Week 8 - Lipids

Intro + Classification

• Biomolecules characterized as insoluble or sparingly soluble in water , extractable by organic solvents such as diethyl ether, chloroform, and carbon tetrachloride.

• Physical properties reflect hydrophobic nature of their structures due to being readily soluble in organic solvents.

• Lipids are classified by solubility and their hydrolysis products:

  1. Triacylglycerol (triglycerides): main storage lipid

  2. Phospholipids: main constituent of membrane

  3. Sphingolipids: functions in cell recognition

  4. Glycolipids

  5. Waxes

  6. Terpenes

  7. Steroids

 

• Classification based on structure and function:

  1. Lipids that do not contain fatty acids (e.g., cholesterol, terpenes).

  2. Lipids that contain fatty acids (complex lipids), which are further separated into storage lipids and membrane lipids.

Biological function

• Cofactors for enzymes:

  • Vitamin K: blood clot formation.

  • Coenzyme Q: ATP synthesis in mitochondria.

• Signaling molecules:

  • Paracrine hormones (act locally).

  • Steroid hormones (act body-wide).

  • Growth factors.

  • Vitamins A and D (hormone precursors).

• Pigments: color of tomatoes, carrots, pumpkins, and some birds.

• Antioxidants: Vitamin E.

Triaglycerols

• Form of majority of fatty acids in biological systems

• Primary storage form of lipids (body fat).

• Physical states:

  • Solid triacylglycerols = fats.

  • Liquid triacylglycerols = oils.

• Less soluble in water than fatty acids due to the lack of a charged carboxylate group.

• Less dense than water, causing fats and oils to float.

• Plant triacylglycerols:

  • Low MP + are liquids at room temp due to large proportion of unsaturated fatty acids (e.g., oleic, linoleic, or linolenic acids).

• Animal triacylglycerols:

  • have higher proportion of saturated fatty acids (e.g., palmitic, stearic acids) —> higher MP + semi-solid/solid states at room temp.

• Structure and Nomenclature:

  • Neutral fats with a general structure containing three fatty acids bonded by ester linkages to a glycerol molecule.

Fatty Acids

• Carboxylic acids with hydrocarbon chains containing between 4 to 36 carbons.

• Saturation classes:

  1. Saturated: no double bonds between carbons in the chain.

  2. Monounsaturated: one double bond between carbons in the alkyl chain.

  3. Polyunsaturated: more than one double bond in the alkyl chain.

• Structural features:

  • Double bonds in unsaturated fatty acids produce spatial isomerism (cis or trans isomers).

  • Occur mainly in nature as esters (triacylglycerols and phospholipids) and very rarely as free fatty acids.

• Nomenclature systems:

  • Carbon atoms are numbered or lettered from the carboxyl group or from the carbon atom farthest removed from the carboxyl group (n or ω numbering system).

  • Greek letters: α-carbon is adjacent to the carboxyl group, and ω-carbon is farthest away.

Physical Properties + Conformation

• Conformation:

  • Saturated chains usually have adopt straight + linear conformations.

  • Double bonds in natural unsaturated fatty acids are commonly in cis configuration —> kinks the chain.

• Solubility:

  • Decreases as chain length increases.

• Melting Point:

  • Decreases as chain length decreases.

  • Decreases as the number of double bonds increases.

• Packing efficiency:

  • Saturated fatty acids pack in an orderly way = extensive favorable interactions.

  • Unsaturated cis fatty acids pack less orderly due to the kink = less-extensive favorable interactions.

  • Takes less thermal energy to disrupt disordered packing, giving unsaturated cis fatty acids a lower MP.

Synthetic Detergents

• Detergent refers to any cleansing agent (including soaps); synthetic detergents = syndets.

• Syndets do not form precipitates with ions in hard water.

• Classification of Detergents:

  1. Anionic Detergents: sulfates on fatty acids or sulfonate salts of hydrocarbons.

  2. Cationic Detergents: referred to as invert soap because the water-soluble end carries a positive charge; possesses germicidal properties.

  3. Non-ionic Detergents: contain polar covalent structures providing water solubility; used extensively in dishwashing liquids.

Halogenation

• Unsaturated fatty acids (free or as esters in fats/oils) react with halogens by addition at the double bond.

• When halogens add across the carbon-carbon double bonds of Unsaturated fatty acids (free or as esters in fats/oils)

• Reaction = decolourization of the halogen solution.

• Degree of absorption is proportional to the number of double bonds, serving as an index to the degree of unsaturation.

• Iodine number:

  • the mass of iodine in grams that is absorbed by 100 grams of a chemical substance, fat, or oil

  • High iodine number = high degree of unsaturation.

Rancidity

• any fat or oil that develops a disagreeable odour.

• Responsible chemical reactions:

  1. Hydrolysis: under moist and warm conditions, ester linkages hydrolyze, liberating volatile acids.

  2. Oxidation: occurs in triacylglycerols containing polyunsaturated fatty acids; initiated by free radical formation followed by production of hydroperoxides.

• Suppression:

  • Commonly used antioxidants include ascorbic acid (Vitamin C), tocopherol (Vitamin E), and BHT (butylated hydroxytoluene).

Hydrogenation

Process of converting vegetable oils into solid fats (also referred to as hardening).

Eicosanoids (Arachidonic Acid Derivatives)

• Enzymatic oxidation of arachidonic acid yields signaling lipids:

  1. Prostaglandins:

     • Family of complex unsaturated 20-carbon fatty acids containing a 5-membered ring.

     • Act as autocrine regulators (modulate hormone effects).

     • Functions: control blood pressure, uterine contractions, relieve nasal congestion, asthma, and rheumatoid arthritis.

     • Highest concentration in seminal fluid; widely distributed in kidney, pancreas, lung, brain, and blood.

  2. Leukotrienes:

     • Derived from arachidonic acid, found in leukocytes, contain a triene (three conjugated double bonds).

     • LTC4, LTD4, and LTE4 are components of slow-reacting substance of anaphylaxis (SRS-A).

     • Effects: vasoconstriction, bronchoconstriction, oedema, chemotactic agent, increase fluid leakage during inflammation.

  3. Thromboxane:

     • Derivatives of arachidonic acid or eicosatetraenoic acid (EPA); contain a cyclic ether.

     • TXA2 and TXB2 are produced primarily by platelets.

     • TXB3 is synthesised from EPA by polymorphonuclear leukocytes; plays a role in platelet aggregation and vasoconstriction following tissue injury.

Phospholipids (Phosphoglycerides)

• Basic structure: A glycerol backbone with a phosphate ester group attached (derivatives of phosphatidic acid).

• A polar alcohol (R-OH) is bonded by an ester linkage to C-3 phosphate.

• Structural configuration: polar head and two non-polar tails (amphipathic property critical for membrane structure).

• Occur almost exclusively in cellular membranes of plants and animals.

Sphingolipids + Sphingomyelin

• Sphingolipids:

  • Backbone = a long-chain amino alcohol called sphingosine (NOT glycerol).

  • Fatty acid joined via amide linkage.

  • Polar head group connected by glycosidic or phosphodiester linkage.

  • Found in plants and animals; present in large amounts in nerve and brain tissue.

  • Glycosphingolipids found largely on outer face of plasma membranes.

• Sphingomyelin:

  • Structure: Ceramide (sphingosine + amide-linked fatty acid) + phosphocholine attached to alcohol.

  • Only sphingosine-derived phospholipid in membranes.

  • Abundant in myelin sheath surrounding nerve cells.

  • Multiple sclerosis (MS): neurological disease where nerve fibres slowly lose insulating myelin sheaths.

Glycolipids + Membrane Lipid Turnover Defects

• Glycolipids:

  • Lipids containing a polar carbohydrate head (e.g., D-glucose or D-galactose) but no phosphate group.

  • Derived from glycerol or sphingosine

  • Cerebrosides (sphingosine) are found in brain/nervous system membranes and abundant in myelin sheath.

  • Characterized by polar carbohydrate head and two non-polar tails.

• Diseases from turnover defects:

  • turnover of membrane lipids lead to diseases: Generalized gangliosidosis, Tay-Sachs disease, Sandhoff's disease, Fabry's disease, Gaucher's disease, and Niemann-Pick disease

Waxes:

• Definition: Esters of long-chain saturated and unsaturated fatty acids with long-chain alcohols.

• Physical Properties: Insoluble in water and have high melting points.

• Biological Functions:

  • Storage of metabolic fuel in plankton.

  • Protection and pliability for hair and skin in vertebrates.

  • Waterproofing of feathers in birds.

  • Protection from evaporation in tropical plants and ivy.

  • Used in lotions, ointments, and polishes.

• Types, Sources, and Uses:

  • Beeswax: Source = Honey Comb; Use = Dental impressions.

  • Carnauba wax: Source = Palm leaves; Use = Floor wax, furniture polish.

  • Cerumen: Source = Ear Wax; Use = Protects inner ear.

  • Lanolin: Source = Wool (sheep); Use = Base for ointments and creams.

  • Spermaceti: Source = Sperm Whale; Use = Cosmetics, candles.

Terpenes

• Compounds all derived from a isoprenoid unit (simple repeating unit)

• Class includes rubber, carotenoids, steroids, and simple terpenes.

• Key Terpene Products:

  • Carotene: Essential dietary vitamin A compound.

  • Squalene: Precursor intermediate of sterol and steroid hormones.

Sterols + Cholestrol

• Sterol Structure:

  • Steroid nucleus: Four fused carbon rings.

  • Hydroxyl group (polar head) located in the A-ring.

  • Contains various nonpolar side chains.

  • The steroid nucleus is almost planar.

Sterol Physiological Role

• Membrane Presence: Cholesterol and related sterols are present in the membranes of most eukaryotic cells, where they modulate fluidity and permeability and thicken the plasma membrane (most bacteria lack sterols).

• Source: Mammals obtain cholesterol from food or synthesize it de novo in the liver.

• Transport: Transported through blood vessels bound to proteins; cholesterol in low-density lipoproteins tends to deposit and clog arteries.

• Solubility: Insoluble in water, but soluble in most fat solvents.

• Importance: Cholesterol is the most important sterol found in animals.

• Hormone Precursor: Many hormones are derivatives of sterols.

• Bile Salts: Serve as emulsifying and solubilising agents to aid the intestinal hydrolysis of neutral fats.

Steroid Hormone + Drugs

• Characteristics:

  • Oxidized derivatives of sterols containing the sterol nucleus, but lacking the alkyl chain found in cholesterol.

  • More polar than cholesterol.

  • Synthesized from cholesterol in the gonads and adrenal glands.

  • Carried through the body in the bloodstream, usually attached to carrier proteins,.

  • Include male and female sex hormones.

Vitamins

• Cannot be synthesized by humans and must be obtained through dietary intake.

• Classes:

  • Fat-soluble vitamins: A, D, E, and K.

  • Water-soluble vitamins.

Vitamin E

• Function: a biological antioxidant protecting unsaturated fatty acids from oxidative damage.

Vitamin K

• Involved in forming prothrombin, which plays an essential role in blood clotting.

Vitamin D

• Synthesis & Metabolism:

  • Vitamin D3 (cholecalciferol) is formed within the skin from 7-dehydrocholesterol via a photochemical reaction.

  • Enzymatically converted to (calcitriol).

• Function: Calcitriol functions as a hormone regulating calcium uptake in the intestines and calcium levels in the kidneys and bone + regulating gene expression,.

• Deficiency: Leads to defective bone formation and rickets.

• Cure: Supplementation with vitamin D or vitamin D2.

Vitamin A

• Functions: Involved in processes of development, cell growth, differentiation, and vision.

• Metabolism:

  • Vitamin A1 (all-trans-retinol) or β-carotene obtained through diet.

  • Both can be enzymatically converted to all-trans-retinoic acid.

  • Retinoid hormone acts through nuclear receptors to regulate gene expression in embryonic development, stem cell differentiation, and cell proliferation,.

• Storage: Can be stored in the body.

• Dietary Sources: Fish liver oils, eggs, whole milk, butter, yellow vegetables.

• Deficiency:

  • In pregnancy: Congenital malformations and growth retardation.

  • In adults: Dryness of skin, eyes, and mucous membranes, and night blindness.

Natural Products used on Medicine

• Polyketides: Lipids produced via distinct biosynthetic pathways.

• Function as secondary metabolites (not central to metabolic pathways, but possess subsidiary functions),.

Biological Membranes

• Structure hold organelles together.

• Abilities: Recognize hormones and chemical stimulants; control the flow of information and materials into and out of the cell.

• Composition: Composed of both lipids and proteins.

• Phospholipids and glycolipids mixed with water form a lipid bilayer.

• No covalent bonds hold neighboring lipid molecules together; held by hydrophobic and hydrophilic interactions,.

• Membrane Proteins:

  • Control what enters and leaves the cell.

  • Form gates, pumps, enzymes, energy converters, and receptors.

Bilayer Lipid Membrane

• High content of unsaturated fatty acids in membrane lipids is a biologically important feature.

• Conformations:

  • Saturated fatty acids: Exist in extended forms requiring the least amount of energy to maintain.

  • Unsaturated fatty acids: Have a ~30° bend in the hydrocarbon chain per cis double bond,.

  • Two or more cis double bonds create additional bends.