takes the Bloch or Kandutsch-Russell pathway to form cholesterol.
Regulation of Cholesterol Synthesis
De novo synthesis or biosynthesis of cholesterol is dependent on the levels of cholesterol present in our body. When there is a high intake of cholesterol from dietary sources, the endogenous synthesis of the sterol is low, whereas if there is a low intake of cholesterol from dietary sources, the endogenous synthesis rate is high.
HMG-CoA reductase is an important enzyme that can regulate the synthesis of cholesterol in cells. The enzyme has a cytosolic as well as a membrane domain. When the level of cholesterol is high in our body, the membrane domain of HMG-CoA reductase senses the signal for its own degradation and blocks the pathway of cholesterol synthesis.
The membrane domain undergoes changes in its oligomerisation state and becomes a target for destruction by proteasomes.
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Also Read:
- Interesting Facts and Information about Cholesterol
- Difference between Fat and Cholesterol
- Low-Density Lipoprotein Cholesterol – An Overview
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