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by: Adah McCullough III


Adah McCullough III
GPA 3.64


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Class Notes
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This 41 page Class Notes was uploaded by Adah McCullough III on Saturday September 12, 2015. The Class Notes belongs to BCMB 3100 at University of Georgia taught by Staff in Fall. Since its upload, it has received 40 views. For similar materials see /class/202194/bcmb-3100-university-of-georgia in Biochemistry and Molecular Biology at University of Georgia.

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Date Created: 09/12/15
Chapter 9 Lipids and Membranes Problems 1 36 9 10 11 14 16 Lipids are essential components of all living organisms 39 Lipids are water insoluble organic compounds 39 They are hydrophobic nonpolar or amphipathic containing both nonpolar and polar regions Fig 91 Structural relationships of major lipid classes Imus 1 Fatty Acids Meioids me rmpems mmmm i i 2 Isoprenoids Emumnmm Yrmcyigivrumi Mm Sphmguhpuix Glycei Cphasplnhpids mum l msumk gm pumpimimm Sphmgmiyclm Ccmlnwdcs mam Hunkx i39hnstuuyL mi Elimn iimiill s mwnundyi l hmivimluiyl Him ma mum mum pimspiwiipms glyuusplimgnhpids 3 Phospholipids 4 Glycoshingolipids 92 Fatty Acids Common lauric acid Fa Y add IUPAC dodecanoic acid Fa39H39y acyl Abbrev C12 0 group 7 H d b y r on Other fem acids examg les Myr39isfic re39rr39odecanoic 6140 Polmific hexadeconoic 6160 rearic octadecanoic 6180 13 910 v IV Unsaturated Fatty Acids Common palmitoleic acid IUPAC cisA9hexadecenoic acid Abbrev 61619 Other unsaturated fam acids examglesl Oeic cisA9octadecenoic 61819 Linoeic ciscisA93912octadecadienoic 618293912 Another nomenclature system 6182912 is also known as an co6 fatty acid ie the last double bond is 6 carbons from the end of the fatty acid chain Unsaturated Fatty Acids Melfing poinfs 70 C 13 C 17 C Triacylglycerol 39 Fatty acids are important metabolic fuels 23 times the energy of proteins or carbohydrates Fatty acids are stored as neutral lipids called triaclyglycerols T Gs TGs are composed of 3 fatty acyl residues esterified to a glycerol 3 carbon sugar alcohol TGs are very hydrophobic and are stored in cells in an anhydrous form eg in fat droplets TGs are catabolized by Iipases Digestion requires bile salts solubilize TGs Transport of TGs is accomplished through lipoproteins Phospholipids a 09 b l 0P709 Glycerol 3rpilosphule The most abundanf lipids in membranes Possess 1 glycerol backbone A phosphafe is esTerified To bo l glycerol and anofher compound bearing an OH group Phosphafidafes are glyceropllospholipids wifh Two fatty acid groups esferified To 3 1 and 6 2 of glycerol 3plIOSpl10TZ ll 04 RI 03 Polar head 0 P 7 9 hydmpllilic Nonpnlur tails hydmphobic R1 Pllospllalidate Fig 97 Types of glycerophospholipids o Phosphotidyl e l39honolomine b Phosphofidyl serine c Phosphofidyl choline Functional groups from esterified alcohols are shown in blue General names refer To a family of compounds a V V V m I klhmmlmnmu L W Ir U U 39 P U 6 H16 7 EH 4 11 0 L 07c 70 x Rn Phoxphmlaymmnommme Ph hnlb se A1 0 C Q NH H c N CH H U HY 39 39 H Senna lmlma H CH Polar heads mydmpmlic n sphnl pcse D 7 P U V splinle c Y 1 HIE EH CH1 mydmpnomm K S VV 2 1 RM E 7 l 1 Pnowmuaywscmw Phnsphzmdylchnhnc Fig 99 Structure of an ethanolamine plasmalogen l 700 Plasmalogens C1 6444 hydrocarbon substituent n 2 4 attached by a vinyl ether t i F0 linkage not ester quotC linkage g 95 Spshingolipids Sphingolipids sphingosine frons4sphingenine is The backbone abundant in central nervous system 39l39issues Ceramides furry acyl group linked to 62 of sphingosine by an amide bond Sphingomyeins phosphocholine o oched l39o C1 of ceramide a CH3 O OCHZCH2il CH3 OH CH3 a HO OH I 3 l H1C CH CH NH H HCE Trans CHI kc H 1 Sphingosme mmx 4 Sphingcninc bi ml le ch 39 23H C 14 rim 3 0 C 14 y c H 3 xi 5H CHE if CH2 fI H 1 CH 1 TCH lt1 Iquot CHI 1 R X C H1 7le H 1 CH 1 wk H 1 C erumide Gamma gl ycosphmgololplds wfrh one HM Hz HCH monosaccharIde resndue W 0 gm CH o o a H qtfached Via a glycosndnci W H 2 03 Hg linkage 1390 C1 of ceramlde quot quot CH ll HH 39 BD Galaclose C33 3 CH CH3 CH3 39Galactosylcerebrosudes cg galac rosylceramides a single BD pr galacfose as a polar head group R Csj H 39 2 CH2 CH2 CH2 CH3 Garlgliosides contain oligosaccharide chains with N acetyl neuraminic acid NeuNAc attached to a ceram39de More than 60 structures Structures provide unique surfaces that define blood types and tissue types 7 391 l39r39 Structures change during development e Metabolic defects are extremely debilitating and often atal EH CH3011 H1 d 7 CHich I TH ll 7 HC 0 0 CHzlu CHEM H CH CH 39 H OH I B D7Galaclnse HqC O NsAcelylr snsg laclosamine 96 Steroids Classified as isoprenoids related to 5carbon isoprene found in membranes of eukaryotes Steroids contain four fused ring systems 3six carbon rings ABC and a 5carbon D ring H3C CH2 Ring system is nearly planar H CC Substituents point either down a or up b 2 2 34 27 a 1 2 l 8 7 3 OH 2 ol I 3 26 CO 03918quot 71L 399 9 C 14sz l6 COOH 2 quotatequot 2 vlf Iquot 3 A B H O 39 slr 4 6 Cholesterol H0 Some other Steroids b 3939 D gt q A B r Stigmasterol 3 plant sterol vCOOI39 Na CD Sodium cholate a bile salt C OH C D A j 13 O Testosterone a steroid hormone e OLA Ergostcrol a stem from fungi and yeast Functions and Properties of Cholesterol Cholesterol modulates the fluidity of mammalian cell membranes 39 It is also a precursor of the steroid hormones and bile salts 39 It is a sterol has hydroxyl group at C3 39 The fused ring system makes cholesterol less flexible than most other lipids 39 Cholesterol is converted to cholesteryl esters for cell storage or transport in blood Fatty acid is esterified to C3 OH of cholesterol Cholesterol esters are very water insoluble and must be complexed with phospholipids or amphipathic proteins for transport 97 Other Biologically Important Lipids Waxes are nonpolar esters of longchain fatty acids and long chain monohydroxylic alcohols Waxes are very water insoluble and high melting They are widely distributed in nature as protective waterproof coatings on leaves fruits animal skin fur feathers and exoskeletons 0 H3C CH214 c O CH229 CH3 Eicosanoids a 00e Amhidomc acid mm b 0 UAVA e Pmslaglundin E m C00 FM 39 n E HO OH Eicosnnoids are oxygenafed derivafives of CEO polyunsafurafed faffy acids 29 arachidonic ac39 Pmsfaglandins eioosanoids having a cyclopenmne ring Aspirin alleviafes pain fever and inflammafion by inhibifing file synfhesis of prosfaglandins Other Eicosanoids c V Wavoe Thmubome A2 6 0 W10 d Lcukmricne D4 V CHicinicnzi C00e lt9erx Prosfaglandin E2 can cause consfr ic on of blood vessels Thromboxane A2 involved in blood clof fonnafion Leukofr iene D4 mediafor of smoo l muscle oonfr acfion and bronchial consfr ic on seen in as lmafics Fig 9 20 Some Isopr39enoids Lipid vitamins ADE and K are isopr39enoid derivatives a b C Li m onene 9 Bacloprcnol Undecaprenyl alcohol Juvenile hormone CHZOH 0 CH3 Biological Membranes Datum u m ulw I oi 1gmacchande mm or Oligusnrchamlc glympmiems mum of glycosphmgolipids Li 17 minim Pcnphel I mow memm mm pa pimi lemme i 4 y g lmegml imegni A 47 i membrane A 7 prom praiciils Biologicol membranes define the external boundaries of cells and separate cellular compartments Lipid bilayers are the structural basis for all biological membranes 39Polar head groups contact aqueous medium 39Nonpolar l ails point toward the interior Biological Membranes a b Polar head I hydrophilic Nonpolar Aquef us taquot solution hydrophobic Figure 920 Principles of Biochemistry 42 E 2006 Pearson Prentice Hall Inc Fluid Mosaic Model of the Membrane mum iuwm Olligouc f hmide legusarclmmle a mm o r chums of glycopimems 1 glycosphlngolipids Lipld mnwi Pmphcm mum membme prawn Penplieml mulbch H mm 710mm 39 Fluid mosaic model membrane proteins and lipids can rapidly diffuse laterally or rotate within the bilayer proteins quotfloatquot in a lipid bilayer sea 39 Membranes a25 50 lipid and 50 75 proteins Lipids include phospholipids glycosphingolipids cholesterol in some eukaryotes Compositions of biological membranes vary considerably among species and cell types 99 Lipid Bilayers and Membranes Are Dynamic Structures liiiliilliiii liiilllliliii Will 98 888888 8888888888888 Wt ggggg Pas Vex s ow Ordered gel phase Disordered liquid iiiiiiiiiiiii iiiiiiiiiiiii 8888888888 88888 Hum properties of my depend upon the flexibility of their fatty acid chains a Lateral diffusion is very rapid Unsaturated fatty acids more b Transverse diffusion flip fluid membrane transition flop is very slow occurs at a lower Temperature 99 Lipid Bilayer39s and Membranes Ar39e Dynamic Structures Human cell Mouse cell 0 Red fluorescent Green fluorescent markers markers l Fusion l Immediately after fusion fluorescent markers remain localized Within 40 minutes fluorescent markers appear to be randomly distributed over the entire surface Figure 9 23 Principles of Biochemistry Ale 2006 Pearson Prentice Hall lnc Fig 927 Effect of bilayer composition cholesterol on phase transition Pure phospholipid 100 bilayer red has a sharp phase transition Mixed lipid blue bilayer undergoes a 5039 broader phase 1 transition 1 Tm i I 0 I I I I l Percentage of lipid in liquid crystalline phase 10 2O 30 40 Temperature C 910 Three Classes of Membrane Proteins 1 Integral membrane proteins or intrinsic proteins or transmembrane proteins Contain hydrophobquot regions embedded in the Peripheral membrane proteins Associated with membrane through chargecharge or hydrogen bonding interactions to integral proteins or membrane lipids More readily dissociated from membranes than covalently bound proteins Change in pH or ionic strength often releases these proteins Lipidanchored membrane proteins Tethered to membrane through a covalent bond to a lipid anchor as 1 Protein amino acid side chain ester or amide link to fatty acyl group eg myristate palmitate 2 Protein cysteine sulfur atom c a Promquot covalently linked to an isoprenOId chain prenylated proteins 7C 7 N 3 Protein anchored to lesphu glycosylphosphatidylinositol GPI clhannluminc residue 7 l m i 39 quot quot i39 n n Mun ilL N l i gt 2 1 l i l I l l 1 u l l l l l l fCHj l l l l l H l L l s 3 1 i i i a i 3 v I wgi 0 met i l l i 3i i i x i l i i i l ILL in Clly lea et 5 l l i lt i If i l 13 11 l a i X 1quotquot ltFC J k i J i c i i 3 i i c a I if P i x lc0l H A s in ii A ulur l l l l l l l x i 7 l V l l 39r leaflet c i 3 l x t p Ill i s gt i quot quot395 jquot r l P l l l l i PIOICIH iolem a b 911 Membrane Transport Three Types of integral membrane protein Transport 1 Channels and pores 2 Passive 39rranspor39rers 3 Active 39rranspor39rers Chemical AG39l39ranspor39l39 AoufD Aswanst 23038325298log1100 114 kJmol Electrical T T I A P ALPquot A Pom amp AG 3 AG39l39ranspor39l39 ZFALP Fig 930 Pore or channel Pores and channels are transmembrane proteins with a 0 central passage for ions and small 0 a 0 O molecules 0 0 Salutes of appropriate size charge and molecular structure can diffuse down a concentration gradient high to low Process requires no energy Rate may approach diffusion controlled limit Passive Transport Passive transport facilitated diffusion does not require an energy source Protein binds solutes and transports them down a concentration gradient Uniport transporter carries only a single type of solute Some transporters carry out cotransport 01 m two solutes either in the m direction symport or in 02 p osite directions antiport Uniport Symport Antiport Fig 932 Kinetics of passive transport Initial rate of max transport increases until a maximum is v0 Vim o 0 a a a 3 o I a o a a 2 I reached sute Simple Diffusion is saturated a 0 39 0 Ktr SOm Ktr out Extracellular space primary and secondary Oxidation of SW generates a transmembrane proton gradient Movement of H down its gradient drives C tosol lactose transport y lactose permease LXTRACELLULAR SPACE K6 5 mM 3N Requures energy 39N quot 45 M Up a concentration gradient CYTOSOL 2 K P Nu Glucose I K J 140 mM N419 1 5 15 mM TABLE 93 Characteristics of different types of membrane transport Movement Saturable relative to Energy Protein with concentration input carrier substrate gradient required Simple diffusion No No Down No Channels and pores Yes No Down No Passive transport Yes Yes Down No Active transport Primary Yes Yes Up Yes direct source Secondary Yes Yes Up Yes ion gradient Tabie 93 Principles of Biothemistry Ale 2006 Pearson Prentice Hall ln Endocytosis and Exocytosis Cells importexport molecules too large to be transported via pores channels or proteins by Endocytosis macromolecules are engulfed by plasma membrane and brought into the cell inside a lipid vesicle Exocytosis materials to be excreted from the cell are enclosed in vesicles by the Golgi vesicles then fuse with plasma membrane Signal Transduction Exlcmal stimulus Firsl messenger 5pecific receptors in I b Membrane lgt Transducer Igt Effector PLASMA P asma mem r anes rcccpmr enzyme MEMBRANE respond to external chemicals ligands S d CCOl messengsx39 that cannot cross the Cytoplasmic and nuclear effectors neurotransmitters Cellularl espnnse Signal is passed through membrane protein transducer to a membranebound effector enzyme Effector enzyme generates a second messenger which diffuses to intracellular target Amplification occurs when a single ligand receptor activates numerous tranducers resulting in multiple second messengers that activate multiple effectors 6 Proteins are Signal Transducers Many hormone receptors rely on Hormonerreccpmr guanine nucleotide binding proteins C0quot Plex G proteins as transducers GDP GTP G proteins have GTPase activity they slowly hydrolyze the bound GTP to GDP and Pi Two interconvertible forms of G b proteins an inactive GDP bound 0 form and an active GTPbound form Active Inactive G proteins consist of cup and 1 subunits The Ga GTP complex interacts with the effector enzyme Hydrolysis of GTP by the Gu GTP complex deactivates the G protein and Inmvc permits assembly of the inactive 6qu complex Imummry summery hunnone g Adenyl Cyclase Signaling Pathway Hormones active The G protein Gs Gs ac39l39iva39l39es adenxlxl A cyclase enzyme To produce ch 5am inaclivc P Phasphodicslcmsc cAMP ac39l39iva39l39es protein 233 kinases 39l39o phosphogla l e PWHJH Wn mmm cellular enzymes and affec39l39 metabolic pathway processes NH NNz ltN I N NHz ltJ NNAHOH no quotIj Ho r o r o li N Adelnyi z HO l O N N OH OH OH cyc use 3 CAMP I OH OH PPi oli o OH phosphodlesferase OH OH Ho The Iquot 5i39r039PhOSpholipid m j 7 Signaling Pathway quot lt a W h Prulc7OH Pocm4 A maJor sugnalTransduc hon Vquotquot pathway for some hormones PW CM growfh factors 2 second sail Ipw l m m 7 messengers mm 1 3 response Diacylglycerol and IP3 inosi39l39ol 145 39l39riphospha re are produced 24 from The membrane phospholipid 39 PIPE phospha ridylinosi rol 45 I H 30 blisphospha39l39e lt2 H Pi OH 1P3 activates a calcium channel H H JiLLEP Tz Diacylglycerol ac39riva39res grotein H H l kinase C PMSPTI39WC xo r ox Receptor Tyrosine Kinases TK TK is a multifunctional transmembrane protein containing a receptor a transducer and an effector Ligands EXTRACELLULAR SPACE 1m nvg tn ana LJr 539539 l YTOSOL Tyrosinekinase domains W ATP ADP Activation of Phosphorylated dimer Each domain receptor tyrosine phosphorylates cafalyzes kinases by cellular target phosphorylation of ligandinduced proteins its partner dimerization


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