Chapter 8

Lipids and Proteins are Associated in Biological Membranes

Lipids: heterogenous class of naturally occurring organic compounds classified together on the basis of common solubility properties

• insoluble in water but soluble in aprotic organic solvents

• amphipathic: one polar and one hydrophobic end

• open chain forms: fatty acids, triacylglycerols, sphingolipids, phosphoacylglycerols, glycolipids, lipid-soluble vitamins, prostaglandins, leukotrienes, thromboxanes

• cyclic forms: cholesterol, steroid hormons, bile acids

Biological functions of lipids

• storage of energy (reduced compounds, hydrophobic nature)

• insulation from environment (low thermal conductivity, high heat capacity, mechanical protection)

• water repellant (hydrophobic nature)

• buoyancy control and acoustics in marine mammals

Fatty acids: carboxylic acids with hydrocarbon chains containing 4-36 carbons

• most are unbranched with even number of carbons

• saturated: no double bonds between carbons

• monounsaturated: one double bond between carbons in alkyl chain

• polyunsaturated: more than one double bond in alkyl chain

• derived from hydrolysis of animal fats, vegetable oils, or phosphodiacylglycerols of biological membranes

• basic unit to most lipids

• nomenclature

  • number of carbon atoms:number of double bonds (double bond position)

  • length plays a role in chemical character

    • more carbons = higher melting point

  • cis isomer predominates

    • introduces kink in the chain causing disorder in packing

      • greater fluidity in membranes with cis-double bonds vs. saturated fatty acid chains

  • greater degree of unsaturation = lower melting points

Glycerolipids (triacylglycerols and triglycerides): glycerol ester with three fatty acids

• solid = fats

• liquid = oils

• primary storage form of lipids (body fat)

• less soluble in water due to lack of charged carboxylate group

• less dense than water (fats and oils float)

Fats provide efficient fuel storage

• fatty acids carry more energy per carbon (more reduced)

• fatty acids carry less water (nonpolar)

• carbohydrates are for short-term energy needs, quick delivery

• fats are for long-term energy needs, good storage, slow delivery

Phosphoacylglycerols (glycerophospholipids)

• one alcohol group of glycerol is esterified by a phosphoric acid rather than a carboxylic acid, producing phosphatidic acid

  • found in plant and animal membranes

• common glycerophospholipids:

  • PC: phosphatidylcholine

  • PE: phosphatidylethanolamine

  • PS: phosphatidylserine

  • PG: phosphatidylglycerol

  • PI: phosphatidylinositol

Waxes: complex mixture of esters of long-chain carboxylic acids and alcohols

• found as protective coatings for plants and animals

Ceramide based lipids

• backbone is not glycerol

• backbone is shingosine, an 18 carbon amino alcohol

• ceramide: attachment of fatty acid to sphingosine via amide linkage

Shingolipids: sphingosine backbone

• found in plants and animals, abundant in nervous system (myelin)

• structural similarity to phospholipids

Glycolipids: carbohydrate bound to -OH of the lipid

• sugar is either glucose or galactose

  • many glycolipids are derived from ceramides

• gangliosides: glycolipids with complex carbohydrate moiety that contains more than three sugars

Eicosanoid (cell signaling lipid): any naturally occurring substances derived from 20-carbon polyunsaturated fatty acids

• include prostaglandins, thromboxanes, and leukotrienes which function as hormones

Terpenes: derived from 5'-carbon isoprene unit

• steroids: group of lipids that have fused ring structure of 3 six-membered rings and 1 five-membered ring

• cholesterol: steroid from 27-carbon lipid where carbons are derived from acetate

  • made from acetyl-CoA in four stages

  • competitive inhibitors of HMG-CoA reductase lower serum cholesterol levels (statins) (lipitor)

  • Use of cholesterol:

    • key component of cell membranes

    • biosynthetic precursor to bile acid, bile salts, and steroid hormones

Biological membranes (plasma membrane)

• eukaryotic cells also have membrane-enclosed organelles

• molecular basis of membrane structure is in lipid components

  • polar head groups in contact with aqueous environment

  • nonpolar tails buried within the bilayer

  • hydrophobic interaction is the major driving force forming lipid bilayer

  • arrangement of hydrocarbon tails in interior can be rigid or fluid

• biological lipids: often amphipathic

  • when added to water, specific structures form to minimize contact between hydrophobic tails and water

    • low lipid = monolayer forms at air-water interface

    • high lipid = micelles form

      • hydrophobic tail in center, polar head face aqueous solution

      • cmc: critical micelle concentration

• membrane layers

  • inner and outer layers contain mixture of lipids

  • compositions on inside and outside can be different (distinguishable)

  • lipid bilayer: nonpolar tails face each other, polar heads face aqueous solution

    • polar surface contains charged groups

    • cells have ability to change shape without loss of integrity

      • fluid: acyl chains are in a liquid-ordered state

        • limited organization of acyl chains and limited lateral motion

        • fluidity is regulated

          • more unsaturated fatty acids = more fluidity

          • more shorter-chain fatty acids = more fluidity

          • cholesterol content of membrane

            • high temp = cholesterol decreases fluidity

            • low temp = cholesterol increases fluidity

          • temperature

            • heat causes membrane to become more disordered (higher for more rigid)

            • mobility of lipid chains increases

Fluid mosaic model of membranes

• fluid: lateral motion of components (proteins float and can move along plane)

• mosaic: components exist side-by-side as separate entities

  • structure of lipid bilayer with proteins, glycolipids, and steroids

  • no complexes are formed

• lipids form viscous, 2D solvent which proteins are inserted and integrated

  • lipids and proteins are capable of lateral and rotational movement

    • integral proteins: firmly associated with membrane, often spanning the bilayer

      • removed by treatment with detergents or ultrasonification

    • peripheral proteins: weakly associated with membrane, can be removed easily

      • removed by raising ionic strength

Protein-membrane interactions

• some proteins only interact with the membrane after the covalent attachment of a hydrophobic group to the protein

  • cysteine or serine palmitoylation

  • N-terminal myristoylation

  • C-terminal farnesylation or geranylation

  • C-terminal attachment of complex glycolipid

Transport across membranes

• some solutes pass across membranes

  • passive or simple diffusion: protein independent and driven by a concentration gradient

    • no input of energy

  • protein (transporter) dependent: requires transport protein (permeases)

    • passive transport or facilitated diffusion: protein dependent and driven by concentration gradient

      • no input of energy

      • transport protein accelerates movement of solute

      • protein pores, carrier molecules, permeases

    • active transport: protein dependent but not driven by concentration gradient

      • requires input of energy

        • primary active transport: energy released by ATP hydrolysis drives solute movement against gradient

        • secondary active transport: gradient of one ion has been established by primary active transport, providing energy to drive cotransport of second solute against gradient