02

LIPIDS

Introductory Biochemistry

• Lipids are essential components of all living organisms.

• They are defined as water insoluble organic compounds.

• Lipids can be classified as:

  • Hydrophobic (nonpolar)

  • Amphipathic (containing both nonpolar and polar regions)

Functions of Lipids

The biological functions of lipids are as diverse as their chemistry:

1. Structural components of biological membranes.

2. Storage and transport forms of metabolic fuel.

3. Protective coating on the surface of many organisms.

4. Cell surface components concerned in cell recognition, species specificity, and tissue immunity.

5. Insulation barriers.

6. Some vitamins and hormones.

7. Precursors of other important substances.

Structural Relationship of Major Lipid Classes

• Eicosanoids

• Fatty acids

• Triacylglycerols

• Waxes

• Sphingolipids

• Glycerophospholipids

• Plasmalogens

• Examples of glycerophospholipids include:

  • Phosphatidates

  • Phosphatidylethanolamines

  • Phosphatidylserines

  • Phosphatidylcholines

  • Phosphatidylinositols

• Steroids

• Lipid vitamins

• Terpenes

• Isoprenoids

• Cerebrosides

• Gangliosides

• Other glycosphingolipids

FATTY ACIDS

Structure and Nomenclature

• A fatty acid (FA) is defined as a long chain aliphatic carboxylic acid.

• All FAs possess:

  • A long hydrocarbon chain

  • A terminal –COOH (carboxylic acid) group.

• FAs differ from one another based on:

  1. Length of the hydrocarbon tails.

  2. Degree of unsaturation (number of double bonds).

  3. Position of the double bonds in the chain.

Characteristics of Fatty Acids

• Fatty acids can contain between 4 to 30 carbon atoms.

• The most abundant fatty acids typically have 12 to 20 carbons, with those of 16 to 18 predominating.

• Odd-numbered fatty acids are found in trace amounts in terrestrial animals and are more abundant in marine organisms.

• The IUPAC nomenclature states that the carboxyl carbon is designated as C-1.

• In common nomenclature, designations follow as α, β, γ, δ, ε, etc. from C-1 forward.

• The carbon farthest from the carboxyl group is termed omega (ω).

Common Fatty Acids Characteristics

• Common Fatty Acids include:

  1. Laurate

  • IUPAC name: Dodecanoate

  • Melting point: 44 °C

  • Molecular formula: $CH<em>3(CH</em>2)_{10}COO$

  1. Myristate

  • IUPAC name: Tetradecanoate

  • Melting point: 0 °C

  • Molecular formula: $CH<em>3(CH</em>2)_{12}COO$

  1. Palmitate

  • IUPAC name: Hexadecanoate

  • Melting point: 63 °C

  • Molecular formula: $CH<em>3(CH</em>2)_{14}COO$

  1. Stearate

  • IUPAC name: Octadecanoate

  • Melting point: 70 °C

  • Molecular formula: $CH<em>3(CH</em>2)_{16}COO$

  1. Arachidate

  • IUPAC name: Eicosanoate

  • Melting point: 75 °C

  • Molecular formula: $CH<em>3(CH</em>2)_{18}COO$

  1. Behenate

  • IUPAC name: Docosanoate

  • Melting point: 81 °C

  • Molecular formula: $CH<em>3(CH</em>2)_{20}COO$

  1. Lignocerate

  • IUPAC name: Tetracosanoate

  • Melting point: 84 °C

  • Molecular formula: $CH<em>3(CH</em>2)_{22}COO$

Unsaturation and Melting Point

• Unsaturated fatty acids predominate over saturated fatty acids, particularly in higher plants and animals that live at lower temperatures.

• The melting points of fatty acids are influenced by:

  • The chain length

  • The degree of unsaturation

• Monounsaturated fatty acids are referred to as monoenoic, while polyunsaturated fatty acids are termed polyenoic.

• In most polyenoic fatty acids, one double bond is located between carbons C9 and C10. Additional double bonds occur toward the methyl-terminal end of the chain.

• Double bonds are generally found in the cis configuration.

• In most polyunsaturated fatty acids, the double bonds are separated by a methylene group (i.e., they are not conjugated).

Structures of C18 Fatty Acids

• Examples of three common C18 fatty acids include:

  1. Linolenate 18:3(Δ9,12,15)

  2. Oleate 18:1(Δ9)

  3. Stearate 18:0

• The position of double bonds is indicated using the delta (Δ) notation, where the number represents the lower-numbered carbon of each pair of double bonds.

• Shorthand notation example: 20:4Δ5,8,11,14 (total number of carbons : number of double bonds, Δ double bond positions).

WORKING WITH LIPIDS

Gas Liquid Chromatography

• Gas liquid chromatography is used for analyzing mixtures of fatty acids.

• This method separates volatile compounds of a mixture based on their different solubilities in the stationary liquid phase.

• The mobile phase used is an inert gas (e.g., argon), while the stationary phase consists of a small amount of liquid packed within the chromatography column, which is constructed from a coiled tube.

Process of Gas Liquid Chromatography

1. The fatty acids are first converted into methyl esters to improve volatility.

2. The ester mixture is then injected into the heated column.

3. The sample is vaporized and mixes with the inert gas.

4. The gas mixture then moves through the column under pressure, eventually emerging into a detection device that records the presence and amount of substances as they are eluted.

Representation of Gas Liquid Chromatography

• A typical separation of volatile methyl esters of fatty acids can be represented visually.

TRIACYGLYCEROLS

Structure

• Triacylglycerols (TGs) are composed of three fatty acyl residues esterified to a glycerol molecule (a 3-carbon sugar alcohol).

• A simple triacylglycerol contains the same fatty acid at all three positions (e.g., triolein, the principal TG in olive oil, has 3 oleic acid residues).

• Most naturally occurring TGs are considered mixed, with different fatty acids at various positions.

Energy Storage and Insulation

• Triacylglycerols are the most abundant family of lipids, also known as triglycerides.

• They are characterized by their hydrophobic nature, being stored in cells in an anhydrous form (e.g., fat droplets in adipocytes and oils in the seeds of various plants).

• TGs serve as critical metabolic fuels, providing 2 to 3 times more energy than proteins or carbohydrates.

• They also offer physical protection and thermal insulation for various body organs.

• TGs that are solid at room temperature are termed fats, whereas those that are liquid are termed oils.

GLYCEROPHOSPHOLIPIDS

Membrane Lipids

• Glycerophospholipids are the most abundant lipids found within membranes. They are also referred to as phosphoacylglycerols or phosphoglycerides.

• They possess a glycerol-3-phosphate backbone.

• The hydroxyl group at C-3 on glycerol is esterified to phosphoric acid, while the other two -OH groups are esterified to fatty acids, forming phosphatidates.

Characteristics of Phosphoglycerides

• Phosphoglycerides contain a polar head group, denoted as X-OH, where the -OH is esterified to the phosphoric acid.

• They are amphipathic or polar lipids that differ in their size, shape, and electric charge based on their polar head group.

• Each type of phospholipid can exist in various species, differing based on their fatty acid substituents.

• Typically, one saturated fatty acid is esterified to C-1 and one unsaturated fatty acid to C-2 of glycerol-3-phosphate.

Examples of Phosphoglycerides

• Examples of polar heads (hydrophilic) include:

  • Phosphatidylethanolamine

  • Phosphatidylserine

  • Phosphatidylcholine

Plasmalogens

• Plasmalogens possess ether-linked fatty acids.

• The C-1 hydrocarbon substituent is attached via a vinyl ether linkage (not an ester linkage).

• Ethanolamine and choline are often esterified to the phosphate group in plasmalogens.

• They account for 23% of glycerophospholipids in the human central nervous system and are also present in peripheral nerve and muscle tissues.

Phospholipases

• Phospholipases are enzymes utilized to dissect glycerophospholipid structures.

• Phospholipase A2 is the predominant phospholipase found in pancreatic juice, as well as in snake, bee, and wasp venom.

SHINGOLIPIDS

Membrane Lipids

• Sphingolipids are crucial membrane components in both plant and animal cells, particularly abundant in mammalian central nervous system (CNS) tissues.

• Sphingosine (trans-4-sphingenine) serves as the structural backbone.

• Ceramides consist of a fatty acyl group linked to C-2 of sphingosine by an amide bond; these are precursors to all sphingolipids.

Types of Sphingolipids

• Three major types of sphingolipids are identified:

  1. Sphingomyelins: phosphocholine or phosphoethanolamine is esterified to C-1 of ceramide.

  2. Neutral Glycosphingolipids: contain one or more neutral sugar residues linked via glycosidic bonds to C-1 of ceramide; cerebrosides are the simplest form.

  3. Acidic Glycosphingolipids: possess oligosaccharide chains with N-acetyl-neuraminic acid (NeuNAc or sialic acid) linked to C-1 of ceramide; these are known as gangliosides.

Sphingomyelins

• Sphingomyelins are classified as phospholipids and are found in the plasma membranes of many mammalian cells.

• They are essential components of myelin sheaths surrounding specific nerve cells.

Cerebrosides

• Cerebrosides are the simplest neutral glycosphingolipids, containing a monosaccharide (galactose or glucose) bound by a β-glycosidic bond to the –OH of C-1 of ceramide.

• Galactocerebrosides are prevalent in nerve tissues, accounting for roughly 15% of lipids in myelin sheaths.

Gangliosides

• Gangliosides represent the most complex group of sphingolipids, characterized by an oligosaccharide component that contains at least one sialic acid residue.

• The specific structure of the oligosaccharide identifies each ganglioside (e.g., GM1, GM2, GM3, etc.), with 'M' indicating monosialo.

• They are significant components of cell surface membranes, making up about 6% of brain lipids.

• Gangliosides are vital for cell-cell recognition and influence growth and differentiation of tissues.

• They serve as cell surface receptors for bacterial toxins (e.g., cholera toxin).

• Disorders associated with ganglioside metabolism, like Tay-Sachs disease, arise from issues with ganglioside breakdown, leading to severe health consequences.

Glycolipids

• Gangliosides and cerebrosides are categorized as glycolipids due to their carbohydrate content.

• They provide antigenic markers to cells, influencing interactions with hormones, viruses, and bacterial toxins.

WAXES

• Waxes are defined as nonpolar esters formed from long-chain fatty acids and long-chain alcohols or sterols.

• Example: Myricyl palmitate is a major component of beeswax, characterized by high water insolubility and a high melting point.

• Waxes serve as protective waterproof coatings on leaves, fruits, fur, feathers, and exoskeletons of insects.

Ear Wax

• Commonly known as cerumen, ear wax is secreted by cells lining the auditory canal.

• It serves to lubricate the canal and trap particles to protect the ear drum.

• The composition includes long-chain fatty acids, cholesterol, ceramides, squalene, triacylglycerols, and true waxes (approximately 10% of weight).

ISOPRENOIDS

Terpenes

• Terpenes are constructed from multiples of the five-carbon isoprene unit and can be linear or cyclic compounds.

• Terpenes are abundant in plants and often exhibit characteristic odors/flavors.

• They are intermediates in steroid biosynthesis, with lipid vitamins (A, D, E, and K) being isoprenoid derivatives.

• Terpenes can undergo extensive modifications to form terpenoids (e.g., gibberellin).

Types of Terpenes

1. Monoterpenes: Examples include menthol (from mint oil) and camphor (from camphor oil).

2. Diterpenes: Example includes phytol, a component of chlorophyll.

3. Triterpenes: Example includes squalene, a significant precursor in cholesterol synthesis.

4. Tetraterpenes: Carotenoids, like β-carotene, a precursor of vitamin A.

5. Polyterpenes: Example includes natural rubber.

Steroids

• Steroids are derivatives of a saturated tetracyclic hydrocarbon known as perhydrocyclopentanophenanthrene, which consists of four fused ring systems: three six-carbon rings (A, B, C) and one five-carbon ring (D).

• The structure of steroids is nearly planar.

• Cholesterol is the most abundant steroid in animals, recognized as a sterol having a hydroxyl group at C-3, and an aliphatic side chain of eight carbons at C-17.

• Cholesterol modulates the fluidity of mammalian cell membranes and is vital for membrane properties.

• It is an essential precursor for:

  1. Steroid hormones: These hormones regulate multiple physiological functions, including sexual development (testosterone and progesterone) and carbohydrate metabolism.

  2. Bile salts: These are detergent-like compounds that facilitate the emulsification and absorption of lipids in the intestines.

Others

• Plants generally have low cholesterol levels; stigmasterol and β-sitosterol are common sterols in their membranes.

• Yeast and fungi contain alternative sterol forms such as ergosterol.

• Most prokaryotes (with exceptions like mycoplasms) contain minimal to no sterols.

Cholesteryl Esters

• Cholesterol can be converted into cholesteryl esters for cell storage or transport in the blood.

• Cholesteryl esters are more hydrophobic than cholesterol due to the esterification of C-3 hydroxyl with a fatty acid.

• They are transported in blood plasma within lipoproteins.

EICOSANOIDS

• Eicosanoids are defined as oxygenated derivatives of C20 polyunsaturated fatty acids (for example, arachidonic acid, $20:4 riangle 5,8,11,14$).

• Nearly all mammalian cells, except red blood cells (RBCs), produce eicosanoids.

• Aspirin irreversibly inhibits cyclooxygenases, thereby alleviating pain, fever, and inflammation by halting the synthesis of prostaglandins.

Types of Eicosanoids

1. Prostaglandins: Characterized by a cyclopentane ring. Prostaglandin E2 is known to induce constriction of blood vessels.

2. Thromboxanes: Recognized for having a six-carbon ring with an ether; Thromboxane A2 plays a role in blood clot formation.

3. Leukotrienes: Composed of three conjugated double bonds, with Leukotriene D4 acting as a mediator for smooth muscle contraction and bronchial constriction in asthmatic conditions.

Functions of Eicosanoids

• Eicosanoids function as local regulators and act like hormones at low concentrations. They are involved in:

  • The inflammatory response (e.g., arthritis, psoriasis).

  • The production of pain and fever.

  • The induction of labor.

  • The regulation of sleep/wake cycles.

  • The control of blood pressure and blood clot formation.

LIPOPROTEINS

Overview

• Certain lipids associate with specific proteins, forming lipoprotein systems, categorized into two major types:

  • Transport lipoproteins

  • Membrane systems

• In these systems, lipids and proteins are held together by hydrophobic interactions between the non-polar surfaces of lipids and proteins.

• Lipoproteins function as transport vehicles in blood plasma, as triglycerides, cholesterol, and cholesteryl esters are insoluble in water, preventing transport as free molecules.

Classification of Lipoproteins

• Plasma lipoproteins are classified into five broad categories based on their functional and physical properties:

  • Chylomicrons

  • Very Low-Density Lipoproteins (VLDLs)

  • Intermediate Density Lipoproteins (IDLs)

  • Low-Density Lipoproteins (LDLs)

  • High-Density Lipoproteins (HDLs)

Characteristics of Plasma Lipoproteins

• Plasma lipoproteins form globular micelle-like particles comprising:

  • A hydrophobic core of triglycerides and cholesteryl esters.

  • A hydrophilic surface formed by an amphiphilic coating of proteins, phospholipids, and cholesterol.

Properties of Lipoproteins

• Five categories of human plasma lipoproteins have varying molecular weights, densities, and chemical compositions.