Lipids: Comprehensive Notes

Lipids

• Chemically diverse group of compounds containing multiple C-C and C-H bonds.
• Defining feature: Insoluble in water.
• Common functions:
  • Energy source
  • Chemical messenger
  • Structural elements of biological membranes
• Common types:
  • Storage lipids
  • Membrane lipids

Storage Lipids

• Includes triacylglycerols (TAGs).
• Triacylglycerols are composed of glycerol and fatty acids.

Fatty Acids

• Building blocks of lipids; carboxylic acids (RCOOH).
• Hydrocarbon chains ranging from 4 to 36 carbons, usually containing an even number of carbon atoms.
• May contain double bonds.

Fatty Acids Nomenclature

• Delta (Δ) system: Assigns number 1 to the carboxyl carbon and α to the carbon next to it. The position of double bonds is indicated by Δ followed by a superscript number indicating the lower-numbered carbon of the double bond.

• Omega (ω) system: Assigns number 1 to the methyl carbon at the other end of the chain. The positions of the double bonds are indicated relative to the ω carbon. Commonly used for polyunsaturated fatty acids.

• Example:

  • 18:2 Δ9,12 is equivalent to 18:2 ω-6

Common Fatty Acids

Melting Point of Fatty Acids

• ↑ Number of carbons → ↑ Attractive forces → ↑ Melting point.
• ↑ Unsaturation → ↓ Attractive forces → ↓ Melting point.
• Unsaturated fatty acids have double bonds generally in cis formation.
• Saturated fatty acids: No double bonds.
• Monounsaturated fatty acids (MUFA): One C-C double bond.
• Polyunsaturated fatty acids (PUFA): Multiple C-C double bonds.

Simple vs Compound Lipids

• Simple Lipids: TAGs and Waxes
• Compound Lipids: Glycolipids, Sulfolipids, and Phospholipids

Saponifiable Lipids

• Can be converted into smaller molecules by hydrolysis with water in the presence of an acid.
  • Triacylglycerols.
  • Waxes.
  • Phospholipids.

Lipid Reaction #1: Hydrolysis

• Triacylglycerols are hydrolyzed with water in the presence of acid, base, or enzymes (in the body).

Triacylglycerols (TAGs)

• Triglycerides are formed when a glycerol molecule is reacted with three fatty acids in a condensation reaction, forming three water molecules as a byproduct.

• Simple triacylglycerols: contain three identical saturated carbon chains

• Mixed triacylglycerols: contain one unsaturated carbon chain

Fats

• Higher melting point.
• Solid at room temperature.
• Derived from fatty acids having few double bonds.
• High percentage of saturated fatty acids.
• Animal origin.

Oils

• Lower melting point.
• Liquids at room temperature.
• Derived from fatty acids having a large number of double bonds.
• High percentage of unsaturated fatty acids.
• Vegetable origin.

Lipid Reaction #2: Saponification

• Soaps are metal salts of fatty acids prepared by alkaline/basic hydrolysis (saponification) of a triacylglycerol.

Waxes

• Esters (RCOOR’) formed from a fatty acid and a high molecular weight alcohol.
• Hydrophobic. Forms a protective coating.
• Functions:
  • Lubrication
  • Water-repellent
  • High melting point (Ranges from $60^\circ C$ to $100^\circ C$, generally higher than TAGs).
  • Energy storage (Typical metabolic fuel for free-floating microorganisms such as plankton).
• Secreted by skin glands to protect hair and skin.
• Present in leaf coating to prevent excessive evaporation.
• Widely used in manufacturing of lotion, ointments, and polishes.

Spermaceti Oil

• Found in sperm whales.
• Mixture of TAGs and waxes, keeps the melting temperature higher.

Structural Lipids

• Includes phospholipids, sphingolipids, and glycolipids.

Membrane Lipids

• Exhibit both hydrophilicity and hydrophobicity (Amphipathic).
• Synthesized from mixtures of long-chain and medium-chain fatty acids.
• Form biological membranes: double layer of lipids.

Phospholipids

• Lipids that contain a phosphate (PO4) group.
• Have another polar head group joined by phosphodiester linkage.
• Include glycerophospholipids and sphingomyelins.

Glycerophospholipids (Phosphoglycerides)

• Have a highly polar group (sometimes charged groups).
• Backbone is made of glycerol, a prochiral group.
• Ex: Lecithin molecule drawn as polar head and two nonpolar tails. Forms bilayer sheets, liposomes and micelles.

Sphingomyelins

• Present in the plasma membranes of animal cells and are especially prominent in myelin (membranous sheath that surrounds and insulates the axons of some neurons).

Glycolipids

• Occur largely in the outer face of plasma membranes whose head groups are made of sugars.
• Sphingolipids at cell surfaces are sites of biological recognition.

Glycosphingolipids

• Cerebrosides: Either galactose (neural tissues) or glucose (non-neural tissues).
• Globosides: With two or more sugars, usually D-glucose, D-galactose, or N-acetyl-D-galactosamine.
• Gangliosides: One or more residues of N-acetylneuraminic acid (Neu5Ac).

Galactolipids (Sulfolipids)

• Predominate in plant cells.
• One or two galactose residues are connected by a glycosidic linkage to glycerol.
• Localized in the thylakoid membranes (internal membranes) of chloroplasts.
• Make up 70% to 80% of the total membrane lipids of a vascular plant.

Non-Saponifiable Lipids

Cholesterol

• Major component of the cell membrane.
• Maintains structural integrity and fluidity.

Sterols

• Group of membrane lipids whose carbon skeletons contain several fused rings.

• Most sterols act as:

  1. Membrane component
  2. Emulsifier
  3. Messenger
  4. Cofactors

• Most prominent steroid.

• Synthesized in the liver and found in almost all body tissues.

• Obtained in the diet (meat, cheese, butter, and eggs).

• Plays pivotal roles in maintaining structural integrity and regulating the fluidity of cell membranes.

• Precursor to a wide variety of steroids.

• Lipoproteins - transporters of lipids, including cholesterol and TAGs, in the bloodstream.

Lipoproteins

• High-density lipoproteins (HDL): Lower amount of lipids, larger density (smaller size). Transport excess cholesterol in cells back to the liver.

• Low-density lipoproteins (LDL): Higher amount of lipids, smaller density (larger size). Transport cholesterol from the liver to the cells.

• Elevated LDL leads to elevated cholesterol levels in the bloodstream.

• Cholesterol is insoluble in the aqueous medium of blood which may lead to coronary artery disease and heart attack.

Factors that Elevate LDL

• Saturated fatty acids and trans fats elevate LDL, while unsaturated fatty acids lower LDL.

Trans Fats Formation

• Naturally, unsaturated fatty acids are in cis form.
• Trans fats are formed by partial hydrogenation of PUFA.
• Cooking oils that undergo partial hydrogenation improve shelf life and stability at high temperatures.

Lipid Reaction #3: Hydrogenation

• Process of adding hydrogen to unsaturated fatty-acid chains.
• Complete hydrogenation: All C-C double bonds are removed.
• Partial hydrogenation: Some of the fatty acid double bonds are converted into single bonds.

Lipids as Emulsifiers

• Bile acids: Polar derivatives of cholesterol that act as detergents in the intestine, emulsifying dietary fats to make them more readily accessible to digestive lipases.

Lipids as Messengers

• Eicosanoids: Biologically active compounds containing 20 carbon atoms derived from the fatty acid, arachidonic acid.
  • Act only on cells near the point of hormone synthesis instead of being transported in the blood to act on cells in other tissues or organs.
  • Involved in reproductive function, inflammation, fever, pain, blood clot formation, regulation of blood pressure, gastric acid secretion.

Prostaglandins

• Stimulate contraction of the smooth muscle of the uterus during menstruation and labor.
• Affect blood flow, wake-sleep cycle, and responsiveness of certain tissues to hormones.
• Elevate body temperature (fever) and cause inflammation and pain.

Thromboxanes

• Produced by platelets and act in the formation of blood clots and the reduction of blood flow to the site of a clot.
• NSAIDs: Nonsteroidal anti-inflammatory drugs; inhibit the enzyme that catalyzes the formation of prostaglandin and thromboxanes.

Leukotrienes

• Found in leukocytes and act as powerful biological signals.
• Leukotriene D4: Induces contraction of the smooth muscle lining the airways to the lung.
• Overproduction of leukotrienes causes asthmatic attacks; leukotriene synthesis is one target of anti-asthmatic drugs.

Lipids as Messengers: Hormones

• Steroid Hormones: synthesized in one part of an organism, which then elicits a response at a different site
  • Move through the bloodstream (on protein carriers) from their site of production to target tissues, where they enter cells, bind to highly specific receptor proteins in the nucleus, and trigger changes in gene expression and thus metabolism
  • Very low concentrations of hormones (nanomolar or less) are sufficient to produce responses in target tissues.

Classes

• Sex hormones: Produced by sex organs
• Adrenal cortical steroids: Produced by adrenal cortex

Male Sex Hormones

• Testosterone and androsterone
• Made in the testes and control the development of secondary sex characteristics in males

Female Sex Hormones

• Estrogen (e.g., Estrone and Estradiol) regulate the menstrual cycle and control development of secondary sex characteristics
• Progestin (e.g., progesterone) - pregnancy hormone responsible for the preparation of the uterus for implantation of a fertilized egg.

Anabolic Steroids

• synthetic androgen analogues that promote muscle growth
• Used by athletes and body builders (prolonged use can cause physical and psychological problems).

Adrenal Cortical Steroids

• Aldosterone (Mineralocorticoid):
  • regulate salt and water in the body.
  • Regulates blood pressure and volume by controlling the concentration of $Na^+$ and $K^+$ in body fluids.
• Cortisone and cortisol:
  • serve as anti-inflammatory agents and regulate carbohydrate metabolism - “Stress hormones”

Lipids as Cofactors: Vitamins

• Vitamins: Organic compounds required in small quantities for normal metabolism and must be obtained from the diet.

Fat-Soluble Vitamins

• A, D, E, K

• Synthesizes 1,25-dihydroxycholecalciferol, which regulates calcium uptake in the intestine and calcium levels in kidney and bone.
• Vitamin D deficiency causes rickets (bone malformation).

• Retinoic acid regulates gene expression in the development of epithelial tissue, including skin
• Retinal, is the pigment that initiates the response of rod and cone cells of the retina to light, producing a neuronal signal to the brain
• Vitamin A deficiency causes night blindness and dry eyes and skin.

• Biological antioxidants (aromatic ring present)
• Laboratory animals fed diets depleted of vitamin E develop scaly skin, muscular weakness and wasting, and sterility

• Phylloquinone regulates the synthesis of clotting proteins (prothrombin).
• Deficiency of Vitamin K leads to excessive or fatal bleeding