Cholesterol has a wide range of physiological effects in the body, but when excessive, it can lead to hypercholesterolemia and have adverse effects on the body. Modern research has found that atherosclerosis, venous thrombosis and cholelithiasis are closely related to hypercholesterolemia. If it is simply high cholesterol, dietary regulation is the best method. If it is also accompanied by hypertension, it is best to monitor blood pressure and use antihypertensive drugs as long as it is confirmed by a doctor as hypertension. Hypercholesterolemia is a very important cause of atherosclerosis, so please pay attention.
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Cholesterol in nature is mainly found in animal foods, with a few plants containing cholesterol and most plants containing substances that are structurally similar to cholesterol - plant sterols. Plant sterols have no atherogenic effect. In the intestinal mucosa, plant sterols (especially sitosterol) can competitively inhibit the absorption of cholesterol. The following are common laboratory synthesis methods for reference.
Method 1:
The process of cholesterol synthesis is relatively complex, with nearly 30 steps of reaction, and the entire process can be divided into three stages
Generation of 1.3-light 3-methylglutaraldehyde COA (HMGCOA)
In the cytoplasm, three molecules of ethylene glycol COA are catalyzed by thiolyase and HMGCOA synthase to generate HMGCOA, which is the same mechanism as ketone body formation. However, the intracellular localization is different, and this process occurs in the cytoplasm, while ketone body generation occurs in the mitochondria of liver cells. Therefore, there are two sets of isoenzymes in liver cells that undergo the above reactions respectively.
2. Generation of mevalonic acid (MVA)
Under the catalysis of HMGCOA reductase, HMGCoA consumes two molecules of NADPH+H+to form methyloleic acid (MVA)
This process is irreversible, and HMG CoA reductase is a rate limiting enzyme for cholesterol synthesis.
3. Cholesterol production
MVA undergoes phosphorylation, deproteinization, dealkylation, and condensation to generate squalene containing 30C, which is then catalyzed by endoplasmic reticulum cyclase and oxygenase to produce lanolin sterol. The latter undergoes multiple reactions such as redox and ultimately loses three Cs, resulting in the synthesis of 27C cholesterol.
Method 2:
Using acetyl CoA and palmitic acid as raw materials β- The process of synthesizing cholesterol through the ketoglutarate pathway can be roughly divided into the following steps:
1. Acetyl CoA and palmitic acid are condensed into acetyl CoA under the action of acetyl CoA thiolyase. This reaction is a thiolysis reaction, and the product acetylacetyl CoA is a five membered ring compound. The chemical equation for this step is as follows:
CH3CO-CoA + CH2(COOH)CH2CH2CH2CH3 → CH3CO-CoA + CH3CO-CoA
2. AcetylacetylCoA reacts with triphosphoglycerate under the catalysis of HMG-CoA synthase to generate HMG-CoA. This reaction is a condensation reaction, and the product HMG-CoA is a six membered ring compound. The chemical equation for this step is as follows:
CH3CO-CoA + H2O → HMG-CoA + CH3COOH
3. Under the action of HMG-CoA lyase, HMG-CoA is cleaved into mevalonate. This reaction is a cracking reaction, and the product mevalonate is a five membered cyclic compound. The chemical equation for this step is as follows:
HMG-CoA → CH2=CH (CH2) 3CHO + CO2
4. Under the action of mevalonate kinase, mevalonate reacts with ATP to produce mevalonate pyrophosphate. This reaction is a phosphorylation reaction, and the product mevalonate pyrophosphate is a high-energy compound. The chemical equation for this step is as follows:
CH2=CH(CH2)3CHO + C3H7ClN2O2S → CH2=CH (CH2) 3OPP + C10H15N5O10P2
5. Under the action of squalene cyclase, methylhydroxyvalerate pyrophosphate undergoes cyclization to form squalene. This reaction is a cyclization reaction, and the product squalene is a seven membered cyclic compound. The chemical equation for this step is as follows:
CH2=CH (CH2)3OPP → (CH2)5C=O
6. Under the action of squalene reductase, squalene reacts with NADPH+H+to generate cholesterol. This reaction is a reduction reaction, and the product cholesterol is a six membered ring compound. The chemical equation for this step is as follows:
(CH2)5C=O+NADPH + H+→ CH2OH-(CHOH)4-COOH
Method 3:
The process of synthesizing cholesterol from isopentene pyrophosphate through squalene ring can be roughly divided into the following steps:
1. Isopentene pyrophosphate reacts with ATP under the catalysis of squalene synthase to produce squalene pyrophosphate. This reaction is a phosphorylation reaction, and the product squalene pyrophosphate is a high-energy compound. The chemical equation for this step is as follows:
C5H8O4P + C3H7ClN2O2S → C5H8O4P + C10H15N5O10P2 + C3H7N
2. Squalene pyrophosphate reacts with NADPH+H+under the action of squalene pyrophosphate reductase to generate squalene. This reaction is a reduction reaction, and the product squalene is a seven membered cyclic compound. The chemical equation for this step is as follows:
C5H8O4P-C10H15N5O10P2+ NADPH + H+→ C5H8O + NADP+ + C3H7N
3. Under the action of squalene cyclase, squalene undergoes cyclization to produce cholesterol. This reaction is a cyclization reaction, and the product cholesterol is a six membered cyclic compound. The chemical equation for this step is as follows:
C5H8O + NADP+→ CH2OH-(CHOH)4-COOH + NADPH + H+ + C3H7N
The structure of cholesterol was determined as early as 1930. In 1941, David Rittenberg and KonradBloch discovered that acetic acid labeled with heavy hydrogen was a precursor of cholesterol in rats and mice. Later, it was discovered that the carbon skeleton of the sterol ergosterol in Neurosporarassa was derived entirely from acetic acid. In 1949, J. Bonner and B. Arreguin confirmed that three acetic acid molecules could combine to form a simple five carbon unit, known as isoprene. Their discovery is in line with earlier predictions by Robert Robinson, who believed that cholesterol is a cyclization product of squalene, which can be formed by the polymerization of isoprene. In 1952, Bloch and RLangdon confirmed that squalene can indeed be converted into cholesterol, and they proposed and confirmed a pathway for cholesterol biosynthesis. In 1953, Bloch and R.B. Woodward proposed the idea of cyclization, which was later modified. It was not until 1956 that the unknown isoprene like intermediate was confirmed to be mevalonic acid. The discovery of mevalproic acid has identified an unresolved intermediate link in cholesterol biosynthesis. Since then, the pathways and stereochemistry of cholesterol biosynthesis have been elucidated in detail