LIPIDS Lipids ( Greek: lipos, fat) another major group of molecules found in all cells. They are not polymeric and aggregate to form biological membranes (e.g. bilipid layer and proteins that surround the cytoplasm of all cells). They are largely hydrophobic and sparingly soluble in water and do not mix freely in aqueous phase but instead form bilayers. They contain hydrocarbon chains that serve as energy stores. Many intra- and intercellular signaling events involve lipid molecules.

LIPIDS  The term lipids covers a structurally diverse group of compounds.  Lipids are defined as water-insoluble compounds extracted from living organisms by weakly polar or nonpolar solvents.  Biologically, the hydrocarbon content in all lipids is derived from the polymerization of acetate followed by the reduction of the chain so formed.

LIPID CLASSES There is no universally accepted scheme for classifying lipids. However, the polymerization of acetate can give rise to the following: Long, linear hydrocarbon chains – nCH 3 COO -, CH 3 COCH 2 CO…, CH 3 CH 2 CH 2 CH 2 …; These products are fatty acids, CH 3 (CH 2 ) n COOH. Lipids containing fatty acids include: glycerolipids, sphingolipids, and waxes. Branched-chain hydrocarbons – via a 5-carbon intermediate, isopentene (isoprene), 3CH 3 COO - (CH 3 CH=CCH 3 CH 2 -) terpenes. Linear or cyclic structures that are only partially reduced, nCH 3 COO-. These are called acetogenins or polyketides. Many of these are aromatic compounds.

FATTY ACIDS  Fatty acids are carboxylic acids with long-chain hydrocarbon side groups.  In higher plants and animals, the predominant fatty acid residues are those of the C16 and C18 species: palmitic, oleic, linoleic, and stearic acids  Fatty acids with less than 14 or more than 20 carbon atoms are uncommon.

 Most fatty acids are even number of carbon atoms.  Over half of the fatty acid residues of plant and animal lipids are unsaturated (contain double bonds); often polyunsaturated (contain 2 or more double bonds).  The numbering of the carbon atoms starts from the carbon atom in the carboxylic group.

NUMBER NOTATION  A number notation is used widely for indicating structure of fatty acids. Examples:  Saturated fatty acid- that does not contain any double bonds in its hydrocarbon chain. CH 3 (CH 2 ) 14 (COOH)- Palmitic acid, 16:0,(to the left of the colon:) is the no. of C atoms in the acid with ion palmitate CH 3 (CH 2 ) 14 COO -

UNSATURATED FATTY ACID Unsaturated fatty acid- Palmitoleic acid CH 3 (CH 2 ) 5 CH=CH(CH 2 ) 7 (COOH)  The double bond nearly always has the cis conformation (an arrangement of the peptide group in which the successive C α atoms are on the same side of the peptide bond); 16:1 Δ9.  16 represents no. of C atoms in the acid; 1 (right of the colon) represents the no. of bonds; Δ represents the number of carbons between the double bond and the end of the chain, with the carbon of the carboxylic acid group being called C1.

POLYUNSATURATED FATTY ACID  Polyunsaturated fatty acid- the double bonds are rarely conjugated (forming acid [base accepting proton] or base [acid donates a proton]) e.g. Linoleic acid CH 3 (CH 2 ) 4 CH=CHCH 2 CH=CH(CH 2 ) 7 COOH 18:2 Δ9,12  The presence of cis rather than trans (an arrangement of peptide group in which successive C α atoms are on the opposite sides of the peptide bond) double bonds in naturally occurring unsaturated fatty acids ensures that lipids containing fatty acids have a low melting points and are therefore fluid at physiological temperatures.

 Over 100 fatty acids are known to occur naturally. Most consist of linear chains of carbon atoms, but a few are branched.  They occur in very low quantities in the free state and are found mostly in an esterified state as components of other lipids.  The pK a of carboxylic acid group is about 5 under physiological conditions. This group will exit as an ionized state called acylate ion.

GLYCEROLIPIDS – contain glycerol  These lipids contain glycerol in which the hydroxyl groups are substituted and are most abundant in animals.  Triacylglycerols (TAG’s) are neutral glycerolipids also termed as triglycerides.  They are present in the cells of adipose layer to form depot fat (mltg.pt. few degrees below body temperature) and function as a food store.  In the TAG’s, three hydroxyl groups are esterified,usually by different fatty acids.

Glycerolipids contd.  Phosphoglyceralides are polar and are also termed as phospholipids. However, other lipids, not containing glycerol, also contain phosphorus.  Phospholipids are derived from sn-glycerol-3-phosphoric acid (Fig. below, sn- nucleophilic subsstitution reaction following the first order of kinetics) in which the acid moeity is esterified with certain alcohols and the hydroxyl groups on C-1 and C-2 are are esterified with fatty acids. CH 2 OH HOCH O CH 2 O P OH OH

SPHINGOLIPIDS – long-chain bases  Shingolipids are built from long-chain, hydroxylated bases rather than from glycerol. Two such bases found in animals are sphingosine (more common) and sphinganine.  Ceramide is formed when any of these bases is acylated with a fatty acid.  Based on the substitution of the primary hydroxyl group, sphingolipids are divided into 2 classes: i. Phosphosphingolipids – the hydroxyl group is esterified with choline phosphate to another R group and is known as sphingomyelin ii. Glycosphingolipids – the hydroxyl group is substituted with a carbohydrate. 50 types of such lipids are known

TERPENES- branched-chain hydrocarbons  The term terpenes is applied to steam- distilled oils obtained from turpentine.  Most of these compounds are present in the oil having a formula C10H15. Terpenes are multiples of five for oils with more than 10 C atoms e.g. limonene, farnesol, Vitamin A.  Compounds similar to terpenes and that are water-insoluble are distributed widely; large quantities are found in plants, but they also exist in most other living organisms.

STEROIDS- cyclic reduced aromatic hydrocarbons  Steroids are derivatives of reduced aromatic hydrocarbon perhydrocyclopentanophenanthrene e.g. cholesterol (in cell membrane), testosterone (a hormone), cholic acid (a constituent of bile).  These compounds are synthesized in living systems from branched- chain isoprene

CAROTENOIDS- aromatic with long chains  Carotenoids are highly conjugated hydroxylated derivatives of 40-carbon hydrocarbons called carotenes.  They absorb visible light.  Most of the yellow and red pigments occurring naturally are carotenes.  In animals, β-carotene is metabolically converted to Vitamin A, which is necessary for visual activity.

BEHAVIOUR OF LIPIDS IN WATER  Lipids are insoluble in water normally existing in aqueous environment.  Many are amphiphilic or amphipathic – consisting of a non-polar hydrocarbon and a polar or ionic region or both.  When these amphipathic molecules are dispersed in water, their hydrophobic parts segregate from the solvent by self aggregation to form monolayers near the water- air boundary and micelles that are dispersed in water.  The tendency for hydrocarbon chains to become remote from the polar solvent, water, is known as the hydrophobic effect.  Vesicles and sheets may also arise due to attractive forces between hydrocarbon chains (van der Walls forces) caused by the hydrophobic effect or repulsive forces between the polar head groups. An isolated bilayer cannot exist as such in water, because exposed hydrocarbon tails would exist at the edges of the sheet

MEMBRANES  The cytoplasm of cells is surrounded by a plasma membrane, sub-cellular structures such as the nucleus, lysosomes, and mitochondria are delineated by membranes.  Membranes contain lipids, proteins, and a small amount of carbohydrate.  They exist as closed phospholipid bilayers and separate the cell from its environment, or separate different parts of the cell from each other thus allowing certain activities to occur independently.  Membranes, having appropriate selective permeabilities, can act as a physical barrier allowing space enclosed by it to acquire and exclude useful and harmful substances respectively.  Membranes also provide an environment for chemical reactions requiring nonaqueous conditions.

DISCUSSION- QUESTIONS 1. Why do differences in melting points exist between fatty acids containing the same number of carbon atoms? 2. Which of the following lipids are amphiphilic: fatty acid; acylate ions; TAGs; cholesterol; phosphosphingolipids; glycosphingolipids?

SUGGESTED ANSWER-1  The preferred conformation of a chain of saturated C atoms is a long, straight structure. A cis double bond will cause a bend in the structure, making it less likely to pack into a crystal than a saturated molecule of the same length. A trans double bond does not cause a bend in the chain.  Straight molecules can pack together more densely and give crystals of higher melting point than the m.pt. of bent molecules of the same size; more energy is required to separate molecules when they are heated

SUGGESTED ANSWER -2  Fatty acids, TAGs, cholesterol are not amphiphilic; they have a extremely weak polarity.  The rest possess at least one formal charge or an abundance of hydroxyl groups in one part of the molecule.