Place of statins among lipid-lowering drugs
In modern pharmacology, drugs affecting lipid metabolism are divided into five main groups depending on their sites of action:
- Statins — cholesterol synthesis (HMG-CoA reductase) inhibitors.
- Cholesterol absorption inhibitors — blockers of intestinal sterol transporters that reduce the incorporation of cholesterol into chylomicrons (e.g., ezetimibe).
- Bile acid sequestrants — drugs that bind bile acids in the gastrointestinal lumen (e.g., cholestyramine).
- Fibrates — fibric acid derivatives that activate lipoprotein lipase (e.g., gemfibrozil).
- Nicotinic acid derivatives — triglyceride lipase inhibitors (e.g., niacin).
Biochemical target and enzymatic block
Under normal conditions, cholesterol biosynthesis in the body proceeds through a series of successive stages: from acetyl-CoA through the formation of mevalonic acid to the end product. The key stage here is the conversion of 3-hydroxy-3-methylglutaryl-coenzyme A to mevalonate.
Statins act as competitive inhibitors of the enzyme HMG-CoA reductase, which is responsible for this regulatory step. By blocking this enzyme, the drugs interrupt the chain of cholesterol synthesis reactions inside liver cells, which sharply reduces the internal lipid stores in hepatocytes.
Compensatory mechanism of LDL receptor activation
The reduction of cholesterol synthesis inside hepatocytes triggers a cascade of cellular defense reactions aimed at replenishing the deficit:
- The concentration of free cholesterol inside the cell drops.
- A special transcription factor SREBP (sterol regulatory element-binding protein) is activated.
- The expression of the gene responsible for the synthesis of low-density lipoprotein receptors is upregulated.
- A greater number of LDL receptors are expressed on the surface of liver cells.
- Uptake and clearance of LDL from the bloodstream increase, leading to a marked decrease in total plasma cholesterol.
Statins block the cholesterol BUILDER (HMG-CoA reductase), causing the liver to starve and actively capture LDL from the blood using new receptors.
Class and exam questions
Which enzyme do statins inhibit?
Statins are competitive inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase), the key enzyme of cholesterol synthesis.
Which agents belong to the statin group?
The main representatives of the group include simvastatin, atorvastatin, rosuvastatin, and lovastatin.
Why does the blood LDL level decrease during statin therapy?
Due to the blockade of cholesterol synthesis inside the hepatocyte, the SREBP factor is activated, the number of LDL receptors on the cell surface increases, and the liver intensively clears LDL from the plasma.
What else to study on this topic
- Structure and role of cholesterol in the body
- Pathways of cholesterol metabolism in various tissues
- Transport forms of lipoproteins and their role in atherogenesis
- Possibility of coenzyme Q synthesis in the body
- Combination therapy of statins with ezetimibe
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