Carbohydrates and Glycobiology

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1 1 Carbhydrates and Glycbilgy Carbhydrates are aldehyde r ketne derivatives f plyhydrxy alchls cntaining at least three carbn atms with the general frmula (CH 2 O) n They are mderately reduced cmpunds (sme xygen assciated with them) which can be cnverted int energy (ATP) quickly Uses 1) Energy strage, fuel, intermediates f metablism 2) Structural - DNA and RNA, cell walls in plants (cellulse), arthrpds skeletn (chitin) 3) Recgnitin - attached t lipids and prteins (bld types n red bld cells = antigens) Mnsaccharides - suffix "se" is used t designate sugars Building blcks --> plysaccharides (macrmlecules) D-Cnfiguratin is the mst cmmn in sugars synthesized by living rganisms D assignment is based n the cnfiguratin f the chiral carbn furthest frm the "anmeric" carbn C-1 in aldses & C-2 in ketses Tw majr mnsaccharide classes Aldses Ketses Aldses Structures based n D-glyceraldehyde which is the simplest aldse D is determined by the asymmetric carbn FURTHEST AWAY frm the aldehyde and is drawn t the RIGHT! Aldses cntain an aldehyde grup Have 1-4 chiral centers per mlecule Be familiar with bth pen chain & ring frms Knw structures f glucse

2 2 D-glyceraldehyde L-glyceraldehyde Ketses Structures based n dihydrxyacetne (simplest ketse) D is determined by the asymmetric carbn FURTHEST AWAY frm the ketne and is drawn t the RIGHT! Cntain a carbnyl grup Have 1,2 r 3 chiral carbns per mlecule Knw the structures f ribulse & fructse Nmenclature dihydrxyacetne The number f carbns are indicated by the prefix fr the sugar such that hexses (e.g., glucse and fructse) cntain 6 carbns and pentses cntain 5 carbns. trise 3 tetrse 4 pentse 5 hexse 6 heptse 7

3 3 Carbhydrates are rich in stereismerism Enantimers = ismers that are perfect mirrr images (i.e., D- and L- glyceraldehyde) Diastereismers = nt mirrr images (i.e., D-erythrse and D-threse) Epimers = ismers that differ at a single asymmetric carbn --- Hexse examples Glucse vs mannse at carbn 2 Gucse vs galactse at carbn 4 CONFIGURATIONS OF CARBOHYDRATES: Asymmetric carbns are thse which have fur different chemical grups attached. Glucse has fur different asymmetric carbns (#2,3,4,5). Lk at epimers f glucse Allse, altrse, and mannse Carbns in sugars are numbered beginning at the end nearest the aldehyde r ketne grup. The "D" r "L" designatin fr a sugar designates the arrangement f the atms arund the asymmetric carbn farthest frm the aldehyde r ketne. Mst sugars in humans are D-sugars.

4 4 Anmeric carbn is the new asymmetric carbn frmed when an alchl (COH) grup in a mnsaccharide reacts with the aldehyde r ketne t frm a cyclic cmpund. The anmeric carbn can either be α r β, depending n the rientatin f the alchl grup n the anmeric carbn relative t the CH 2 OH grup. Glucse frms a 6-membered pyranse ring cnsisting f 5 carbns and 1 xygen. Fructse frms a 5-membered furanse ring cntaining ne less carbn.

5 5 Fund in fruits In slutin, mnsaccharides (aldses & ketses) with 5 r mre carbns are mst stable in their "ring" frm In the ring frm, the carbnyl carbn becmes cvalently bund t anther OH-grup within the chain. Carbnyl carbn becmes the "anmeric" carbn after cyclizatin Mst cmmn ring structures Frmatin f hemiacetals and hemiketals Frmatin f the tw cyclic frms f D- glucse pyranse ring - 6-membered ring (5- r 6-carbn mnsaccharides)(see figure with glucse ring frmatin abve) Glucse = six-carbn aldse C-1 reacts with C-5 OH t frm pyranse ring Cnfrmatin f hydrxyl n carbn 1 α (belw plane f ring) β (abve plane f ring) Cnfrmatinal frmulas f pyranses Pyranses and furanses

6 furanse ring - 5-membered ring (mst 5-carbn mnsaccharides) Fructse = six-carbn ketse C-2 reacts with C-5 OH t frm furanse ring C-1 reacts with C-5 OH t frm pyranse ring Cnfrmatins Anmers r Anmeric

anmeric carbn abve the plane f the ring in glucpyranse The β frm (β-d glucpyranse) is the preferred frm (62%), with α-d-glucpyranse accunting fr the remaining 38%.

6 6 furanse ring - 5-membered ring (mst 5-carbn mnsaccharides) Fructse = six-carbn ketse C-2 reacts with C-5 OH t frm furanse ring C-1 reacts with C-5 OH t frm pyranse ring Cnfrmatins Anmers r Anmeric Carbn = After cyclizatin, the anmeric OHgrup can be abve, r belw, the plane f the ring α-d sugars have the OH-grup n the anmeric carbn belw the plane f the ring β-d sugars have the OH-grup n the anmeric carbn abve the plane f the ring in glucpyranse The β frm (β-d glucpyranse) is the preferred frm (62%), with α-d-glucpyranse accunting fr the remaining 38%. α and β frms intercnvert in water thrugh straight-chain frms(mutartatin) D-glucse in slutin is 1/3 α and 2/3 β (1% pen chain) - these are anmers Chair vs bat frm f pyranse ring Mnsaccharides are reducing agents Sme hexse derivatives imprtant in bilgy

7 7 Tllens Reagent Benedict Reagent Sugars as reducing agents After entering a cell, sugars are immediately phsphrylated by additin f phsphate usually derived frm ATP. Such phsphrylated sugars are key intermediates in metablic pathways and can interact in electrstatic interactins One imprtant reasn fr phsphrylating sugars is t prevent them frm leaving the cell. Phsphate grups accmplish this because they have a high negative charge assciated with them readily crss cell membranes. Sme phsphrylated sugars are highly reactive and can transfer phsphate t ADP t frm ATP. Cmplex Carbhydrates Hw are the mnmers linked tgether? Use the chemistry f hydrxyl and carbnyl grups -O- Glycsidic bnds (xygen) analg f the peptide bnd = remval f water n mutartatin since pening and re-clsing f the ring frm n lnger pssible brken dwn by glycsidases via additin f water Disaccharides Tw mnsaccharides jined by a O-glycsidic bnd Glycsidic bnd - catalyzed by hydrlase (dehydratin reactin) t frm R-O-R linkage Glycsidic bnds hld tgether the mnsaccharides in a plysaccharide. The bnd is frmed when the anmeric hydrxyl grup cndenses with an alchl grup n a secnd mnsaccharide.

8 Anmeric OH-grup frm ne sugar reacts with an OH-grup n anther sugar Reactin generally leaves ne "anmeric" carbn Disaccharides cmmn in nature Sme cmmn disaccharides sucrse - disaccharide cntaining

8 8 Anmeric OH-grup frm ne sugar reacts with an OH-grup n anther sugar Reactin generally leaves ne "anmeric" carbn Disaccharides cmmn in nature Sme cmmn disaccharides sucrse - disaccharide cntaining fructse + glucse linked via an α (1- >2) linkage (n free anmeric carbn) glucse α (1->2)-β-fructse alpha-d-glucpyransyl - (1-->2) - beta-d-fructfuranside lactse (milk sugar) - a disaccharide cnsisting f galactse + glucse linked by a β (1->4) linkage (free anmeric carbn) - galactse β (1- >4)glucse β -D-galactpyransyl - (1-->4) - α-d-glucpyranse Lactse intlerance In the intestine lactase hydrlyzes lactse, a disaccharide, t galactse and glucse by cleaving a ß-1,4-galactsidic bnd. Apprximately ne in 4 adults is deficient in this enzyme leading t lactse intlerance. Up t 90% f Asians and Africans may be lactasedeficient as adults. Lactse accumulates in the intestine due t pr absrptin. Bacteria prduce metablites f lactse leading t fluid influx int the intestine. Clinical symptms include distensin, nausea, cramping, watery diarrhea. Lactse must be remved frm the diet.

9 9 maltse - 2 glucpyranse units jined by an α (1->4) linkage (free anmeric carbn) α frm - glucse α (1->4)- α -glucse β frm - glucse α (1->4)-β-glucse α -D-glucpyransyl - (1-->4) - α -D-glucpyranse Oligsaccharides mnsaccharides linked by glycsidic bnds Plysaccharides (glycans) - plymers f mnsaccharides (8 r mre) linked by glycsidic bnds. In cntrast t the ther bimlecules, sugars can frm branched as well as linear plymers. Sugar plymers f high mlecular weight (can be ver 10 6 residues)(dextrans are α -1,6 bnds) Amylse and amylpectin, the plysaccharide f starch Strage (energy) Hmplysaccharides - plysaccharides cmpsed f nly ne type f sugar invlved Starch (plants) - cnsists f tw types f glucse hmplysaccharides (strage frm f glucse) Structural frms α -amylse - α (1->4) linked glucpyranse plymer Unbranched, irregular helical ciled cnfrmatin Amylpectin - α (1->4) glucpyranse plymer with α (1->6) branch pints Branches ~ every 30th bnd Up t 10 6 residues Starch is plant primary fd reserve and is depsited in insluble granules Breakdwn f dietary starch in mammals enzyme α-amylase (in saliva and pancreas) breaks internal α -1,4 linkages t give maltse, malttrise, and α -dextrin (α 1,6's and α 1,4's) chain length reduced frm 1000s t 8 glucse residues we cannt cleave α (1->6)

10 10 Glycgen (animals) - strage frm f glucse in cytplasm f mst cells, but particularly high in liver & skeletal muscles f animals (stred as granules) Glycgen is similar t amylpectin, but mre highly branched α (1->4) linked glucpyranse plymer with α (1->6) branch pints ~ every 10th bnd Glycgen requires tw enzymes fr degradatin One t hydrlyze α (1->4 linkages (α -amylase in digestive system r glycgen phsphrylases in cells) One t hydrlyze α (1->6) linkages (debranching enzyme in cells) Glycgenlysis in liver and release f free glucse int bld stream when bld glucse drps Glycgenesis in liver when bld glucse is high by transprt f glucse int liver and synthesis f glycgen Structural hmplysaccharides Cellulse (plants) - β (1->4) linked glucpyranse plymer - ne f the mst resistant natural plymers made plant cell walls maintains shape withstands smtic pressure changes as many as 15,000 D-glucse residues linked by β-1,4 linkages (we can't digest this linkage) ruminants have prtza and bacteria that cntain cellulase (mutualistic symbisis) unbranched - gives straight chain stabilized by hydrgen bnds makes lng fibrils with high tensile strength

11 11 Chitin (invertebrate exskeletn) - β (1->4) linked N-acetylglucsamine plymer Therefre, like cellulse except N-acetyl grup at C-2 in residues Cell walls f fungi & algae are als a plymer f N-acetylglucsamine with β 1,4 unbranched linkages - is very strng Plysaccharides cmpsed f tw r mre types f mnsaccharide units Gycsaminglycans cnsist f repeating disaccharide units with negatively charged grups Many are linked t prteins and are knwn as prteglycans Imprtant in cnnective tissue, basement membrane, synvial fluid f jints, and in the extracellular matrix between cells -- Examples Hyalurnic acid r hyalurnate β (1->3) linked glucurnic (COOH in 6 psitins) and N- acetyl-d-glucsamine plymer Chndritin 6-sulfate Heparin (anticagulant)

12 12 Keratin sulfate Peptidglycan

13 13 OTHER COMPLEX CARBOHYDRATES Prteglycan structure f an integral membrane prtein A prteglycan aggregate f the extracellular matrix

14 Oligsaccharide linkages in glycprteins Interactins between cells and extracellular matrix Glycprteins ---> CHO residues n Prteins = Invlved in Cell Recgnitin/Cell Adhesin

Disaccharide cre f galactse β 1,3 N-acetylgalactsamine Can be branched CHO frm this basal unit N-glycsylatin = Plysaccharides are attached t asparagine R-grup amine frming

14 14 Oligsaccharide linkages in glycprteins Interactins between cells and extracellular matrix Glycprteins ---> CHO residues n Prteins = Invlved in Cell Recgnitin/Cell Adhesin Mdified mnsaccharides (fucse and sialic acid) are ften attached at β bends r β-turns O-glycsylatin = Plysaccharides are attached t serine r thernine OH frming -O-glycsidic bnds Disaccharide cre f galactse β 1,3 N-acetylgalactsamine Can be branched CHO frm this basal unit N-glycsylatin = Plysaccharides are attached t asparagine R-grup amine frming -N-glycsidic bnds N-acetylglucseamine is the first sugar in the unit with branched CHO attached N-linked carbhydrates have a cmmn cre: Anther carbhydrate fund n prteins is sialic acid

15 Cmmn linkage is -gal-sia by an α - 2,3 linkage Pssible rle f sialic acid: prtein recycling New prteins in bld fr example, immunglbins and sme hrmnes, are synthesized with sialic acids present.

15 15 Cmmn linkage is -gal-sia by an α - 2,3 linkage Pssible rle f sialic acid: prtein recycling New prteins in bld fr example, immunglbins and sme hrmnes, are synthesized with sialic acids present. With time, sialic acids are remved (sialidase). Enzyme recgnized asialglycprtein, binds it, and takes it up int liver cells where it is digested. Other rles include: cell binding cell-cell recgnitin Nucletide-linked Sugars UDP-glucse Bacterial Lippsaccharides

16 16 Definitin: Plyhydrxy aldehydes r ketnes; als called sugars r carbhydrates aldse- made frm aldehyde ketse- made frm ketne

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BIOLOGY 101. CHAPTER 5: The Structure and Function of Large Biological Molecules: The Molecules of Life

BIOLOGY 101. CHAPTER 5: The Structure and Function of Large Biological Molecules: The Molecules of Life BIOLOGY 101 CHAPTER 5: The Structure and Functin f Large Bilgical Mlecules: The Mlecules f Life Structure and Functin f Large Bi Mlecules: Mlecules f Life CONCEPTS: 5.1 Macrmlecules are plymers, built