Bettelheim, Brown, Campbell and Farrell Chapter 21 Lipids Bettelheim, Brown, Campbell and Farrell Chapter 21

Lipids Lipids: a heterogeneous class of naturally occurring organic compounds classified together on the basis of common solubility properties insoluble in water, but soluble in organic solvents including diethyl ether, dichloromethane, and acetone

Functional Classification of Lipids Storage of energy in animals Membrane components Lipid bilayer Messengers Primary: Hormones Secondary: mediate hormonal response prostaglandins, thromboxanes, etc.

Lipids Lipids include fatty acids, triacylglycerols, sphingolipids, phosphoacylglycerols, and glycolipids lipid-soluble vitamins prostaglandins, leukotrienes, and thromboxanes cholesterol, steroid hormones, and bile acids

Structural Classification of Lipids Simple Lipids Fatty acids, waxes Complex Lipids Multiple components Steroids Prostaglandins, Thromboxanes and Leukotrienes

Fatty Acids Fatty acid: an unbranched-chain carboxylic acid derived from hydrolysis of animal fats, vegetable oils, or membrane phospholipids Usually unbranched chain with 10-20 carbons EVEN number of carbons May be saturated or unsaturated (C=C) Unsaturated generally have cis double bonds Unsaturated fatty acids have lower melting points than their saturated fatty acids Most abundant are palmitic acid (16:0), stearic acid (18:0), and oleic acid (18:1)

Fatty Acid Notation (18:0) = 18 C and no double bonds (18:1) = 18 C and one double bond (18:3) = 18 C and three double bonds

Table 20.1, p.496

Fatty Acids

Waxes High molecular-weight esters 46 C total for triacontyl palmitate

Fats and Oils Contain glycerol and fatty acids Glycerol is triol Combined with ester bonds

Triglycerides Triglyceride (triacylglyceride): an ester of glycerol with three fatty acids

Example of triglyceride

Triglycerides Triglyceride (triacylglyceride): an ester of glycerol with three fatty acids

Triglycerides Physical properties depend on the fatty acid components More carbons: higher melting point More saturated (fewer C=C): higher melting point Oils: More unsaturated fatty acids Liquid at room temperature Fats: Primarily saturated fatty acids Semisolids or solids at room temperature

Triglycerides Melting points related to 3-D shape of triglyceride Saturated fatty acids can pack closely together More London dispersion forces between chains Higher melting points (above room temperature) Unsaturated fatty acids have cis double bonds Bend in chain prevents close packing Fewer London dispersion forces between them Lower melting points (below room temperature)

Packing of Saturated vs Unsaturated Fatty Acids

Hydrogenation Can convert liquid oil to solid fat by adding H2 to double bonds by using H2/catalyst Can control hardening to produce fats of a desired consistency Examples: Crisco, Spry, Dexo, etc. Margarine produced by partial hydrogenation of polyunsaturated oils derived from corn, cottonseed, peanut, and soybean oils

Hydrogenation of triglyceride

Iodine or Bromine Test for Unsaturation Add Br2 (or I2) to C=C. The more Br2 or I2 you add, the greater the number of double bonds in the fat or oil Iodine number is a measure of unsaturation.

Soaps Natural soaps are prepared by boiling lard or other animal fat with NaOH, in a reaction called saponification (Latin, sapo, soap)

Soaps Soaps clean by acting as emulsifying agents their long hydrophobic hydrocarbon chains cluster so as to minimize their contact with water their polar hydrophilic carboxylate groups remain in contact with the surrounding water molecules driven by these two forces, soap molecules spontaneously cluster into micelles

Soaps Soaps form water-insoluble salts (scum) when used in water containing Ca2+, Mg2+, and Fe3+ ions (hard water)

Complex Lipids Phospholipids Glycolipids contain an alcohol, two fatty acids, and a phosphate ester in glycerophospholipids, the alcohol is glycerol in sphingolipids, the alcohol is sphingosine Glycolipids complex lipids that contain a carbohydrate

Fig 20.1, p.501

Complex Lipids

Membranes Complex lipids form the membranes around cells and small structures within cells In aqueous solution, complex lipids form into a lipid bilayer, with a back-to-back arrangement of lipid monolayers polar head groups are hydrophilic and point to aqueous environment nonpolar tails are hydrophobic and are inside the bilayer hydrophobic interactions drive bilayer formation Rigidity of membrane depends on whether fatty acid tails are saturated or unsaturated

Membrane bilayer Hydrophilic head outside Hydrophobic tails inside

Membrane Rigidity Depends on nature of fatty acid tails Saturated fatty acids = more rigid Unsaturated fatty acids = less rigid Reindeer legs Near foot membranes have different fatty acid composition than in other parts of animal

Fig 20.1, p.501

Membrane bilayer Hydrophilic head outside Hydrophobic tails inside

Fluid Mosaic Model

Transport across membrane Passive transport Gap junctions—6 proteins make a central pore Small molecules pass through pores Ions, sugars, amino acids, nucleotides Large molecules can’t pass through Pore can be open or twisted shut Facilitated transport Interaction between transporter and transported molecule Active transport— Ions transported against concentration gradient Energy expended to change shape of protein and transport ion across membrane

Transport across membranes Active transport— Ions transported against concentration gradient Energy expended to change shape of protein and transport ion across membrane Polar compounds transported via specific transmembrane channels.

Complex lipids found in membranes Simple lipids Fig 20.1, p.501

Glycerophospholipids Glycerophospholipids (phosphoglycerides) are the second most abundant group of naturally occurring lipids found in plant and animal membranes, which consist of 40% -50% phosphoacylglycerols and 50% - 60% proteins Major phosphoacylglycerols are derived from phosphatidic acid glycerol + 2 fatty acids + phosphate Most abundant fatty acids in phosphatidic acids are palmitic (16:0), stearic (18:0), and oleic (18:1)

Glycerophospholipids A phosphatidic acid Fatty acid attached to C-2 is always unsaturated Can also add small alcohol to the phosphate to make a glycerophospholipid

Glycerophospholipids

Glycerophospholipids a lecithin

Glycerophospholipids Phosphatic acid Glycerol, 2 fatty acids, phosphate Lecithins Glycerol, 2 fatty acids, phosphate, choline Cephalins Glycerol, 2 fatty acids, phosphate, ethanolamine or serine

Sphingolipids Found in the myelin sheath of nerve axons Sphingomyelin deterioration found in MS Contain sphingosine, a long-chain aminoalcohol

Glycolipids Glycolipid: complex lipid that contains a sugar Sugar is glucose or galactose Cerebrosides found in brain and nerve synapses

Steroids Steroids: a group of plant and animal lipids that have a steroid ring structure

Cholesterol Cholesterol is the most abundant steroid in the human body, and also the most important Component in animal plasma membranes Precursor of all steroid hormones and bile acids

Lipoproteins Schematic of a low-density lipoprotein

Lipoproteins Cholesterol, along with fats, are transported by lipoproteins

Lipoproteins Protein has a higher density than lipids do HDL (high density lipoprotein) Have higher protein to lipid ratio LDL (low density lipoprotein) have lower protein to lipid ratio

Cholesterol Transport— from liver to peripheral cells Transport from the liver starts with VLDL (55 nm) Carried in plasma Density increases as fat is removed VLDL becomes LDL (22 nm) LDL stays in the plasma for about 2.5 days LDL carries cholesterol to cells, where specific LDL receptors (coated pits) bind it LDL is taken into cells where enzymes liberate free cholesterol and cholesteryl esters

Cholesterol Transport— from peripheral cells to liver HDL transport cholesterol from peripheral tissues to the liver and also transfer cholesterol to LDL Free cholesterol in HDL is converted to cholesteryl esters (while in serum) HDL binds to the liver cell surface and transfers its cholesteryl esters to the cell Cholesterol esters are used for the synthesis of steroid hormones and bile acids after HDL has delivered its cholesteryl esters to liver cells, it reenters circulation

Cholesterol forms plaque deposits on inside of blood vessels (atherosclerosis) Narrows blood vessel diameter Lowers blood flow Can lead to heart attack, stroke, kidney disfunction or other problems

Levels of LDL and HDL Most cholesterol is carried by LDL Normal plasma levels are 175 mg/100 mL LDL is removed from circulation if there are enough LDL receptors on cells Number of LDL receptors controlled by feedback mechanism High cholesterol inside cell suppresses receptor synthesis Hypercholesterolemia: not enough LDL receptors High plasma cholesterol levels (up to 680 mg/100 mL)

Levels of LDL and HDL High LDL together with low HDL is a symptom of faulty cholesterol transport and a warning of possible atherosclerosis Serum cholesterol level controls cholesterol synthesis in the liver High serum cholesterol results in low synthesis of cholesterol in liver, and vice versa Statin drugs inhibit the synthesis of cholesterol

Steroid Hormones Androgens: male sex hormones synthesized in the testes responsible for the development of male secondary sex characteristics

Steroid Hormones Among the synthetic anabolic steroids are

Steroid Hormones Estrogens: female sex hormones synthesized in the ovaries responsible for the development of female secondary sex characteristics and control of the menstrual cycle

Steroid Hormones Progesterone-like analogs are used in oral contraceptives

Steroid Hormones Glucorticoid hormones synthesized in the adrenal cortex regulate metabolism of carbohydrates involved in the reaction to stress decrease inflammation

Bile Salts Bile salts, the oxidation products of cholesterol synthesized in the liver, stored in the gallbladder, and secreted into the intestine where they emulsify dietary fats and aid in their absorption and digestion

Prostaglandins Prostaglandins: a family of compounds that have the 20-carbon skeleton of prostanoic acid

Prostaglandins Prostaglandins are synthesized in response to specific physiological triggers Made from membrane-bound 20-carbon polyunsaturated fatty acids such as arachidonic acid

Prostaglandins

COX Enzymes COX enzyme occurs in two forms COX-1 catalyzes the normal physiological production of prostaglandins COX-2 is responsible for the production of prostaglandins in inflammation when a tissue is injured or damaged, special inflammatory cells invade the injured tissue and interact with tissue cells interaction activates COX-2 and prostaglandins are synthesized

Thromboxanes Thromboxanes are also derived from arachidonic acid thromboxane A2 induces platelet aggregation and vasoconstriction aspirin and other NSAIDs inhibit the synthesis of thromboxanes by inhibiting the COX enzyme

Leukotrienes Synthesized from arachidonic acid occur mainly in leukocytes produce muscle contractions, especially in the lungs and thereby can cause asthma-like attacks 100 times more potent than histamine Many new anti-asthma drugs inhibit the synthesis of leukotrienes