biochemistry of carbohydrates

8/11/2019 Biochemistry of Carbohydrates

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Marco Perikar R. Dimaano 1BMed Class 2015

BIOCHEMISTRY OF CARBOHYDRATESUST FMS

General Formula : Cx(H2O)y or (CH2O)nCarbon compounds having Carbonyl Carbon (C=O) and hydroxyl (-OH) functional groupsCarbonyl Functional Groups :

Aldehyde (Pol yhydroxyaldehydes): 1 st C (C=O) Ketone (Polyhydroxyketones): 2 nd C (C=O)

Classification1) Size of base Carbon chain

Triose (3C), Tetrose (4C), Pentose (5C), Hexose (6C), Heptose (7C), Nanose (9C)2) Number of sugar units

Monosaccharide 1 CHO unit Disacchar ide 2 CHO units Oligosaccharide 3-10 CHO units Polysacchari de >10 units

3) Location of Carbonyl carbon Aldose Ketose

Nomenclature

*Aldohexoses: ALL ALTruists GLadly MAke GUm IN GALlon TAnk.2 nd C: alternate OH3 rd C: alternate OH by 24 th C: 1st 4 Right OH, Last 4 Left OH5 th C: all OH at right side Ketoses

Ketotriose

Ketotetrose

Ketopentose

Ketohexose

Aldotriose

Aldotetrose

Aldopentose

Aldohexose


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Fischer Projection Sugars drawn in straight chain

Perspective structural formula : 3D FisherHaworth Projection

Cyclic forms which show the molecules as cyclic andplanar with substituents above or below the ring

Boat and Chair conformation : more plausible bent forms Fischer projection Haworth projection

Optical Activity

Ability to rotate plane of polarized light All CHOs contain assymetrical (chiral) carbon and are, therefore,optically active .a. Dextrorotatory (+) : D isomer

o Rotates to righto In Fischer, -OH is at the right side of penultimate Carbono In Haworth, last Carbon is above the ring

b. Levorotatory (-) : L isomer

o Rotate to lefto In Fi scher, -OH is at the left side of penultimate Carbono In Haworth, last Carbon is below the ring

*Assymetric or Chiral Carbon : carbon with 4 different substituents*Penultimate Carbon : chiral carbon farthest from functional group

StereochemistryIsomers : same molecular formula and bonds but differ in spatial arrangement

A. Constitutional Isomers Different a tom connectivities

B. Stereoisomers Same a tom connectivi ty, different spatia l arrangement 2 types: Configurational and Conformational

1. Configurational Isomerso Interconverted only by breaking covalent bonds (separa ble)o 4 types: Enantiomer, Diastereomer, Epimer, Anomer

a.

Enantiomer Stereoisomers which are non-superimposable mirror images of eachother (Eg. D-glucos e and L-glucos e)

b. Diastereomer Stereoisomers which are non-superimposable non-mirror images of

each other (Eg. D-gal actose and D-glucose)

c. Epimer Stereoisomers which differ in one stereocenter (different -OH

position al ong 1 Carbon atom only) Example: D-glucose, D-mannose and D-galac tose

d. Anomer Stereoisomers which differ only i n the configurati on around the

carbon (anomeric carbon, usually C1) which was involved in theintramolecular nucleophili c attack (Eg. and anomers )

Fischer Projection:anomer (Cis): OH of anomeric Carbon and hemibridge on sa me side

anomer (Trans): OH of anomeri c Carbon and hemibridge on opposite s ideHaworth Projection:

anomer (Trans ): C6 up, -OH of C1 (anomeric ca rbon) down if in D isomer

C6 down, -OH of C1 (anomeric carbon) up if in L isomer

anomer (Cis): C6 up, -OH of C1 (anomeric carbon) up if in D isomer

C6 down, -OH of C1 (anomeric carbon) down if in L isomer*Mutarotation : and are in equilibrium


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2. Conformational Isomerso Related by rotation around single bond (bending

and twisting)o Interchange without breaking covalent bondso Boat and Chair conformationa. Boat conformation : less stable due to steric

hindrancesb. Chair conformation : more stable*Axial Bond : perpendicular to plane*Equatorial Bond : parallel to plane

Monosaccharides

Glucose Central sugar in metabolism Can cycl ize through intermolecular nucleophil ic attack of one of

the OHs on the Carbonyl Carbon of the aldehyde Occurs if stable 5 or 6 member rings can form Furanose (5 member) or Pyranose (6 member) On nucleophilic attack to form the ring, carbonyl O becomes an OH

Fructose : 67% pyranose, 33% furanoseRibose : 25%pyranose, 75% furanose* Glucose is exclusively pyranose. Fructose and Ribose a re exclusively furanose.

Monosaccharide Derivatives

1. Sugar Acids Oxidized forms in which a ldehyde and/or al cohol functional groups are oxidized to carboxylic acid ( Oxidation)

a. Aldonic Acido Aldehyde group is oxidi zed (Eg. Gluconic Acid)

b. Uronic Acido Terminal a lcohol i s oxidized (Eg. Glucuronic Acid )

c. Aldaric Acido Both aldehyde and terminal alcohol are oxidized

2. Sugar Alcohol Reduction of Carbonyl group to OH ( -ol) (Eg. Dulcitol:excess causes cataract in galactosemia patients)

3. Phosphorylated Sugar Phosphate is added by ATP forming phosphoester

derivatives Eg. Glucose-6-Phosphate Glucose-6-Phosphate

4. Amino Sugars Amino group replaced hydroxyl group (-OH to -NH) Eg. Glucosamine, Galactosamine

5. Acetylated Amine Derivative Sugars derived from amino sugars

Eg. N-acetylglucosamine, N-acteylgalactosamine 6. Lactone Forms Intramolecular esters Hydroxyl group attacks Car bonyl carbon that was previously oxidized

to Carboxylic acid (Eg. Gluconolactone) 7. Deoxysugars

One or more Carbon atoms have been reduced, losing hydroxylgroup (-OH to -H) (Eg. Deoxyribose)


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8. Condensation Products of Sugar Derivatives with Lactate and Pyruvate Forms Muramic Acid (glucosamine + lactic acid) Forms Neuraminic Acid (mannosamine + pyruvic acid) N-acetylmuramic Acid (MurNAc or NAM): GlcNac + la ctic a cid (ether link at C3)

o found in bacterial cell walls Sialic Acids :

o Found on surface of all cells o Involved in cell contact/communication o Involved in recognition bacteria ( cholera) and vir uses (influenza) o N-acetyl-neuraminic Acid (NANA):

N-acetylmannosamine (ManNac) + pyruvic acid found only in humans lack hydrolase gene (92 base pairs of gene missing)

o N-glycoyl-neuraminic Acid: N-glycoylmannosamine + pyruvic acid Have hydroxylase

Neuraminic Acid

Oligosaccharides

Polysaccharides

Homopolysaccharides : polysaccha rides with 1 type of repeating monosaccharide unit Starch : found in plants; composed of:

o Amylose (20%) Linear chain of Glc in 1-4 links (or repeating maltoses)

o Amylopectin (80%) Branched chain i n 1-6 links

o Major part: Glc chain of 24-30 units (amylose) then branchesoff (amylopectin)

Glycogeno Main carbohydrate storage in animals o Composed of Glc residues in 1-4 links and 1-6 branches

(greater than starch) o Synthesized on Glycogenin protein primer o Reason why glycogen i s s tored rather than glucose: Has l ess osmotic pressure than glucos e, therefore, does not easi ly

reacts with water o Source: Muscles (greatest s ource in terms of total glycogen mass source) and li ver (greatest source in terms of grams

glycogen per gram tis sue)


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Celluloseo Linear chain of Glc residues in 1-4 li nks (or repeating cellobiose) o Held together by intra- and inter-chain H-bondso Most abundant biological molecule in nature; cannot be broken

down by humans (l ack of cellula se) Chitin

o Linear chain of GlcNAc in 1-4 links Heteropolysaccharides : polysaccha rides with 2 different monosaccharide unitsComplex Oligosaccharide Units

Mucopolysaccharides/Glycosaminoglycans (MPS/GAG) o Amino sugar + negatively charged sulfate or

carboxyl group (uronic acid: glucuronic or iduronicacid)

o Form matrix to hold protein component of skin,connective tissue and extracellular matrix

o Often covalently attached to proteins to formproteoglycans

o Hyaluronic Acid Hyaluronic Acid Dermatan Sulfate Glucuronate( 1-3)GlcNAc Water s oluble; found in synovial fluid Backbone for attachment proteins

o Dermatan Sulfate L-Iduronate( 1-3)GalNAc-4-Sulfate

o Chondroitin Sulfate D-Glucoronate( 1-4)GalNAc-4or6-Sulfate

o Heparin D-Glucoronate-2-Sulfate( 1-4)GlcNSulfo-6-Sulfate Chondroitin Sulfate Heparin Antithrombin, naturally-occurring anticoagulant

o Keratan Sulfate D-Gal(1-4)GlcNAc-6-Sulfate No uronic acid component

o Syndecan Heparan Sulfate Binds through intracellular domain to the cytoskeleton Interacts with fibronectin

o Glypican Heparin Keratan Sulfate Attached to outer s urface of plasma membrane via

phosphatidyl i nositol lipid Peptidoglycans

o Bacterial Cell Walls Offer protection from hypotonic condition and high i nternal osmotic

pressure Long chain of GlcNAc(1-4)MurNAc (NAG,NAM) Gram (+) Bacteria

Multi-layered; cell wall can be Gram stained (violet) Chains are covalently connected by a Pentaglycine Bridge through the

-Amino group of tetrapeptide Lysine on one

strand and D-Alanine on another strand Teichoic Acid Alternating residue of D-Ala a nd NAG in C2 Glycerol

or Ribitol Phosphate backbone Multiple glycerols are linked through Phosphodiester

Bonds Often attached to C6 of NAM Make up 50% of cell wall dry weight Present a foreign antigenic sur face to infected host Serve as receptors for bacteriophages


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Gram (-) Bacteria Cell wall cannot be Gram-stained (red) No pentaglycine bridge; chains are connected by direct amide bond between the -Amino group of

tetrapeptide Lysi ne on one strand and D-Alanine on another stra nd Hydrophobic protein covalently attaches (through Lys amide bond) to the last amino acid in the tetrapeptide

unit of cell wall (actuall y diaminopimeli c aci d/DAP, which replaces 10% of D-Ala in cell wall) No teichoic aci d; Cell wall sandwiched between l ipid bil ayer; Periplasmic space space between lipid bilayers Lipopolysaccharide (O antigen) coats the outer membrane and determines a ntigenic ity of bacteria

Proteoglycanso GAG covalently O-linked to protein (usually to Ser residue

of Ser-Gly di peptides)o May contain N-linked oli gosaccharide groupso Carbohydrates > Proteinso Solubleo CHO part provides an incredible variety of binding

structures (acts linke glue) in connecting intra- andextracellula r cell functions

o Syndecan : protein + heparin sulfate + chondroitin sulfate;binds through its intracellular domain to the internalcytoskeleton of the cell while interacting with fibronectinin the extracellular matrix

o Aggrecan : protein + Chondroitin sul fate + Keratan sulfate; binds hyal uronic ac id; important in hydration of cartila geso Versican : protein + Chondroitin sul fate; binds hyaluronic aci d in extracell ular matrix

Glycoproteins/Glycosylated Proteinso Proteins post-transla tional ly modified by attachment of carbohydrateso Usual ly attached through either Asn or Ser side chainso Involved in recognition of binding molecules, prevention of aggregation

during protein foldi ng, protection from preoteolys is , increase in proteinhalf-life, blood clotting, immunologic protection and ABO blood groups.

o N-linked glycoproteins Carbohydrate a ttached to either GlcNAc or GalNAc to an Asn in a X-

Asn-X-Thr sequence of protein Core oligosaccharide: (Man) 3(GlcNAc)2 attached to Asn 3 types: Mannose, Complex, Hybrid

o O-linked glycoproteins Carbohydrate usually attached from a Gal( 1-3)GalNAc to a Ser or

Thr of a protein Eg. Blood Group Antigens

Storage Polysaccharides : Starch, GlycogenStructural Polysaccharides : Cellulose, Chitin, GAGs, Peptidoglycans


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Hemiacetal and Hemiketal Formation

Aldehyde or ketone group of monosaccha rides can cyclize through intramolecular nucleophil ic a ttack of a hydroxyl group ( -OH)at the Carbonyl car bon in an addition reaction forming Hemiacetal or Hemiketal, respectively.

On addition of acid: anomeric OH is protonated, forming water, a leaving group Another al cohol ca n be added forming Acetal or Ketal

Reducing Property of Sugars

Reducing Sugars: sugars which can form an aldehyde at C1 or have an -hydroxymethyl ketone group which ca n i somerizeto an a ldehyde under bas ic conditions, such as fructoseo Eg. All common monosaccharides, maltoseo Eg. Lactose: Since Glc is attached through the OH on C4, its anomeric carbon could revert to noncyclic aldehyde form,

which is susceptible to oxidation , thus, subsequently reduced. Non-Reducing Sugar : sugars in which there are no aldehyde or ketone group to react; sugar rings are locked or not capable

of openingo Eg. Sucrose: Since the anomeric carbons of both Glc and Fru are linked, it cannot be reduced (neither of the rings can

be opened). Tests for identifying Reducing Sugars:

o Benedicts : Copper Sulfate + Alkaline Citrate; deep blue brick red ppto Fehlings : Copper Sulfate + Alkali ne Tartra te; deep blue brick red ppto Tollens : Sil ver Nitrate + Aqueous Ammonia; colorless silver mirror

biochemistry of carbohydrates

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