Lipids: structure, classification, and functions

Lipids, together with carbohydrates, proteins and nucleic acids, are one of the four main classes of organic molecules found in living organisms.

They are a broad class that includes molecules with different structures in terms of the atoms that constitute them, the types of covalent bonds and the presence or absence of cyclic structures. Example are fatty acids, triglycerides, phospholipids, glycolipids, sterols such as cholesterol and steroid hormones, terpenes such as carotenoids, and vitamins A, D, E and K, called fat-soluble vitamins.
The different lipids have different properties; for example some are soluble in non-polar solvents, others in polar solvents.

Along with carbohydrates and proteins, they are one of the three macronutrients and perform different functions in the body, such as energy stores, electrical and thermal insulators, structural components of membranes, and are involved in the regulation of many cell functions acting as second messengers, hormones and membrane receptors. Moreover, they facilitate digestive process.

Lipid digestion is complicated by the insolubility of many of them in the aqueous environment of the intestine, and requires the intervention, in addition to enzymes, of bile salts, which are cholesterol derivatives. Lipid absorption, too, or more correctly the absorption of products of their digestion, is influenced by the solubility of the released molecules, as is their subsequent transport, storage and use.

Contents

• Structure
• Molecular weight
• Solubility
• Classification
  • Simple lipids
  • Complex lipids
  • Derived lipids
• Functions
• Digestion
• Intestinal absorption
• References

Structure

The simplest lipids are fatty acids, which are carboxylic acids with a hydrocarbon chain of variable length. In most cases the hydrocarbon chain is straight. If there are no double/triple bonds in the chain, fatty acids are called saturated fatty acids, whereas if there are one or more double/triple, they are called unsaturated fatty acids. If the hydrocarbon chain contains two or more double bounds, fatty acids are called polyunsaturated.
Examples of more complex lipids are triglycerides, phospholipids and sterols. Triglycerides consist of three fatty acids attached to a backbone of glycerol. Phospholipids consist of two fatty acids and a phosphate group attached to a backbone of glycerol. In turn, phosphate group can be esterified to an organic molecule such as serine, inositol, choline, or ethanolamine. Sterols differ from other lipids in that they consist of interconnecting rings of carbon atoms, with side chains of oxygen, carbon and hydrogen.

Molecular weight

Unlike many polysaccharides, proteins, and nucleic acids, lipids are not polymers but small molecules, with a molecular weight that vary greatly and range between 100 and 5000 Dalton (Da). For example, acetic acid, the smallest of the fatty acids, has a molecular weight of 60.05 Da, lignoceric acid, one of the very long chain fatty acids, has a molecular weight of 368.37 Da, whereas molecular weight of proteins vary from 5,000-10,000 Da for the smallest, up to a several million for the largest.

Solubility

Lipids are generally considered to be molecules insoluble in polar solvent and soluble in non-polar solvent, and it is true for many of them. However, the presence of atoms such as oxygen, and especially phosphorus, increase the solubility of the molecules, or at least part of them, in polar solvents. For example, the solubility in polar solvents of straight-chain saturated fatty acids is a function of the length of the hydrocarbon chain, which is non-polar, unlike the carboxyl group which is polar. Therefore, while butyric acid, one of the short-chain fatty acids, is soluble in polar solvents, the solubility of caproic acid, caprylic acid, capric acid, and lauric acid, whose hydrocarbon chains are composed from 6, 8, 10, and 12 atoms respectively, gradually decreases.

Saturated fatty acids with chain length greater than 16-18 carbon atoms, namely, from  palmitic acid and stearic acid forward, and therefore also arachidic acid, behenic acid, and lignoceric acids, are insoluble in polar solvents. Other examples of hydrophobic lipids are triglycerides containing long and very long chain fatty acids, and cholesterol esters.
Finally, it should be emphasized that many lipids are amphipathic molecules, namely, molecules that contain both polar and non-polar regions. Examples are fatty acids, phospholipids, glycolipids and cholesterol.

Classification

As with carbohydrate and protein classification, there are several ways to classify lipids. They can be classified based on their physical properties at room temperature, therefore as solids or fats and  liquids or oils, or on the basis of polarity. However, the preferable classification is based on their structure, according to they can be classified in three groups: simple lipids, complex lipids and derived lipids.

Simple lipids

They consist of two types of structural moieties, and include:

• esters of glycerol and fatty acids, such as triglyceride, mono- and diglycerides;
• esters of cholesterol and fatty acids;
• waxes, which are esters of long-chain alcohols and fatty acids, so including esters of vitamins A and D;
• ceramides, that is, amides of fatty acids with long-chain di- or trihydroxy bases containing 12–22 carbon atoms in the carbon chain; an example is sphingosine.

Complex lipids

Unlike simple lipids, complex lipids consist of more than two types of structural moieties, and include, among others:

• phospholipids, that is, glycerol esters of fatty acids, phosphoric acid, and other groups containing nitrogen;
• phosphatidic acid, that is, diacylglycerol esterified to phosphoric acid;
• phosphatidylcholine, also called lecithin, phosphatidylethanolamine, phosphatidylserine, and posphatidylinositol, that is, phosphatidic acid linked to choline, ethanolamine, serine, and inositol, respectively;
• sphingolipids, which are derivatives of ceramides;
• sphingomyelin, that is, ceramide phosphorylcholine;
• cerebrosides, which are ceramide monohexosides, that is, ceramide linked to a single carbohydrate moiety at the terminal hydroxyl group of the base;
• ceramide di- and polyhexoside, that is, linked respectively to a disaccharide or a tri- or oligosaccharide;
• cerebroside sulfate, that is, ceramide monohexoside esterified to a sulfate group.

Derived lipids

They the building blocks for simple and complex lipids, and can occur as such or to be released from the other two major groups.
They include fatty acids and alcohols, vitamins A, D, E and K, hydrocarbons, and sterols.

Functions

Lipids carry out many functions in biological systems. Below is a brief review.

• Fatty acids, stored in cells as triglycerides, are one of the major energy source. They are also the best energy source for humans as they provide, on average, 9 kcal/g whereas carbohydrates and proteins, on average, 4 kcal/g.
• Some lipids are essential nutrients. Examples are vitamin A, essential for healthy vision, vitamin D, essential for calcium metabolism, vitamin E, which prevents the autoxidation of unsaturated lipids, vitamin K, essential for normal clotting of blood, and the essential fatty acids, namely, linoleic acid and alpha-linolenic acid, founders of the family of omega-6 polyunsaturated fatty acids and omega-3 polyunsaturated fatty acids, respectively.
• Phospholipids, cholesterol and glycolipids, together with proteins, are the building blocks for the construction of biological membranes.
• They can act as receptors, antigens and membrane anchors for proteins on plasma membrane, and can modify its structure, and therefore the functionality, of membrane enzymes.
• Many lipids, like diacylglycerol, ceramides, sphingosine and platelet-activating factor act as regulators of intracellular processes.
• Many hormones are lipids.
  Steroid hormones, like estrogens, androgens and cortisol, are synthesized from cholesterol, while prostaglandins, prostacyclins, leukotrienes, thromboxanes, and other compounds, all eicosanoids, arise from omega-3 and omega-6 polyunsaturated fatty acids, such as arachidonic acid and docosahexaenoic acid.
• There are fat deposits not accessed during a fast, classified as structural fat, the function of which is to hold organs and nerves in the right position also protecting them against traumatic injuries and shock. Another example is fat pads on the palms of the feet and hands which protect the bones from mechanical pressure.
• A subcutaneous layer of fat is present in humans. It insulates the body reducing the loss of body heat and contributing to maintain body temperature.
• In epidermis, they are involved in maintaining water barrier.
• They are electrical insulator of axons, which are covered over and over again by plasmatic membranes of Swann cells, in peripheral nervous system, and of oligodendrocytes in central nervous system. This coating is called myelin sheath.
• In digestive tract, they facilitate the digestive process reducing gastric secretion, slowing gastric emptying, and stimulating biliary and pancreatic flow.
• Bile salts are natural detergents synthesized in the liver and secreted into bile. They solubilize phospholipids and cholesterol in the bile, and allow the secretion of cholesterol into the intestine. In fact, the excretion of both cholesterol and bile salts is the major way by which cholesterol is removed from the body.
  Bile salts also aid in lipid digestion, lipid absorption, and the absorption of soluble-fat vitamins in gut.
• In many animals, some lipids are secreted into external environment and act as pheromones that attract or repel other organisms.
• They affect the texture and flavor of food and so its palatability.

Digestion

Unlike carbohydrate digestion and the absorption of monosaccharides, as well as protein digestion and the absorption of amino acids, the digestion of lipids and the absorption of the digestion products must take into account the poorly soluble or completely insoluble nature of many of the molecules involved in the aqueous environment of the intestine .

Digestion starts in the mouth, continues in the stomach and ends in the duodenum, which is the tract of the intestine where the products of digestion are absorbed.
Once reached the stomach, nonpolar lipids aggregate into droplets whose formation is favored by the stirring and mixing actions within the organ and by amphipathic molecules released by the action of lingual and gastric lipases, namely, short-chain fatty acids, medium-chain fatty acids and diacylglycerols. These molecules, by exposing their hydrophilic groups to the aqueous environment and their hydrophobic groups to the hydrophobic interior, which is made up of nonpolar lipids, act as emulsifiers, creating a hydrophilic surface able to interact stably with the surrounding aqueous environment.

In the duodenum, lipid droplets are further emulsified by bile salts and phospholipids present in the bile, which is secreted by the gallbladder. This allows the formation of smaller and smaller droplets, thus increasing the surface available for the action of pancreatic enzymes responsible for digestion of lipids.

Intestinal absorption

With the exception of short- and medium-chain fatty acids, the absorption of lipid digestion products requires the formation of structures that transport nonpolar molecules to the luminal surface of enterocytes. Such structures are called mixed micelles, smaller than lipid droplets and formed by bile salts and lipid digestion products. Their structure resembles a membrane bilayer discs cut out from a biological membrane, where bile salts are arranged on the cutting edges with the hydrophilic region facing the external aqueous environment and the hydrophobic region oriented towards the centre of disk.

Mixed micelles allow lipid concentration to increase up to 1000 times close to the luminal surface of enterocytes, which facilitates lipid absorption. The concentration gradient between the outside and the inside of the enterocyte is also maintained by the rapid intracellular reesterification to cholesterol esters, triglycerides and phospholipids of the absorbed lipids.

The absorption of lipid digestion products occurs through passive diffusion and facilitated transport by specific protein carriers.

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