2. Simple lipids: Triacylglycerols and waxes are classified as simple lipids. The characteristics of each are described in the sections below.

Transcription

1 Paper 4: Biomolecules and their interactions Module 21: Classification of Lipids: simple and compound lipids, phospholipids, Cholesterol OBJECTIVE The main aim of this module is to introduce the students to various subtypes of lipids like simple lipids, compound lipids and derived lipids AND To understand as to how these various lipids help in providing structural integrity to cell membrane and function as storage and signaling molecules in the cell 1. INTRODUCTION Lipids can be divided into three classes: a. Simple lipids b. Compound lipids c. Derived lipids Figure 1 2. Simple lipids: Triacylglycerols and waxes are classified as simple lipids. The characteristics of each are described in the sections below. 1

2 2.1 Triacylglycerols (TAGs)/triglyderides/fats/neutral fats TAGs are constructed from fatty acids and are classified as simple lipids. They consist of 3 fatty acids in ester linkage with a single glycerol molecule that serves as the backbone, as illustrated in Fig. 2. Figure Characteristics of TAGs These are non-polar molecules because of the absence of any available free polar group. The carboxylate groups of the fatty acids are in ester linkage with the hydroxyl groups of the glycerol molecule. TAGs appear as oily droplets in aqueous cytosol, when observed under a microscope. The storage and synthesis of TAGs takes place in adipocytes and in the seeds of plants, which are enriched in the oil droplets as opposed to a normal cell. TAGs are mobilized from their storage sites by lipases that catalyze their breakdown, to provide energy TAGs as energy depots There are two advantages of choosing TAGs as the stored source of energy as opposed to carbohydrates: a. The carbon atoms of the fatty acids are more reduced, compared to those in sugars, which in turn leads to generation of twice as much energy upon their oxidation versus oxidation of sugars. b. TAGs are hydrophobic and hence unhydrated, due to which they do not have to bear with the weight of water of hydration, unlike glycogen (storage form of carbohydrates) molecule that would carry about 2g of water for every gram of stored glycogen. TAGs also serve as insulators in animals such as seals, penguins, polar bears etc. Additionally, TAGs also provide insulation and energy in hibernating animals. 2

3 The low density of TAGs is advantageous in sperm whales, where these lipids are stored in the spermaceti organ located in their large heads. Spermaceti organ contains upto 3600 kg of spermaceti oil, which is a mixture of TAGs and waxes with a large number of unsaturated fatty acids. At normal body temperature of the whales, this mixture is a liquid, while it crystallizes to turn into a solid mass when the temperature drops. The sperm whales usually encounter a temperature drop, when they deep dive into ocean for feeding on squids, their primary food source. For sperm whales to remain still at such depths without much of swimming, they need to match their buoyancy with that of the surrounding water, which is cold and dense at these depths. The crystallization of the spermaceti oil at this low temperature enables these whales to keep afloat during their deep dives. The spermaceti oils turns into a liquid when the whale resurfaces at the surface of the ocean. Sperm whales therefore are a very good example of biochemical and anatomical adaptation. The TAGs and waxes in the spermaceti oil have the right degree of unsaturation and chain length in their fatty acids Waxes Waxes are considered as simplest fatty acid esters in nature. Structurally, they are considered as esters of long-chain (C 14 -C 36 ) saturated and unsaturated fatty acids with long-chain (C 16 -C 30 ) alcohols (Fig. 3). Figure 3 They are the main source of energy in planktons. The melting point of waxes is higher than that of TAGs. Waxes are considered water-repellant due to which certain skin glands secrete them to protect hair and skin by keeping them lubricated. The leaves of plants like rhododendrons, poison ivy and several tropical plants are shiny in appearance due to wax coating on them. This prevents excess evaporation of water and provides protection from the parasites. 3. Compound lipids/conjugated lipids: Defined as esters that contain chemical groups in addition to fatty acids and alcohols. Depending on their chemical groups they are further subdivided into: a. Glycerophospholipids b. Sphingolipids (phosphor- or glycol-) c. Glycolipids (cerebrosides and gangliosides) d. Sulfolipids e. Lipoproteins 3

4 3.1. Glycerophospholipids/Phospholipids are the major structural component of all biological membranes structurally they consist of a glycerol backbone with fatty acids at the C1 and C2 positions, while the C3 position is occupied by a phosphate group attached to a polar moiety termed x as depicted in Fig. 4. Figure 4 these are amphiphilic molecules because they have the hydrophobic fatty acids as well as the polar head groups. If x is an H, the phospholipid is referred to as phosphatidic acid, the simplest form of phospholipid. As shown in Fig. 4 the x can also be a choline moiety, in which case it is referred to as phosphatidylcholine. x can be a serine, ethanolamine also, generating phosphotidylserine and phosphotidylethanolamine, respectively. The C1 position is occupied by a saturated fatty acid of length ranging between C 16 - C 18. The C2 position is occupied by unsaturated C 16 -C 20 fatty acid. The phosphate group imparts a negative charge to the phospholipid molecule, while the charge on the polar head group can vary. Thus, Phosphatidyl 4,5 bisphosphate is a negatively charged phospholipid Phosphotidylserine is neutral and Phosphotidylcholine and ethanolamine have a positive charge Glycerophospholipids with Ether-linked fatty acids In these phospholipids, one of the two fatty acid chain is in a ether linkage with the glycerol backbone. In alkyl ether lipids, the fatty acyl chain may be saturated or may be unsaturated in the case of plasmalogens. The human heart and the membranes of certain halophilic bacteria are enriched in ether lipids. These lipids are resistant to the action by phospholipases, which may be the reason why they are predominant in our heart tissue. The platelet-activating factor, released from the basophils, serves as a signaling molecule to spur the clumping of platelets. A vasoconstrictor, serotonin is thus released from platelets. 4

5 It also serves a role in inflammatory reactions and allergic responses Phospholipases hydrolyze phospholipids Hydrolysis of phospholipids by phospholipases generates specific end products. The chemical structure of a phospholipid can be predicted based on the type of end product generated as depicted in Fig. 5. Figure 5 As an example lysophosphatidic acid is the end product generated after the action of phospholipase A 2 (PLaseA 2 ). The ability of lysophosphatidic acid to act as a detergent is lethal for cell membranes. Bee and snake venoms are enriched in PLaseA 2. The end products most often are not subjected to further degradation in vivo. In such situations, they function as intra- or extracellular signaling molecules. Lysophosphatidic acid in vivo is generated by the hydrolysis of phospholipids within the membrane of the platelets and damaged cells but since it has a very small head group, its production does not lyse the cells. It instead activates cell growth, which is necessary for the repair process of the damaged cells. 1, 2 diacylglycerol (DAG), another molecule which is derived from the phospholipids by the action of PLaseC, serves as an intracellular messenger that activates the protein kinase C cascade. PLaseA 2 or any other phospholipase should be able to gain access into the hydrophobic environment of the plasma membrane, to act on phospholipids. Therefore, solving the X-ray structures of these enzymes has been a fascinating area for biochemists. Amongst the phospholipases, PLaseA 2 is considered the most well characterized lipid-specific enzyme. It is a very small protein of 14 kda (125 amino acid residues). The X-ray structure of PLaseA 2 from cobra venom has been solved and it shows that : a. the active site of the enzyme is occupied by the polar head group, while b. the hydrophobic fatty acid tails, stretch out of the active site to interact with the side chains of many aromatic amino acids Galactolipids and sulfolipids 5

6 Plant membranes are enriched in another class of lipids, namely galactolipids, wherein, The C3 of a 1,2 diacylglycerol molecule is linked to one or two galactose molecules by a glycosidic linkage (Fig. 6). Figure 6 the thylakoid membranes of chloroplasts are enriched in galactolipids. phosphate can be a limiting nutrient for plants, due to which they have galactolipids (phosphate-free) instead of phospholipids. they are also the most abundant lipids in the biosphere additionally, plant membranes also have sulfolipids wherein; a negatively charged sulfonate group replaces the negatively charged phosphate (Fig. 7). Figure Sphingolipids Sphigolipids are also important for the structural integrity of plasma membrane They comprise of a polar head group and two nonpolar tails but no glycerol moiety and are considered as the 4 th largest class of membrane lipids. Sphingolipids contain the following: One molecule of sphingosine/4-sphingenine, which is a long chain amino alcohol or one of its derivatives A polar head group that is linked to the sphingosine molecule by a glycosidic linkage or is in a phosphodiester linkage AND One molecule of a long-chain fatty acid 6

7 The general structure of sphingolipid is shown in Fig. 8, followed by Table 1 showing structures of various sphingolipids. Figure 8. As shown in Table 1, if the X is a H, then the sphingolipid is referred to as ceramide, which is the parent compound for all other sphingolipids. The carbon atoms in sphingosine are numbered starting from the polar head group. These 3 carbons are considered to be analogous to the carbon atoms of glycerol in phospholipids. The fatty acid at C2 position is in an amide linkage with the amino group of sphingosine and can be saturated or unsaturated with a chain length of 16, 18, 22 or 24 carbon atoms. If the X is replaced by a phosphocholine moiety, it is called sphingomyelin. 7

8 Subclasses of sphingolipids Figure 9 The subclasses of sphingolipids differ in their head groups though ceramide remains the backbone for all them. Sphingomyelin (SM) contain phosphocholine or phosphoethanolamine as their head group. As a consequence, they carry the same net charge and have general properties similar to phosphatidylcholine (phospholipid) It comprises of 10-20% of total plasma membrane lipids. SM is abundant in the myelin sheath that surrounds the neurons. Cerebrosides/glycosphingolipids contain one or more sugars as their head group and are abundant in the outer face of the plasma membrane (Fig. 10). Figure 10 The sugar groups are connected to ceramide directly through the OH group at C1 of ceramide. 8

9 Cerebrosides contain a single sugar residue, which can be either galactose or glucose, linked to ceramide (Table 1). Globosides on the other hand contain two or more sugars, which are D-glucose, D-galactose or N-acetyl-D-galactosamine. Both cerebrosides and globosides do not carry any net charge at ph 7, hence are also referred to as neutral glycolipids. Gangliosides contain one or more residues of N-acetylneuraminic acid at their termini (also referred to as sialic acid) and oligosaccharides as the polar head group. The gangliosides carry a negative charge due to the presence of sialic acid. Depending on the number of sialic acid residues the gangliosides are further subdivided into the following categories (Fig. 11): a. GM (M is for mono-) series, that contain one sialic acid at the termini b. GD (D is for di-) series that contain two sialic acid residues c. GT (t for tri-) and so on Figure Derived lipids are defined as lipids obtained after the hydrolysis of simple and compound lipids. Alcohols, fatty acids, aldehydes, ketones, bile acid and sterols are a few examples of derived lipids Sterols Sterols are structural lipids present in the eukaryotic cell membranes. They contain a. a steroid nucleus that has four fused rings AND b. a hydroxyl group that makes sterols amphipathic the fused rings impart rigidity to the sterol molecule as it does not allow free rotation around the C-C bond. 9

10 Cholesterol is the most abundant sterol in the eukaryotic plasma membrane (Fig. 12), while the plant and fungal plasma membranes are enriched in stigmasterol and ergosterol. Figure 12 Bacteria cannot synthesize sterol but have the ability to use exogenous sterols, which they incorporate into their membranes. Five-isoprene subunits are the starting material for the synthesis of sterols. Sterols also serve as precursors of steroid hormones, bile acids etc Cholesterol is the precursor for steroid hormones and vitamin D The classification of steroid hormones is based on the physiological response they are involved in: 1. Glucorticoids have an effect on carbohydrate, protein and lipid metabolism and also influence various other functions such as the inflammatory response. Cortisol is an example of a glucocorticoid. They are synthesized by the cortex of the adrenal gland Impaired functioning of glucocorticoids leads to Addison s disease 2. Mineralocorticoids like aldosterone control the kidney functions 10

11 3. Androgens and estrogens are involved in sexual development. Testosterone, an androgen, is the male sex hormone while estradiol, an estrogen is a female sex hormone. 4. Vitamin D is also a sterol derivative wherein the steroid B ring is disrupted between C9 and C10 (Fig. 13). Figure 13 Vitamin D 2 and D 3 are generally in inactive forms and become active only upon hydroxylation. Vitamin D increases calcium absorption, which in turn increases calcium deposition in the bones and teeth. Deficiency of vitamin D causes rickets in children, while excess of it causes vitamin D intoxication. 5. Summary Lipids are classified as simple, compound and derived which are further divided into various subtypes. Triacylglycerols contain three fatty acids esterified to glycerol and are stored in adipocytes. Glycerophospholipids are amphiphilic molecules with a polar head group and two fatty acyl chains in an ester or ether linkage to glycerol. Sphingolipids, considered as compound lipids are classified into sphingomyelin, gangliosides and cerebrosides. Glycerophospholipids and sphingolipids provide structural integrity to the biological menbranes. Cholesterol is a derived lipid and has a fused four ring structure. Steroid hormones and vitamin D are all based on the four ring structure and serve important biological roles. 11