Cholesterol

Description

Cholesterol is a waxy, fat-like substance, which is found in all cells of the body. It is produced in the liver, but can also be found in some foods. Cholesterol is needed for the body to work properly as it is useful in the production of hormones, vitamin D, and bile acids. Cholesterol is carried in the blood by proteins, by which proteins and cholesterol are combined and called lipoproteins. Two much cholesterol causes gradually buildup of fatty deposits in the blood vessels, leading to problems for blood flow, which could result in heart attack or stroke. There are two types of lipoproteins. Low density lipoprotein is so called bad cholesterol as it delivers cholesterol to the body. High density lipoprotein is good cholesterol as it removes cholesterol from the bloodstream.

Outline

Cholesterol is a kind of derivatives of cyclopentane multiple hydrogen phenanthrenes and is an important component of various parts of membrane phase structure and myelin cells of human being. For the normal person with weight of 70 kg, the body contains about 140 grams of cholesterol. Since the early 18th century, people had already discovered cholesterol from gallstones. At 1816, Chemist Marshall named this kind of lipid-property substance as cholesterol. Cholesterol is widely found and distributed in animal bodies, and is especially most abundant in the brain and nerve tissue. It also has high content in the kidney, spleen, skin, liver and bile. The solubility of cholesterol is similar to that of the fat which is insoluble in water, but easily soluble in ether, chloroform and some other solvents.
Cholesterol is closely related to the body tissues, bile acids and hormones. It is an indispensable substance of animal tissue cells, which is not only involved in the formation of cell membranes, but also as the precursor for the synthesis of bile acids, steroid hormones and vitamin D3. There are two sources of cholesterol with exogenous sources of cholesterol coming from dietary and endogenous sources coming from the body's own endogenous synthesis. The increased exogenous cholesterol can cause feedback inhibition of endogenous cholesterol synthesis. Fat in your diet can boost the cholesterol absorption. Cholesterol can be metabolized into bile acids or steroids. The absorption of cholesterol also depends on the cholesterol intake with high intake causing reduction of the percentage of absorption. The absorption percentage of cholesterol in people at high levels of intake is less than 10% with the rest part excreted through the feces. Dietary cholesterol is absorbed in the form of chylomicrons into the bloodstream. Because cholesterol can’t be dissolved in water and transported in the form of binding with lipoproteins in the blood.
The main physiological function of cholesterol participating in forming cell membranes, myelin, brain, and can be further converted to bile acids and steroid hormones. There are two major lipoproteins which are involved in cholesterol transport: the low density lipoprotein (LDL) and high density lipoprotein (HDL). The former can transport cholesterol from the liver to the cells of whole body tissues, while the later one transports cholesterol from tissue cells back into the liver. The cholesterol level in the blood can reflect the overall metabolism condition of cholesterol. The total cholesterol content in the blood plasma of normal adult of empty stomach is about 2.83~5.17mmol/L. Abnormal cholesterol metabolism could easily lead to deposition of cholesterol in the blood vessel wall, forming atherosclerosis, causing coronary heart disease and stroke.

Cholesterol content of human tissue

Normal person of 70 kg weigh contains about 140 grams of cholesterol in the body; and its rough distribution is listed in the following table. The cholesterol content of various tissues is relatively stable. Moreover, the plasma concentration of cholesterol also keeps stable instead of being like fats and fatty acids which are prone to change.

Table 1. The cholesterol content of various human tissues

Classification

Cholesterol in the body can be classified into free from and bound lipids form (cholesterol ester).

Effect

(1) It is involved in the formation of cell membranes.
(2) It is the raw material for synthesis of bile acids, vitamin D and steroid hormones.
(3) The total amount of serum cholesterol in China normal person serum is approximately 182.5 ± 4.3 mg%. Extra high blood cholesterol level indicates that cholesterol metabolism dysfunction may occur. Serum cholesterol level in patients with coronary atherosclerosis is often high. So the clinically determination of the serum cholesterol levels will help to diagnose certain diseases.

Sources and absorption

Source: (1) exogenous cholesterol coming from dietary. (2)From the body's own endogenous synthesis.
Absorption: cholesterol is absorbed in the intestines and mainly synthesized in the liver, skin and the small intestine mucosa. Dietary cholesterol is mainly absorbed in the form of chylomicrons into the bloodstream. Cholesterol absorption also depends on the amount; the percentage of absorption is reduced upon a high intake of cholesterol. The absorption percentage is lower than 10% upon high intake amount. After free cholesterol is absorbed, 2/3 of them quickly binds to fatty acid and esterified to form cholesterol esters, making the ability of lipoproteins on carrying cholesterol be enhanced. After cholesterol enters into cells, it will be hydrolyzed and degreased by acidic lipase inside the lysosomes. A fraction of cholesterol in the cells is converted into steroid with excess cholesterol being directly discharged to the gut; another fraction of cholesterol is oxidized in the liver into bile acid and excreted together with the bile.
The above information is edited by the Chemicalbook of Dai Xiongfeng.

Transport

There are two major lipoprotein involved in cholesterol transport: the low density lipoprotein (LDL) and high density lipoprotein (HDL). The former can transport cholesterol from the liver to whole body tissue cells with the later one transporting cholesterol from tissue cells back into the liver.

Determination

Serum cholesterol assays include measurement of total cholesterol (CT), free cholesterol (FC) and cholesterol ester (CE).

Food containing high levels of cholesterol

Animal foods contain high content of cholesterol, such as meat, eggs, milk and so on, but there is no cholesterol in plant foods, such as vegetables, fruits, legumes which almost does not contain any cholesterol, so high cholesterol people should avoid eating animal food with selecting plant food being a better choice.
The cholesterol content of animal organs are particularly high, such as lung, kidney, liver, pig intestines, pig spleen, etc., they are high in cholesterol, so you should eat less.
The cholesterol level in animal brain is also very high, especially in porcine brain, followed by bovine brain, sheep brain, brain duck, and chicken brain, etc. So to prevent high cholesterol, eat less of this kind of food.
Food of low-cholesterol content: lean meat, rabbit meat, yellow croaker, hairtail, skinless chicken, carp, eel, ham square, white fish, jellyfish, milk, and sea cucumber.
Food containing high levels of cholesterol (parentheses lists the number of milligrams of cholesterol per 100 grams of food contains).
Animal brain has the highest cholesterol content: as porcine (3100 mg), bovine brain (2670 mg), sheep brain (2099 mg).
Followed by yellow eggs: duck eggs as yellow (2110 mg), egg yolk (1705 mg), quail’s egg yolk (1674 mg), yellow egg (1132 mg).

Harm of high cholesterol

High cholesterol is clearly related to the occurrence of atherosclerosis. Modern molecular biology has showed that atherosclerotic lesions are initially begun with fatty streaks and atherosclerotic plaque disease, which is formed by macrophages which swallowed cholesterol and smooth muscle cells. On the other hand, high content of cholesterol, high blood pressure can cause harm to the integrity and function of vascular endothelium, resulting in a series of secondary damage. US National Cholesterol Education Program states: normal adult plasma cholesterol levels should be less than 5.2mmol/L; 5.2~6.2mmol/L is the high limit. For guys which exceed the upper limit should change their diet with further examination of high-density lipoprotein and low-density lipoprotein, and select related drugs for treatment. Clinical data have shown 8.5% drop in blood cholesterol and 12.6% decrease in LDL can reduce the mortality of coronary heart disease by 24% as well as reduce the incidence of myocardial infarction by 19%.

Prevention

(1) Low-fat diet.
(2) Exercise. Saturated fatty acids cause the increase of serum cholesterol while unsaturated fatty acids reduce it. Mental workers have higher serum cholesterol levels than manual workers with exercise being able to reduce it.

Uses

1. Used as the raw materials and biochemical research of brain phospholipids cholesterol flocculation test, vitamin D, and hormones.
2. Used for biochemical reagents and emulsifiers.
3. Used for the production of artificial bezoar, preparation of hormone drugs , also can be used as an emulsifier.
4. Used as emulsifiers; as the raw materials of synthesizing artificial bezoar, vitamin D, LCD, and hormone ; used for chemical and biological research.
5. It is an important raw material for manufacturing hormones, and can be used as an emulsifier; also used as reference analysis sample.

Production methods

1. Extracted from pig brain (or spinal cord) or sheep brain.
2. Use the brain tissue of livestock as the raw materials.
Preparation of dry powder: take fresh animal brain and spinal cord (remove the fat and spinal cord membranes), mince, dry at 40-50 °C to obtain the brain dry powder.
Brain (pig, cattle, sheep) [40-50 °C] → brain dry powder
Preparation of crude cholesterol crystals: brain powder is impregnated in 1.2 times the amount of acetone with constant stirring for extraction of 4.5h, and extract for continuously 6 times, filtrate, combine the extract, distill to recycle the acetone and obtain a yellow solid substance. Add 10 times the amount of ethanol, heat and reflux for 1h to obtain the cholesterol ethanol solution, filter and the filtrate is further cooled at 0-5 °C, stand static, separate out the crystals, filter gain to obtain the crude crystals of cholesterol.
Brain dry powder [acetone] → yellow solid [ethanol] → cholesterol ethanol solution [0-5 °C] → crude cholesterol crystals.
Making refined cholesterol: Take the crude cholesterol crystals and add 5 fold the amount of ethanol, add 5%-6% sulfuric acid, heat and reflux for 8h to obtained the hydrolysis liquid, further cool it at 0-5 °C, separate out the crystals, filter to obtain the crystals, add ethanol and wash to being neutral. The crystals washed into neutral were further added into 10 times the amount of 95% ethanol together with 3% activated carbon, heated for reflux and decolorization for 1h, insulate and filter, the filtrate was subject to cooling crystallization at 0-5 °C, repeated three times, filter, collect the crystals, compress for drying, evaporate the ethanol, and vacuum dry at 70-80 °C and obtain the refined cholesterol.
The crude cholesterol crystals [ethanol, H2SO4] → [8h] hydrolysis liquid [0-5 °C] → crystal [ethanol, activated carbon] → [1h] refined cholesterol.
3. Bovine spinal cord is used as raw materials, extract it using petroleum ether and then repeatedly refine to obtain the product.

Precautions

Daily intake of cholesterol for normal adult should be less than 500 mg which is proper with patients suffering coronary heart disease should not exceed 300 mg.

References

1. https://www.nhlbi.nih.gov
2. https://medlineplus.gov/cholesterol.html
3. https://en.wikipedia.org/wiki/Cholesterol
4. https://heartuk.org.uk/health-and-high-cholesterol
5. https://familydoctor.org 

Description

Cholesterol is a soft waxy substance that is a steroidal alcohol or sterol. It is the most abundant steroid in the human body and is a component of every cell. Cholesterol is essential to life and most animals and many plants contain this compound. Cholesterol biosynthesis occurs primarily in the liver, but it may be produced in other organs. A number of other substances are synthesized from cholesterol including vitamin D, steroid hormones (including the sex hormones), and bile salts. Cholesterol resides mainly in cell membranes.
Humans produce about 1 gram of cholesterol daily in the liver. Dietary cholesterol is consumed through food. High cholesterol foods are associated with saturated fats and trans-fatty acids (commonly called trans fats). Dietary cholesterol comes from animal products (plants contain minute amounts of cholesterol) such as meats and dairy products.

Chemical Properties

White to faintly yellow cryst. powder

Chemical Properties

Cholesterol occurs as white or faintly yellow, almost odorless, pearly leaflets, needles, powder, or granules. On prolonged exposure to light and air, cholesterol acquires a yellow to tan color.

History

Cholesterol was discovered in 1769 by Poulletier dela Salle (1719–1787), who isolated the compound from bile and gallstones. It was rediscovered by Michel Eugène Chevreul (1786–1889) in 1815 and named cholesterine. The name comes from the Greek words khole meaning bile and steros meaning solid or stiff . The “ine” ending was later changed to “ol” to designate it as an alcohol.

Uses

Cholesterol be used as pharmaceutical intermediates and be used as synthetic materials of liquid crystal polymers.

Uses

cholesterol is a moisturizer and emollient that acts as a powerful emulsifier in water-in-oil systems. Cholesterol is a fat-like substance found in plant and animal cells. It is also present in the secretion of the sebaceous glands and, therefore, is a component of the fat on the skin’s surface. It is considered a noncomedogenic raw material. It may sometimes be obtained from sheep’s wool wax.

Uses

analeptic, antibacterial

Uses

Cholesterol is commonly associated with cardiovascular disease and its routine measurement is used to measure its potential health risk. High blood serum cholesterol levels are often correlated with excessive plaque deposits in the arteries, a condition known as atherosclerosis or hardening of the arteries. Although high total blood cholesterol levels are associated with heart disease, it is important to distinguish between types of cholesterol when interpreting cholesterol levels. Cholesterol has been labeled as good and bad depending on its physiological role. Forms of cholesterol depend on the lipoproteins that are associated with it. Lowdensity lipoprotein cholesterol (LDL cholesterol) is often referred to as bad cholesterol and high-density lipoprotein (HDL) is identified as good cholesterol. An understanding of the difference between LDL and HDL cholesterol requires an understanding of substances associated with cholesterol in the body. Cholesterol is a lipid so it has very low solubility in water and blood. For the cholesterol synthesized in the liver to be delivered by the bloodstream to the rest of the body, the liver manufactures lipoproteins that can be viewed as carriers for cholesterol (and triglycerides).

Uses

Cholesterol is a major component of all biological membranes; ~25% of total brain lipid is Cholesterol. Cholesterol is the principal sterol of the higher animals. Cholesterol was found in all body tis sues, especial in the brain, spinal cord, and in animal fats or oils. Cholesterol is the main constituent of gallstones.

Definition

ChEBI: A cholestanoid consisting of cholestane having a double bond at the 5,6-position as well as a 3beta-hydroxy group.

Definition

cholesterol: A sterol occurringwidely in animal tissues and also insome higher plants and algae. It canexist as a free sterol or esterified witha long-chain fatty acid. Cholesterol isabsorbed through the intestine ormanufactured in the liver. It servesprincipally as a constituent of bloodplasma lipoproteins and of thelipid–protein complexes that formcell membranes. It is also importantas a precursor of various steroids, especiallythe bile acids, sex hormones,and adrenocorticoid hormones. Thederivative 7-dehydrocholesterol isconverted to vitamin D₃ by the actionof sunlight on skin. Increased levelsof dietary and blood cholesterol havebeen associated with atherosclerosis,a condition in which lipids accumulateon the inner walls of arteries andeventually obstruct blood flow.

Production Methods

The commercial material is normally obtained from the spinal cord of cattle by extraction with petroleum ethers, but it may also be obtained from wool fat. Purification is normally accomplished by repeated bromination. Cholesterol may also be produced by entirely synthetic means.
Cholesterol produced from animal organs will always contain cholestanol and other saturated sterols.

General Description

Cholesterol is a minor sterol present in plants. It is majorly associated with the plant membranes and is a constituent of leaf surface lipids.

Hazard

Questionable carcinogen.

Pharmaceutical Applications

Cholesterol is used in cosmetics and topical pharmaceutical formulations at concentrations of 0.3–5.0% w/w as an emulsifying agent. It imparts water-absorbing power to an ointment and has emollient activity.
Cholesterol also has a physiological role. It is the major sterol of the higher animals, and it is found in all body tissues, especially in the brain and spinal cord. It is also the main constituent of gallstones.

Biochem/physiol Actions

Cholesterol is a lipid that makes up about 20-25% of the structural components of the cell membranes. It determines the fluidity and permeability of the membrane, making it permeable to water but not to ions and protons. Cholesterol also regulates the functions of the transporters and signaling proteins present on the plasma membrane. The major sites of cholesterol synthesis are small intestine and liver.

Safety Profile

Experimental teratogenic and reproductive effects. Questionable carcinogen with experimental carcinogenic and tumorigenic data. Mutation data reported. Used in pharmaceutical and dermal preparations as an emulsifying agent. When heated to decomposition it emits acrid smoke and irritating fumes.

Safety

Cholesterol is generally regarded as an essentially nontoxic and nonirritant material at the levels employed as an excipient. It has, however, exhibited experimental teratogenic and reproductive effects, and mutation data have been reported.
Cholesterol is often derived from animal sources and this must be done in accordance with the regulations for human consumption. The risk of bovine spongiform encephalopathy (BSE) contamination has caused some concern over the use of animalderived cholesterol in pharmaceutical products. However, synthetic methods of cholesterol manufacture have been developed.

target

VEGFR | mTOR

storage

Cholesterol is stable and should be stored in a well-closed container, protected from light.

Purification Methods

Crystallise cholesterol from ethyl acetate, EtOH or isopropyl ether/MeOH. [Hiromitsu & Kevan J Am Chem Soc 109 4501 1987.] For extensive details of purification through the dibromide, see Fieser [J Am Chem Soc 75 5421 1953] and Schwenk and Werthessen [Arch Biochem Biophys 40 334 1952], and by repeated crystallisation from acetic acid; see Fieser [J Am Chem Soc 75 4395 1953]. Like many sterols, cholesterol gives colour reactions with conc H2SO4: When cholesterol is dissolved in a small volume of CHCl3 and mixed with conc H2SO4, the colour of the organic layer becomes crimson, then changes to purple and on further standing in air it turns to blue, then green and finally yellow. The H2SO4 layer develops a green fluorescence. [Beilstein 6 III 2607, 6 IV 4000.]

Incompatibilities

Cholesterol is precipitated by digitonin.

Regulatory Status

Included in the FDA Inactive Ingredients Database (injections; ophthalmic, topical, and vaginal preparations).
Included in nonparenteral medicines licensed in the UK. Included in the Canadian List of Acceptable Non-medicinal Ingredients.