Lipids and Membranes Moshtaghi-Kashanian Pathological Biochemist Kerman University of Medical Sciences

Lipids Lipids: a heterogeneous class of naturally occurring organic compounds classified together on the basis of common solubility properties They are insoluble in water, but soluble in aprotic organic solvents, including diethyl ether, chloroform, methylene chloride, and acetone Lipids include triacylglycerols, phosphodiacylglycerols, sphingolipids, glycolipids, lipid-soluble vitamins, and prostaglandins cholesterol, steroid hormones, and bile acids

Fatty Acids Fatty acid: a long, un-branched chain carboxylic acid, most commonly of 12 - 20 carbons, derived from hydrolysis of animal fats, vegetable oils, or phosphodiacylglycerols of biological membranes In the shorthand notation for fatty acids the number of carbons and the number of double bonds in the chain are shown by two numbers, separated by a colon

Fatty Acids

Fatty Acids Among the fatty acids most abundant in plants and animals Nearly all have an even number of carbon atoms, most between 12 and 20, in an un-branched chain The three most abundant are palmitic (16:0), stearic acid (18:0), and oleic acid (18:1) In most unsaturated fatty acids, the cis isomer predominates; the trans isomer is rare unsaturated fatty acids have lower melting points than their saturated counterparts; the greater the degree of unsaturation, the lower the melting point

Triacylglycerols Triacylglycerol (triglyceride): an ester of glycerol with three fatty acids natural soaps are prepared by boiling triglycerides (animal fats or vegetable oils) with NaOH, in a reaction called saponification (Latin, sapo, soap

Soaps Soaps form water-insoluble salts when used in water containing Ca(II), Mg(II), and Fe(III) ions (hard water)

Phosphoacylglycerols Phosphoacylglycerols (phosphoglycerides) are the second most abundant group of naturally occurring lipids found almost exclusively in plant and animal membranes, which typically consist of 40% -50% phosphoacylglycerols and 50% - 60% proteins the most abundant phosphoacylglycerols are derived from phosphatidic acid, a molecule in which glycerol is esterified with two molecules of fatty acid and one of phosphoric acid the three most abundant fatty acids in phosphatidic acids are palmitic acid (16:0), stearic acid (18:0), and oleic acid (18:1)

Phosphoacylglycerols A phosphatidic acid further esterification with a low-molecular weight alcohol gives a phosphoacylglycerol among the most common of these low-molecular

Phosphoacylglycerols

Phosphoacylglycerols

Phosphoacylglycerols A lecithin

Waxe Esters of long-chain fatty acids and alcohols from the Old English word weax = honeycom

Sphingolipids

Glycolipids Glycolipid: a compound in which a carbohydrate is bound to an -OH of the lipid many glycolipids are derived from ceramides

Steroids Steroids: a group of plant and animal lipids that have this tetracyclic ring structure The features common to the ring system of most naturally occurring steroids are illustrated on the next screen

Steroids

Cholesterol

Androgens Androgens - male sex hormones synthesized in the testes responsible for the development of male secondary sex characteristics

Androgens

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

Estrogens

Biological Membranes In aqueous solution, phosphoglycerides spontaneously form into a lipid bilayer, with a back-to-back arrangement of lipid monolayers polar head are in contact with the aqueous environment nonpolar tails are buried within the bilayer the major force driving the formation of lipid bilayers is hydrophobic interaction the arrangement of hydrocarbon tails in the interior can be rigid (if rich in saturated fatty acids) or fluid (if rich in unsaturated fatty acids)

Biological Membranes the presence of cholesterol increases rigidity with heat, membranes become more disordered; the transition temperature is higher for more rigid membranes; it is lower for less rigid membranes

Membrane Proteins Functions: transport substances across membranes, receptor sites, and sites of enzyme catalysis Peripheral proteins bound by electrostatic interactions can be removed by raising the ionic strength Integral proteins bound tightly to the interior of the membrane removed by treatment with detergents or ultrasonification removal generally denatures them

Fluid Mosaic Model Fluid: there is lateral motion of components in the membrane; proteins, for example, “float” in the membrane and can move along its plane Mosaic:components in the membrane exist side-by-side as separate entities the basic structure is that of a lipid bilayer with proteins, glycolipids, and steroids such as cholesterol embedded in it no complexes, as for example, lipid-protein complexes, are formed

Membrane Transport Passive transport driven by a concentration gradient simple diffusion: a molecule or ion moves through an opening created by a channel protein facilitated diffusion: molecule or ion is carried across a membrane by a carrier protein Active transport a molecule or ion is moved against a concentration gradient see the Na+/K+ ion pump

Membrane Receptors Membrane receptors generally oligomeric proteins binding of a biologically active substance to a receptor initiates an action within the cell

Lipid-Soluble Vitamins Vitamins are divided into two broad classes on the basis of their solubility . Those that are water-soluble . Those that are lipid-soluble (and hence classified as lipids) The lipid-soluble vitamins include A, D, E, and K

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

Prostaglandins Prostaglandins are not stored in tissues as such, but are synthesized from membrane-bound 20-carbon polyunsaturated fatty acids in response to specific physiological triggers one such polyunsaturated fatty acid is arachidonic acid

Prostaglandins among those synthesized from arachidonic acid are

Prostaglandins Research on the involvement of PGs in reproductive physiology has produced several clinically useful derivatives 15-Methyl-PGF2a is used as a therapeutic abortifacient

Prostaglandins the PGE1 analog, misoprostol, is used for prevention of ulceration associated with the use of aspirin-like non-steroidal antiinflammatory drugs (NSAIDs)

Leukotrienes Leukotrienes: derived from arachidonic acid found in white blood cells (leukocytes) an important property is constriction of smooth muscles, especially in the lungs

Thromboxanes derived from arachidonic acid contain a four-membered cyclic ether within a six-membered ring induce platelet aggregation and smooth muscle contraction