Lipids PDF - Cell Biology

## Lipids Lipids serve two major functions in cells and tissues: energetic and structural. Lipids occur as structural components forming the basic structure of all types of cell membranes representing ~50% of their weight. In addition, lipids may be stored inside cells as a reserve of energy. Moreo...

## Lipids Lipids serve two major functions in cells and tissues: energetic and structural. Lipids occur as structural components forming the basic structure of all types of cell membranes representing ~50% of their weight. In addition, lipids may be stored inside cells as a reserve of energy. Moreover, lipids play a crucial role in terms of communication between different cell types and different organs since many hormones are lipid molecules. Lipids play a crucial function in intracellular signaling. ### Saponifiable Lipids Lipids are either saponifiable (able to make a saponification reaction) or non saponifiable. Lipids having fatty acids among their components are saponifiable while those without fatty acids are not saponifiable. The most common lipids that include fatty acids are neutral fats (triglycerides), phospholipids and glycolipids and cerides. #### Fatty Acids Fatty acids are amphipathic molecules since they consist of long hydrocarbon chains that end by a carboxyl COOH group. Their general formula is $CH_3-(CH_2)_n-COOH$ where *n* is an even number ranging between 2 to 20 for nearly all naturally occurring fatty acids. Fatty acids sparingly occur as free molecules; instead, they are esterified (linked by an ester bond) by other components such as glycerol. The hydrocarbon tail of fatty acids may be saturated or not. It is said to be unsaturated if at least one double bond occurs in the chain, otherwise it is saturated. * **Monounsaturated fatty acids** have one single double bond. * **Polyunsaturated fatty acids** have two or more double bonds. The number of double bonds in the hydrocarbon chain of unsaturated fatty acids may be up to six. Fats rich in saturated fatty acids are solid at room temperature (e.g. animal fats, butter) whereas unsaturated fatty acids are liquid at the same temperature (e.g. oils extracted from plants). Unsaturation degree (number of double bonds) as well as the length of the fatty acid hydrocarbon chain determine the fluidity degree of the lipid and thus the cell membrane which they form. Among the most commonly occurring saturated fatty acids in animal cells there are: * butyric acid (n=2, total of 4 carbons, 4:0) * myristic acid (n = 12, total of 14 carbons, 14:0) * palmitic acid (n = 14, total of 16 carbons, 16:0) * stearic acid (n = 16, total of 18 carbons, 18:0). Three examples of unsaturated fatty acids occur abundantly in olive oil are: * oleic acid [$CH_3-(CH_2)_7-CH=CH-(CH_2)_7-COOH$] * linoleic acid [$CH_3-(CH_2)_4-CH=CH-CH_2-CH=CH-(CH_2)_7-COOH$] * arachidonic acid (total of 20 carbons, 20:4) Although fatty acids differ by their carbon atom number and unsaturation degree, all of them are amphipathic molecules. That is, all fatty acids have a polar (hydrophilic) head which is the COOH group, and a non polar (hydrophobic) tail, which is the remaining part of the molecule. Fatty acids are highly energetic molecules, more energetic than carbohydrates. They are oxidized in mitochondria and peroxisomes and transformed into energy, $H_2O$ and $CO_2$. #### Triglycerides (Neutral fats) Triglycerides or triacylglycerols neutral fats since they lack ionizable or polar (hydrophilic) groups. They result from the esterification of three fatty acid molecules by the three hydroxyl groups of a glycerol molecule. Triglycerides are diverse since different fatty acids may form the ester bonds with the three hydroxyl groups of glycerol. Such neutral fats represent the major stored lipids in certain cell types (adipose tissue in animals, seeds of many plants) as a reserve of energy. * **Monoglycerides** and **diglycerides** contain one and two fatty acids, respectively, in addition to glycerol. Since triglycerides comprise fatty acids, they can form soap molecules (after hydrolysis of the ester bonds) by forming ionic bonds between the $COO^-$ group of the fatty acid molecules and metal ions supplied by the base, usually sodium or potassium. Triglycerides hydrolysis is achieved by lipases as well as by alkaline medium + heating. #### Phospholipids Phospholipids form the basic structure of cell membranes. Unlike triglycerides, phospholipids are amphipathic molecules having a large polar head and long hydrophobic tails. Phospholipids are diverse because of the diversity of their composing fatty acids. They may be divided into two main groups: * **glycerol-derived phospholipids** * **sphingosine-derived phospholipids** **Glycerol-derived phospholipids** (also named glycerophosphatides) are structurally similar to triglycerides except that the third OH of the glycerol molecule is linked to a phosphate group instead of a fatty acid which confers glycerophosphatides their amphipathic property. Importance of the hydrophilic head may be boosted by linking of polar molecules such as choline, serine, ethanolamine and inositol, to the phosphate group. The derivatives of the phosphatidic acid are named according to the name of the added molecule. For instance, phosphatidylcholine, phosphatidylserine, phosphatidyl-ethanolamine and phosphatidylinositol, are phosphatidic acids linked with choline, serine, ethanolamine and inositol, respectively. **Sphingolipids** or **sphingophospholipids** (sphingosine-derived phospholipids) have a global structure (hydrophilic head linked to two hydrophobic tails) that is equivalent to that of glycerophosphatides. Nevertheless, sphingolipids do not contain glycerol. They are derivatives of sphingosine which is an amino-alcohol that has a long unsaturated hydrocarbon chain, one $NH_2$ where the fatty acid is linked and a terminal OH group where phosphate is added. The sphingosine linked to a fatty acid is named ceramide. Therefore, one of the two hydrophobic tails of sphingolipids belongs to the fatty acid and the other to the sphingosine molecule. Phosphate group may be coupled to choline or other polar groups from those previously mentioned. Thus, sphingophospholipids, are amphipathic lipids that contribute to formation of membrane structure. For instance, the myelin sheath surrounding many nerve cells is particularly rich in sphingomyelin where the amino group of the sphingosine skeleton is linked to a fatty acid and the hydroxyl group is esterified by phosphorylcholine. #### Glycolipids The outer surface of the plasma membrane of most cells is coated with short chains of sugars. These are either parts of glycoproteins or they are attached to lipids, thereby forming glycolipids. Glycolipids represent up to 5% of outer lipid layer. In the plasma membrane, glycolipids play crucial roles in immunity, blood group determination, and cell-cell recognition. The main structural difference between phospholipids and glycolipids is the presence of a sugar motif instead of phosphate linked to the the third OH group of glycerol (or the OH of sphingosine). So, similarly to the two previous subtypes of phospholipids, glycolipids are divided into two types: * the glycerol-derived glycolipids * the sphingosine-derived glycolipids **Glycerol-derived glycolipids:** most glycolipids that occur in bacteria and plant cells are composed of glycerol that esterifies two fatty acids (the same manner as in glycerophosphatides) and the third OH group of glycerol serves to link carbohydrate motifs (instead of phosphate). **Sphingosine-derived glycolipids** (glycosphingolipids) are most glycolipids in animal cells. They have the same structure as sphingophospholipids except that there is no phosphate group. In fact, instead of phosphate, at the same position, there are carbohydrate motifs. Carbohydrates bound to lipids may be simple oses (e.g. glucose, galactose) thereby forming the class of **cerebrosides** which are the simplest glycolipids. An example is galactocerebroside that contains galactose and is abundant in the myelin sheath in brain tissue representing about 40% of outer lipid layer weight. Another example is glucocerbroside which contains glucose. Carbohydrates linked to lipids may be also oligosaccharides (branched or unbranched) containing modified oses thereby forming the class of gangliosides. #### Cerides Cerides are esters of fatty acids with fatty alcohol. A fatty alcohol is a long hydrocarbon tail ended by a hydroxyl group OH. It esterifies a fatty acid forming a ceride. The family of cerides is abundant in cork and leaf cuticle as well as in bee wax. An example of cerides is the cetylic alcohol ($CH_3-(CH_2)_{15}-OH$) that makes and ester bond with fatty acids such as palmitic acid ($CH_3-(CH_2)_{14}-COOH$). #### Fatty acids derivatives Certain lipids derive from certain fatty acids. Eicosanoids (such as leukotrienes and prostaglandins) derive from the oxidation and cyclization of certain C20 polyunsaturated fatty acids (e.g. arachidonic acid). They are autocrine and paracrine hormones involved in inflammation, contraction of smooth muscles, the regulation of metabolism, and in platelet aggregation. ### Nonsaponifiable lipids: Steroids and terpenes Nonsaponifiable lipids do not contain fatty acids and are mainly steroids or terpenes which are two distinct classes. They are made of isoprene as a forming unit. #### Terpenes Terpenes are polyprenyl molecules include certain fat-soluble vitamins such as vitamin A, E and K, carotenoids and other pigments such as lycopene, which is abundant in some plant roots, petals, fruits and leaves. * **Tomato red color** is due to lycopene and **carrot root color** is due to carotene. Many terpenes are characterized by a cyclic structure at one pole of the molecule, the cycle results from intramolecular reaction in the propene polymer. At the opposite pole, some terpenes have a hydrophilic group (e.g. OH group) which provides them moderate amphipathic property. #### Steroids Steroids form an important class of lipids composed of complex cyclic molecules on which diverse chemical groups are branched at different carbon atoms. All steroids are derivatives of the perhydrocyclopentano-phenanthrene (= nonlinear arrangement of 3 cyclohexanes and a cyclopentane). Steroids have different physiological properties and roles according to the nature of the chemical groups that are attached to the basic cyclohexanes and cyclopentane. Some steroids are hormones (such as estrogen, progesterone, testosterone and corticosterone and other adrenal hormones) that are involved in communication between cells and organs and in the control of vital physiological processes. Other steroids are vitamins such as vitamin D which is indispensable for normal growth and bone development. Vitamin D is produced in the skin from its precursor (cholesterol) under effect of UV sun rays. In addition to their function as hormones, steroids play a structural role. Cholesterol contributes to cell membranes structure although it is not as amphipathic as phospholipids. The OH group on the first cyclohexane provides a small hydrophilic head responsible for the mild amphipathic character of cholesterol. Cholesterol may represent up to 50% (in molarity) of membrane lipids in certain animal cell types and its presence affects membrane fluidity. Cholesterol acts as a bidirectional regulator of membrane fluidity because at high temperatures, it stabilizes the membrane and raises its melting point, whereas at low temperatures it intercalates between the phospholipids and prevents them from clustering together and hardening. Cholesterol is especially abundant in animal products such as eggs, butter, meat (liver) and cheese. It is true that excess of cholesterol is a major cause of cardiovascular diseases; however, cholesterol is crucial to many vital processes such as production of vitamin D, synthesis of bile salts and sex and adrenal hormones and many other steroides. ### Hydrophobic interactions of lipids in water Cells and their environments are aqueous solutions since water represents up to 90% of a cell weight. Behavior of amphipathic lipids in aqueous solutions made easy the understanding of the structural organization of lipids in cell membranes. Obviously, water cannot dissolve lipids although it is called the "universal solvent". Water can dissolve salts and polar nonionic compounds such as sugar and alcohol and other molecules that contain OH group, aldehyde group and ketone group. Molecules that contain polar and non polar group (such as soaps, fatty acids and glycerophosphatides) do not dissolve in water, but they do form micelles (or micellar arrangement) and/or lipid layers. When amphipathic molecules are vigorously mixed with water, they form a suspension or heterogeneous solution. In such suspension, amphipathic molecules (e.g. glycerophosphatides) form monolayers, bilayers, liposomes and micelles. These structures are adopted by amphipathic molecules so that the hydrophobic tails are close to one another; they are directed away from water avoiding contact with it. The force that keeps the hydrophobic tails together is known as hydrophobic interaction. So, micelles and lipid layers are stabilized by the hydrophobic interactions among the nonpolar hydrocarbon tails. Hydrophobic interactions are actually the most important forces that promote formation and stabilization of all cell membranes. Micelles are microscopic spherical structures (20 to 100 nm) where the polar heads of amphipathic molecules are arranged at the surface of the sphere and interact with the surrounding $H_2O$ molecules through ionic and hydrogen bonds, and the hydrophobic tails are directed inwardly to avoid contact with water. Bilayers are formed within the solution in a way that excludes contact of the hydrophobic tails with water molecules. When a lipid bilayer is large enough, it may fold back and form an artificial spherical vesicle named liposome that encloses a hydrophilic lumen. The central region in a lipid bilayer is totally hydrophobic and forms a barrier against large hydrophilic compounds. This barrier is not completely impermeable since it allows diffusion of small hydrophilic molecules among the lipid molecules.