Triglyceride

Example of an unsaturated fatty triglyceride (C₅₅ H₉₈O₆). Left part: glycerol; right side, top down: palmic acid, oleic acid, alpha-linolenic acid.

A triglyceride (TG, tiglyceride, TAG or triacylglyceride) is an ester derivative of glycerol and three fatty acids (from tri- and glyceride). Triglycerides are the major constituents of body fat in humans and other animals, as well as vegetable fat. They are also present in the blood to allow the bi-directional transfer of adipose fat and blood glucose from the liver, and are an important component of human skin oils (sebum).

There are many different types of triglycerides, with the main division being the saturated and unsaturated types. Saturated fats are "saturated" with hydrogen: all available places where hydrogen atoms could attach to carbon atoms are occupied. These have a higher melting point and are more likely to be solid at room temperature. Unsaturated fats have double bonds between some of the carbon atoms, which reduces the number of places where hydrogen atoms can attach to carbon atoms. These have a lower melting point and are more likely to be liquid at room temperature.

Chemical Structure

Triglycerides are chemically tri-esters of fatty acids and glycerol. Triglycerides are formed by combining glycerol with three fatty acid molecules. Alcohols have a hydroxyl group (HO–). Organic acids have a carboxyl group (-COOH). Alcohols and organic acids unite to form esters. The glycerol molecule has three hydroxyl groups (HO–). Each fatty acid has a carboxyl group (–COOH). In triglycerides, the hydroxyl groups of glycerol join the carboxyl groups of fatty acids to form ester bonds:

RCO2CH2CH(O2CR^{'}) CH2CO2 R^{''} + 3H2O}}}" xmlns="http://www.w3.org/1998/Math/MathML">HOCH2CH(OH)CH2OH+RCO2H+R♫CO2H+R♫CO2HΔ Δ RCO2CH2CH(O2CR♫)CH2CO2R♫+3H2O{displaystyle {ce {HOCH2CH (OH) CH2OH + RCO2H + R^{'}CO2H + R^{'}CO2H - offset RCO2CH2CH(O2CR^{'}) CH2CO2 R^{'} + 3H2O}}}} RCO2CH2CH(O2CR^{'}) CH2CO2 R^{''} + 3H2O}}}" aria-hidden="true" class="mwe-math-fallback-image-inline" src="https://wikimedia.org/api/rest_v1/media/math/render/svg/6abe32f4097ff4ed394bf47810209f9e6295362c" style="vertical-align: -1.005ex; width:108.735ex; height:3.676ex;"/>

The three fatty acids (RCO2H{displaystyle {ce {RCO2H}}}, R♫CO2H{displaystyle {ce {R^{}CO2H}}}}, R♫CO2H{displaystyle {ce {R^{}CO2H}}}}) are generally different, but many types of triglycerides are known. The chain lengths of fatty acids in natural triglycerides vary, but most contain 16, 18 or 20 carbon atoms. Natural fatty acids found in plants and animals are typically composed of only a couple of carbon atoms, which reflects the pathway for their biosynthesis from the CoA acetyl of two-carbon construction blocks. The bacteria, however, possess the ability to synthesize fatty acids from unstoppable and branched chains. As a result, ruminant animal fat contains fatty acids of odd numbers, like 15, due to the action of bacteria in the rumen. Many fatty acids are unsaturated, some are polyunsaturated (e.g., derivatives of linoleic acid).

Most natural fats contain a complex mixture of individual triglycerides. Because of this, they melt over a wide range of temperatures. Cocoa butter is unusual in that it is composed of only a few triglycerides, derived from palmitic, oleic, and stearic acids at the 1-, 2-, and 3-positions of glycerol, respectively.

Homotriglycerides

The simplest triglycerides are those in which all three fatty acids are identical. Their names indicate the fatty acid: stearin derived from stearic acid, palmitin derived from palmitic acid, etc. These compounds can be obtained in three crystalline forms (polymorphs): α, β, and β', the three forms differing in their melting points.

Chirality

If the first and third chains R and R "are different, then the central carbon atom is a chiral center and, as a result, the triglyceride is chiral.

Triaglyceride nomenclature

Condensed structure of a triglyceride.

If the fatty acids are the same, they are named with the prefix tri-, the name of the fatty acid, and the suffix -ine. Example:

• Triolein: sterified glycerol with 3 oleic acid fatty acids.
• Tripalmitin: sterified glycerol with 3 fatty acids of palmite acid.
• Triestearina: sterified glycerol with 3 fatty acids of stearic acid.
• Trimiristin: sterified glycerol with 3 myristic acid fatty acids.
• Trirricinolein: sterified glycerol with 3 fatty acids of ricinoleic acid.

When any of the fatty acids is different, it is a mixed triacylglyceride, they are named the same as monoacylglycerides and diacylglycerides, numbering the fatty acids with the corresponding locant and ending in glycerol. Example: 1-stearoyl-2-oleyl-3-palmitoyl-sn-glycerol (glycerol esterified in position 1 by stearic acid, in position 2 by oleic acid and in position 3 by palmitic acid).

Metabolism

Pancreatic lipase acts on the ester bond, hydrolyzing the bond and "releasing" the fatty acid. In the triglyceride form, lipids cannot be absorbed by the duodenum. Fatty acids, monoglycerides (one glycerol, one fatty acid), and some diglycerides are absorbed by the duodenum, once the triglycerides have been broken down.

In the intestine, after the secretion of lipases and bile, triglycerides are split into monoacylglycerol and free fatty acids in a process called lipolysis. Subsequently, they move to absorptive enterocyte cells lining the intestines. Triglycerides are rebuilt in enterocytes from their fragments and packaged together with cholesterol and protein to form chylomicrons. These are excreted from the cells and collected in the lymphatic system and transported to the great vessels near the heart before mixing with the blood. Various tissues can capture the chylomicrons, freeing the triglycerides to be used as an energy source. Liver cells can synthesize and store triglycerides. When the body needs fatty acids for energy, the hormone glucagon signals the breakdown of triglycerides by lipid hormone-sensitive lipase to release free fatty acids. Since fatty acids cannot be used by the brain for energy (unless converted to a ketone), the glycerol component of triglycerides can be converted to glucose via gluconeogenesis by conversion to dihydroxyacetone phosphate and then into glyceraldehyde 3 phosphate, so that the brain uses it as fuel after its decomposition. Fat cells can also break down for that reason if the brain's needs exceed the body's.

Triglycerides cannot pass through cell membranes freely. Special enzymes in the blood vessel walls called lipoprotein lipases must break down triglycerides into free fatty acids and glycerol. Fatty acids can be absorbed by cells through the fatty acid transporter (FAT).

Triglycerides, as major components of very-low-density lipoproteins (VLDL) and chylomicrons, play an important role in metabolism as sources of energy and transporters of dietary fats. They contain more than twice as much energy (approximately 9 kcal/g or 38 kJ/g) as carbohydrates (approximately 4 kcal/g or 17 kJ/g).

Biosynthesis of triglycerides

The synthesis of triglycerides takes place in the endoplasmic reticulum of almost all the cells of the organism, but it is in the liver, particularly in its parenchymal cells, the hepatocytes, and in the adipose tissue (adipocytes) where this process is most active and of greater metabolic relevance. In the liver, triglyceride synthesis is normally linked to very-low-density lipoprotein (VLDL) secretion and is not considered a physiological storage site for lipids. Therefore, any accumulation of triglycerides in this organ is pathological, and is interchangeably called hepatic steatosis or fatty liver. On the contrary, adipose tissue's main function is the accumulation of energy in the form of triglycerides. However, the pathological accumulation of triglycerides in adipose tissue (obesity) is associated, apparently causally, with a series of endocrine-metabolic abnormalities, the causes of which are currently the subject of intense investigation, given their impact on overall mortality. of the contemporary population. A trace amount of triglycerides is normally stored in cardiac and skeletal muscle, although only for local consumption.

The biosynthesis of triglycerides comprises several reactions:

• Activation of fatty acids. Fatty acids are "activated" (converted into fatty acil-CoA) by conversion into their esters with coenzyme A according to reaction:

• Triglycerides. The synthesis of triglycerides itself, consists of the successive acceleration of the glycerol-3-phosphate skeleton in its three carbon atoms. The first acilation, in carbon 1 (sn1), is catalyzed by the enzyme glycerol-phosphate-acil-transferase (GPAT, for its English acronym) and results in the formation of lisophosphatidic acid. The second acilation (sn2) is catalyzed by the enzyme acil-glycerol-phosphate-acil transferase (AGPAT), generating phosphatidic acid. A stage prior to the formation of diacilglycerol, the direct precursor of triglycerides, is the phosphorylation of phosphatidic acid. This reaction is catalysed by a family of partially characterized enzymes, phosphatase of phosphatedic acid (PPAPs, its English acronym), of which the most studied is the family of lipins. Finally, the sn3 position of the diacilglicerol is catalyzed by the enzyme diacilglicerol-acil-transferase (DGAT). Both phosphatidic acid and diacilglycerol are also precursors of other important glycerols: phosphatdilinositol, phosphatidylglycerol and cardiolipin, in the case of phosphatidic acid; and phosphatidylcholin, phosphatidylserin and phosphatidiletanolamine, in the case of diacilylcerol.

Very relevantly, mutations in the gene encoding the enzyme AGPAT isoform 2 (AGPAT2), the main AGPAT isoform expressed in adipose tissue and liver, cause congenital forms of generalized lipodystrophy (absence of adipose tissue) in human beings. humans. This, plus evidence derived from cell cultures and experimental animals, indicates that there is a close relationship between the biogenesis of adipose tissue and the synthesis of triglycerides. The causal mechanisms of lipodystrophy associated with AGPAT2 mutations are still under investigation.

Role in disease

In the human body, high levels of triglycerides in the bloodstream have been linked to atherosclerosis and, by extension, the risk of heart disease and stroke. However, the relative negative impact of elevated levels of triglycerides compared to that of LDL:HDL ratios is still unknown. The risk can be partly explained by a strong inverse relationship between the triglyceride level and the HDL cholesterol level. But the risk is also due to high triglyceride levels that increase the number of small, dense LDL particles.

Guidelines

Reference ranges for blood tests, which show the usual ranges for triglycerides (which increase with age) in orange to the right.

The National Cholesterol Education Program has established guidelines for triglyceride levels:

These levels are tested after fasting for 8 to 12 hours. Triglyceride levels remain temporarily higher for a period after eating.

The American Heart Association recommends an optimal triglyceride level of 100 mg/dL (1.1 mmol/L) or lower to improve heart health.

Reduce triglyceride levels

Weight loss and dietary modification are effective first-line lifestyle modification treatments for hypertriglyceridemia. For people with mild or moderate triglyceride levels, lifestyle changes are recommended including weight loss, moderate exercise, and diet modification. This may include restricting carbohydrates (specifically fructose) and fat in the diet and consuming omega-3 fatty acids from seaweed, nuts, and seeds. Medications are recommended in those with high triglyceride levels that are not corrected by the above lifestyle modifications, and fibrates are recommended first. Epanova (omega-3-carboxylic acids) is another prescription medication which is used to treat very high levels of triglycerides in the blood.

The decision to treat hypertriglyceridemia with medications depends on the levels and presence of other risk factors for cardiovascular disease. Very high levels that would increase the risk of pancreatitis are treated with a drug from the fibrate class. Niacin and omega-3 fatty acids, as well as drugs of the statin class, can be used together, with statins being the primary drug for moderate hypertriglyceridemia when cardiovascular risk reduction is required.

Industrial uses

Linseed oil and related oils are important components of useful products used in oil paints and related coatings. Flaxseed oil is rich in di- and tri-unsaturated fatty acid components, which tend to harden in the presence of oxygen. This heat-producing hardening process is peculiar to these so-called drying oils. It is caused by a polymerization process that begins with oxygen molecules attacking the carbon skeleton.

Triglycerides are also broken down into their components through transesterification during the manufacture of biodiesel. The resulting fatty acid esters can be used as fuel in diesel engines. Glycerin has many uses, such as in food manufacturing and in the production of pharmaceuticals.

Staining

Staining for fatty acids, triglycerides, lipoproteins, and other lipids is done by using lysochromes (fat-soluble dyes). These dyes can allow the qualification of a certain fat of interest by dyeing the material a specific color. Some examples: Sudan IV, Oil Red O and Sudan Black B.