Class Note for BIOC 462A at UA 2
Class Note for BIOC 462A at UA 2
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Date Created: 02/06/15
Biochemistry 462a Carbohydrate Function Reading Chapter 9 Practice problems Chapter 9 2 4a 4b 6 9 10 13 14 15 16a 17 Carbohydrate extra problems Signi cance and Functions of Carbohydrates Bacterial Cell Walls BHzlJH EHg H D h h J D Hui D NHCDCH MHCDCHa a HaC CL Ta T The cell walls of Grampositive bacteria consist Hac TH H of a polysaccharidepeptide complex called the D D peptidoglycan Long polysaccharide chains H H DH composed of alternating N acetylglucosamine T and Nacetylmuramic acid form the backbone W D El of the cell wall Attached to the lactate side TH 39 u chain of the muramic acid is a tetrapeptide L TD Ala D Glu L Lys D Ala Note the HM presence of Damino acids The polysaccharide grosslinkto 1H chains are joined together Via pentaglycines 3232 l My Teichoic acids made up of repeating units of EEG glycerol 0r ribitol phosphate are also a part of H the cell wall Hal 90 DNa Crossiink in LLys an next chain aws new MU 39 t a i v 55 w F mmhlvl tnii Cell walls of Gramrnegatlve bacteria are much more complex SandWiched between an inner and outer membrane is a layer of peplldoglycan The outer membrane is coated With lipopolysaccharide consisting of a lipid group Joined to a highly complex polysaccharide Repealing carbohydrate structures make thousands of dl aml antigenic groups With the antigenic determinant known as the Oranllgaquot Glycolipids and lysosomal storage diseases 1 Multiple carbohydrate structures bound to sphlngoslne 2 widely distributed on outer surface of cells 3 TayrSachs disease results from loss of hexosaminidase A s The structure ofthe glycollpld that builds up in the brain in TayrSachs disease and Cemld mcsmcmm leads to an irreversible neurological degenerauon that is always fatal SA GM Gangllusme Glycosaminoglycans and Proteoglycans in Extracellular Matrices and Connective Tissues Complex polysaccharide complexes ofvarylng sizes up to several million daltons r proteins Part ofmernbrane complexes or the extracellular matrix Some classes on cells bind growth factors and may be a kind of antennae to collect and store these factors 1n connective tissues the very hygroscopic complexes bind water and serve to cushion Joints Cartilage is exible and resiliant because ofthe glycosamlnoglycan part ofproleoglycans Glycosaminoglycans Elugummm MAmylwala xnmnpa sul n MrsAlfuwluuusamineiuulhl ChondrolIInAsullale Hepuln Glumnumte Glugumm Examples of some of the I I repea39mg d sacchmdes f NAaelylwalnrlaanm39nvSsulhl M mylulueuamine glycosamlnoglycans Nouns that long polymers W uld be EX EHdEdvW th Chondlollln sullale Hyalumnale muluple negauve eharges Idummh CullAtlas MArelylulueaennansasuuale MAz lyvluuanm39ngtSsu a Dermalln sullale Kelalln sullale Heparin an example of structure eomammg and repeaarrg dlsacchande umts Heparm forms extended structures due to H 0503 H NHSOS39 the charge repulslon of lts sulfate groups HEPARIN lelmglycnn nnm Car v IA cartoon ofaproteoglycan complex of eonneenye nssue ylllnnml Hurler39s synolrome ls one example of a lysosomal storage dlsease eauseol by loss of a degradatlve enzyme 1n th5 ease the enzyme terrlduromdase whlch nyolrolyzes glycosldl bonds lnyolylng Lrldurom aelol ls de clent Glycnprnteins Orllnked sugars ln glycoprotems CHZOH Pmleln Chzln 0H 0 H H R C 0 Nracetylgalactosamlne attaches to the protein OH H R H m CH3 yla a Star or anln Orlhked glycnprnteins H o Hcu H MHcocHz NH prmern cnam Mencwlndmnszmme Type 0 Among the O lt linked glycans are the blood group substances lt am lt smlb j GAL NAG o 0 MAG o Jat ltDgtPmn S I la Pmn 2 r T B r 39r A FU We FL We 0 Functions 0 Mucins contain large numbers of Olinked saccharides and protect mucous membranes in the respiratory and GI tracts o Carbohydrate gives an extended conformation to the protein leading to high viscosity and extensive networks 0 Some membrane receptors contain domains that are very rich in Olinked saccharides The extended conformations of such regions have been postulated to hold the ligand binding domain of some receptors out away from the carbohydrate complexes glycocalyx layer right at the cell surface The LDL reeeptor eohtarhs a earbohvotrate heh domam that may orreht the reeeptor above the eeu glycocalyx rhereasrhg the bdeng the LDL pamcle apoprotein LDL receptor ehanee of erinked sugarsin glycnprnteins 1h glveoproterhs earbohvotrate chams are attaehedto the proterh mmquot cm 1h ermked glveoproterhs Ne aeetvlglueosamrhe attaehes to the I proterhvrameamrdeNofahAsh 2 H2 W ermked glveoproterhs can have H 0 er Asn complex ohgosacchande chams 1 rot f The earbohvotrate moretv m OH H r glveoproterhs has hrgh mobrhtv Ser mob ht H NHCOCH 1h antibod es earbohvotrates chams serve a structural role holdmg the two heavy chams together Qgg NAcetylglucosamme Protem chain Examples nl39 Nelinked saccharide Structures ngll Mnnnuse lulum cumpm Type cur cur cur Man Mnn Iunu Mnn mu Man Gal Gnl Man Man Mnquot Mnquot Mnu Man hxu mu mu Chum0mm numbc l I l I t t I l l I l Man Man Man Mnn mu nun Mm Man Mnu Iunu I I t l I I Mm Man I Mr M n l l l l l cum amu uh u r Cle c mow l l l clown cum mm cuwu cumu Glueose and mannose eontarnrng ohgosaeehandes are added dunng translatron ln the endoplasmlc reueulum ER Tnmmlng remoyes termrnal glueose andmannose resldues Glyeoproterns that fold rneorreetly may have glueose added back a slgnal keeps the protern m the ER so that ehaperones ean eomplete proper foldlng Kthe protern has ahlgh mannose ollgosacchande addltlon of phosphate to mannose ls a slgnal to target the protern to lysosomes Modlflcauon of ohgosaeehandes oeeurs ln the clsmedla1 andtrans Golgl reglons Protozoans rneludmg yeast lack the ablllty to add GlcNAc to the mannose eore for synthesrs of complex ohgosaeehandes The enzyme GlcNAc TI Glucosamlnyl txansferase I that adds the flrst GlcNAc appears to separate metazoans from unlcellular protozoans Thls obseryatron ls rnterpreted to mean that the eellular rnteraeuons for mulueellular organlsms requlre complex ollgosaccharldes Ref Dennls et al Bloessays 21412 99 Knockrout mree are belng used to study the funeuons of the sugars Loss of the GlcNAc TIls lethal earlyln deyelopment Ohgosaeehandes on glyeoproterns are very heterogeneous wth muluple ollgosaccharlde struetures found at a slngle glyeosylatron srte on dlfferentmolecules Loss oftel39mlnal slall acld of complex ohgosaeehandes of old erreulaung glyeoproterns by aeuon of enzymes ln blood vessel walls eauses brndmgreeognrtron by hyer asraloglyeoprotern reeeptor leadlng to removal endoeytosrs and degadahon by lysosomes Lectins and cell adhesion proteins Proteins that speci cally bind to carbohydrates Originally discovered in plants but are important parts of the biology of all multicellular organisms Animal lectins include the selectins carbohydrate binding proteins on leukocytes and endothelial cells of vascular tissue Expressed in response to signals from pathogens these cause leukocytes and neutrophils to adhere to the vascular wall and move into infected tissues Waund introduces bacteria In ammation Iquot ii i 7 139 39 quotHBactena 439 39139 V t x r c Walls of blood stream Glanu amna
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