Lipids and MembranesLipids and Membranes

Moshtaghi-KashanianMoshtaghi-Kashanian

Pathological BiochemistPathological Biochemist

Kerman University of Medical SciencesKerman University of Medical Sciences

LipidsLipids

• Lipids: a heterogeneous class of naturally occurring Lipids: a heterogeneous class of naturally occurring organic compounds classified together on the basis of organic compounds classified together on the basis of common solubility propertiescommon solubility properties

• They are insoluble in water, but soluble in aprotic They are insoluble in water, but soluble in aprotic

organic solvents, including diethyl ether, chloroform, organic solvents, including diethyl ether, chloroform, methylene chloride, and acetonemethylene chloride, and acetone

• Lipids includeLipids include

• triacylglycerols, phosphodiacylglycerols, sphingolipids, triacylglycerols, phosphodiacylglycerols, sphingolipids, glycolipids, lipid-soluble vitamins, and prostaglandinsglycolipids, lipid-soluble vitamins, and prostaglandins

• cholesterol, steroid hormones, and bile acidscholesterol, steroid hormones, and bile acids

Fatty AcidsFatty Acids

• Fatty acid: a long, un-branched chain carboxylic acid, Fatty acid: a long, un-branched chain carboxylic acid, most commonly of 12 - 20 carbons, derived from most commonly of 12 - 20 carbons, derived from hydrolysis of animal fats, vegetable oils, or hydrolysis of animal fats, vegetable oils, or phosphodiacylglycerols of biological membranesphosphodiacylglycerols of biological membranes

• In the shorthand notation for fatty acidsIn the shorthand notation for fatty acids

• the number of carbons and the number of double bonds in the the number of carbons and the number of double bonds in the chain are shown by two numbers, separated by a colonchain are shown by two numbers, separated by a colon

Fatty AcidsFatty Acids

Fatty AcidsFatty Acids

Among the fatty acids most abundant in plants Among the fatty acids most abundant in plants and animalsand animals

• Nearly all have an even number of carbon atoms, most Nearly all have an even number of carbon atoms, most between 12 and 20, in an un-branched chainbetween 12 and 20, in an un-branched chain

• The three most abundant are palmitic (16:0), stearic acid The three most abundant are palmitic (16:0), stearic acid (18:0), and oleic acid (18:1)(18:0), and oleic acid (18:1)

• In most unsaturated fatty acids, the cis isomer predominates; In most unsaturated fatty acids, the cis isomer predominates; the trans isomer is rarethe trans isomer is rare

• unsaturated fatty acids have lower melting points than their unsaturated fatty acids have lower melting points than their saturated counterparts; the greater the degree of unsaturation, saturated counterparts; the greater the degree of unsaturation, the lower the melting pointthe lower the melting point

TriacylglycerolsTriacylglycerols• Triacylglycerol (triglyceride): an ester of Triacylglycerol (triglyceride): an ester of

glycerol with three fatty acidsglycerol with three fatty acids

• natural soaps are prepared by boiling natural soaps are prepared by boiling triglycerides (animal fats or vegetable oils) triglycerides (animal fats or vegetable oils) with NaOH, in a reaction called with NaOH, in a reaction called saponification (Latin, saponification (Latin, saposapo, soap, soap

SoapsSoaps

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

PhosphoacylglycerolsPhosphoacylglycerols

• Phosphoacylglycerols (phosphoglycerides) are the second most Phosphoacylglycerols (phosphoglycerides) are the second most abundant group of naturally occurring lipidsabundant group of naturally occurring lipids

• found almost exclusively in plant and animal membranes, found almost exclusively in plant and animal membranes, which typically consist of 40% -50% phosphoacylglycerols and which typically consist of 40% -50% phosphoacylglycerols and 50% - 60% proteins50% - 60% proteins

• the most abundant phosphoacylglycerols are derived from the most abundant phosphoacylglycerols are derived from phosphatidic acid, a molecule in which glycerol is esterified phosphatidic acid, a molecule in which glycerol is esterified with two molecules of fatty acid and one of phosphoric acidwith two molecules of fatty acid and one of phosphoric acid

• the three most abundant fatty acids in phosphatidic acids are the three most abundant fatty acids in phosphatidic acids are palmitic acid (16:0), stearic acid (18:0), and oleic acid (18:1)palmitic acid (16:0), stearic acid (18:0), and oleic acid (18:1)

PhosphoacylglycerolsPhosphoacylglycerols

• A phosphatidic acidA phosphatidic acid

• further esterification with a low-molecular weight further esterification with a low-molecular weight alcohol gives a phosphoacylglycerolalcohol gives a phosphoacylglycerol

• among the most common of these low-molecularamong the most common of these low-molecular

PhosphoacylglycerolsPhosphoacylglycerols

Phosphoacylglycerols Phosphoacylglycerols

• A lecithinA lecithin

Phosphoacylglycerols Phosphoacylglycerols

WaxeWaxe• Esters of long-chain fatty acids and alcoholsEsters of long-chain fatty acids and alcohols

• from the Old English word from the Old English word weax weax = honeycom= honeycom

SphingolipidsSphingolipids

GlycolipidsGlycolipids• Glycolipid: a compound in which a Glycolipid: a compound in which a

carbohydrate is bound to an -OH of the carbohydrate is bound to an -OH of the lipidlipidmany glycolipids are derived from many glycolipids are derived from ceramidesceramides

SteroidsSteroids

• Steroids: a group of plant and animal lipids Steroids: a group of plant and animal lipids that have this tetracyclic ring structurethat have this tetracyclic ring structure

• The features common to the ring system of The features common to the ring system of most naturally occurring steroids are most naturally occurring steroids are illustrated on the next screenillustrated on the next screen

Steroids Steroids

Cholesterol Cholesterol

AndrogensAndrogens

• Androgens - male sex hormonesAndrogens - male sex hormones

• synthesized in the testessynthesized in the testes

• responsible for the development of male responsible for the development of male secondary sex characteristicssecondary sex characteristics

AndrogensAndrogens

EstrogensEstrogens

• Estrogens - female sex hormonesEstrogens - female sex hormones

• synthesized in the ovariessynthesized in the ovaries

• responsible for the development of female responsible for the development of female secondary sex characteristics and control of secondary sex characteristics and control of the menstrual cyclethe menstrual cycle

EstrogensEstrogens

Biological MembranesBiological Membranes• In aqueous solution, phosphoglycerides In aqueous solution, phosphoglycerides

spontaneously form into a lipid bilayer, with a back-spontaneously form into a lipid bilayer, with a back-to-back arrangement of lipid monolayersto-back arrangement of lipid monolayers

• polar head are in contact with the aqueous polar head are in contact with the aqueous environmentenvironment

• nonpolar tails are buried within the bilayernonpolar tails are buried within the bilayer

• the major force driving the formation of lipid the major force driving the formation of lipid bilayers is hydrophobic interactionbilayers is hydrophobic interaction

• the arrangement of hydrocarbon tails in the interior the arrangement of hydrocarbon tails in the interior can be rigid (if rich in saturated fatty acids) or fluid can be rigid (if rich in saturated fatty acids) or fluid (if rich in unsaturated fatty acids)(if rich in unsaturated fatty acids)

Biological MembranesBiological Membranes

• the presence of cholesterol increases rigiditythe presence of cholesterol increases rigidity

• with heat, membranes become more disordered; the with heat, membranes become more disordered; the transition temperature is higher for more rigid transition temperature is higher for more rigid membranes; it is lower for less rigid membranesmembranes; it is lower for less rigid membranes

Membrane ProteinsMembrane Proteins• Functions: transport substances across membranes, receptor Functions: transport substances across membranes, receptor

sites, and sites of enzyme catalysissites, and sites of enzyme catalysis

• Peripheral proteinsPeripheral proteins

• bound by electrostatic interactionsbound by electrostatic interactions

• can be removed by raising the ionic strengthcan be removed by raising the ionic strength

• Integral proteinsIntegral proteins

• bound tightly to the interior of the membranebound tightly to the interior of the membrane

• removed by treatment with detergents or ultrasonificationremoved by treatment with detergents or ultrasonification

• removal generally denatures themremoval generally denatures them

Fluid Mosaic ModelFluid Mosaic Model

• Fluid: there is lateral motion of components in the membrane; Fluid: there is lateral motion of components in the membrane;

• proteins, for example, “float” in the membrane and can proteins, for example, “float” in the membrane and can move along its planemove along its plane

• Mosaic:components in the membrane exist side-by-side as Mosaic:components in the membrane exist side-by-side as separate entitiesseparate entities

• the basic structure is that of a lipid bilayer with proteins, the basic structure is that of a lipid bilayer with proteins, glycolipids, and steroids such as cholesterol embedded in itglycolipids, and steroids such as cholesterol embedded in it

• no complexes, as for example, lipid-protein complexes, are no complexes, as for example, lipid-protein complexes, are formedformed

Membrane TransportMembrane Transport• Passive transportPassive transport

• driven by a concentration gradient driven by a concentration gradient

• simple diffusion: a molecule or ion moves through an opening simple diffusion: a molecule or ion moves through an opening created by a channel proteincreated by a channel protein

• facilitated diffusion: molecule or ion is carried across a facilitated diffusion: molecule or ion is carried across a membrane by a carrier proteinmembrane by a carrier protein

• Active transport Active transport

• a molecule or ion is moved against a concentration gradienta molecule or ion is moved against a concentration gradient

• see the Na+/K+ ion pumpsee the Na+/K+ ion pump

Membrane ReceptorsMembrane Receptors

• Membrane receptorsMembrane receptors

• generally oligomeric proteinsgenerally oligomeric proteins

• binding of a biologically active substance to a receptor binding of a biologically active substance to a receptor initiates an action within the cellinitiates an action within the cell

Lipid-Soluble VitaminsLipid-Soluble Vitamins

• Vitamins are divided into two broad Vitamins are divided into two broad classes on the basis of their solubilityclasses on the basis of their solubility

. . Those that are water-solubleThose that are water-soluble

. Those that are lipid-soluble (and hence . Those that are lipid-soluble (and hence classified as lipids) classified as lipids)

The lipid-soluble vitamins include A, D, E, and KThe lipid-soluble vitamins include A, D, E, and K

ProstaglandinsProstaglandins

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

ProstaglandinsProstaglandins

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

• one such polyunsaturated fatty acid is one such polyunsaturated fatty acid is arachidonic acidarachidonic acid

ProstaglandinsProstaglandins

• among those synthesized from among those synthesized from arachidonic acid arearachidonic acid are

ProstaglandinsProstaglandins• Research on the involvement of PGs in Research on the involvement of PGs in

reproductive physiology has produced reproductive physiology has produced several clinically useful derivativesseveral clinically useful derivatives

• 15-Methyl-PGF2a is used as a therapeutic 15-Methyl-PGF2a is used as a therapeutic abortifacientabortifacient

ProstaglandinsProstaglandins• the PGE1 analog, misoprostol, is used for the PGE1 analog, misoprostol, is used for

prevention of ulceration associated with the prevention of ulceration associated with the use of aspirin-like non-steroidal use of aspirin-like non-steroidal antiinflammatory drugs (NSAIDs)antiinflammatory drugs (NSAIDs)

LeukotrienesLeukotrienes• Leukotrienes: derived from arachidonic acidLeukotrienes: derived from arachidonic acid

• found in white blood cells (leukocytes)found in white blood cells (leukocytes)

• an important property is constriction of smooth muscles, an important property is constriction of smooth muscles, especially in the lungsespecially in the lungs

ThromboxanesThromboxanes• derived from arachidonic acidderived from arachidonic acid

• contain a four-membered cyclic ether within contain a four-membered cyclic ether within a six-membered ringa six-membered ringinduce platelet aggregation and smooth induce platelet aggregation and smooth muscle contractionmuscle contraction