02 02. Carbohydrates

8/20/2019 02 02. Carbohydrates

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CARBOHYDRATES


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compound that consists only of Carbon,Hydrogen and Oxygen

Saccharide which comes from the Greekword sákkharon, meaning "sugar"

most abundant biomolecules on earth

Divided into Monosaccharides,Disaccharides, Polysaccharides and

Oligosaccharides Widely distributed in plants and animals

Glucose is the most importantcarbohydrate


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Major metabolic fuel of mammals anduniversal fuel of the fetus

Oxidation of carbohydrates as a source ofenergy

Structural and protective elements in theconnective tissue of animals

Participate in recognition and adhesion of cells

Determine the metabolic fate of proteins andlipids when attached to them

Structural elements of nucleic acids andcoenzymes


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Outside of the body, glucose exists in itsstraight chain form.

In this form, the carbon atoms are

bound together in a long chain, with thehydrogen and oxygen atoms bound ateither end and along the sides.


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Within a living organism --humans, plants, or animals --

glucose exists in a ring thatresembles a hexagon

This cyclic structure isfavored on thermodynamicground


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These two forms often coexist

rings can open and re-close

Anomeric carbon- carbon about whichrotation occurs

two forms are termed Anomers


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Furanose and Pyranose forms exist in

equilibrium with the straight-chain form.

Two conformations

› chair form and the boat form. chair form is

more stable Constituents of the ring

› project above or below the plane- axial

›

project parallel to the plane- equatorial.


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Monosaccharides - cannot behydrolyzed into simpler carbohydrates

According to number of Carbon atoms

Trioses

Tetroses Pentoses

Hexoses

Heptoses

Nonoses

© Lippincot Biochemistry, 3rd ed.


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Monosaccharides - cannot behydrolyzed into simpler carbohydrates

According to functional group attached Aldose

Ketose• Polyhydric alcohols/

Sugar alcohols/ Polyols

© Lippincot Biochemistry, 3rd ed.


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Disaccharides - condensationproducts of two monosaccharide units

eg. Maltose (glu+glu), sucrose (glu+fru)

Oligosaccharides - condensationproducts of three to ten

monosaccharides-Most are undigested by humanenzymes


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Polysaccharides - condensation productsof more than ten monosaccharide units According to identity of constituent

monosaccharides Hexosans Pentosans

eg. starches, dextrins (linear/branched polymers) Nonstarch polysaccharides – not digested by human

enzymes- major component of dietary fiber- eg. cellulose (plant cell wall, glucose polymer);

inulin(storage carbohydrate in some plants, fructosepolymer)


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CARBOHYDRATE Disaccharides

Polysaccharides

Oligosaccharides

Identity ofconstituent

monosaccharides

Hexosan

Pentosan

Monosaccharides

No. of

Carbonatoms

Tetrose

Pentose

Heptose

Hexose

Triose

Functional

groupattachment

Aldose

Ketose

Classification accg. to Harper’s Illustrated Biochemistry, 28th ed.


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Isomers are compounds with thesame molecular formula butdifferent chemical structures.

Isomers do not necessarily share similarproperties, unless they also have thesame functional groups.

There are 2 main forms of Isomerism:Structural Isomerism and Stereoisomerism.


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In structural isomers, sometimes referredto as constitutional isomers, the atomsand functional groups are joined

together in different ways. Differ in the order in which the atoms are

connected.

Structural isomers havedifferent IUPAC names and may or maynot belong to the same functionalgroup.


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Stereoisomers are isomericmolecules that have the samemolecular formula and sequence of

bonded atoms (constitution), but thatdiffer only in the three-dimensionalorientations of their atoms in space.

Number of possible isomers depends on(n), number of asymmetric carbonatoms, = 2.


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Can be interconverted exclusively byrotations about formally single bonds

Interconversion necessarily involves

breaking and reforming of chemicalbonds


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Rotamers

› Specific type of conformational isomers

› When the rotation leading to different

conformations is restricted (hindered)rotation

› There exists a rotational energy barrier thatneeds to be overcome to convert one

conformer to another


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Stereoisomers that do not readilyinterconvert at room temperature and

can be separated. Geometric and Optical


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Geometric

› Configurational isomers that differ in the

spatial position around a bond withrestricted rotation (e.g. a double bond)

› Cis-trans and E-Z Conformation


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Cis-trans

› in which cis means "on the same side"

› Trans means "on the other side" or "across".

› not effective when there are more than twodifferent substituents on a double bond


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E-Z

› E isomer:

If the two groups of higher priority are on

opposite sides of the double bond (from entgegen the German word for

"opposite").

› Z isomer:

If the two groups of higher priority are on thesame side of the double bond

(from zusammen, the German word for"together").


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E-Z


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Configurational isomers that differ in the3D relationship of the substituents aboutone or more atoms.

Divided into:› Enantiomers

non-superimposable mirror images

›

Diastereomers Not enantiomers


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Have identical chemical and physicalproperties

Except for their ability to rotate plane-polarized light (+/−) by equal amounts but

in opposite directions Racemic mixture

› A mixture of equal parts of an optically activeisomer and its enantiomer

› has zero net rotation of plane-polarizedlight because the positive rotation of each (+)form is exactly counteracted by the negativerotation of a (−) one.


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R- and S- If the center is oriented so that the lowest-

priority of the four is pointed away from a

viewer, two possibilities:› If the priority of the remaining three

substituents decreases in clockwise direction, itis labeled R (for Rectus, Latin for right),

› if it decreases in counterclockwise direction, itis S (for Sinister , Latin for left).


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By optical activity: (+)- and (−)- or d- and l-› direction in which it rotates the plane of polarized

light

› (+) or d: rotates the light clockwise, dextrorotatory

›

(-) or l: rotates light counterclockwise, levorotatory By configuration: D- and L-

› by the spatial configuration of its atoms byrelating the molecule to glyceraldehyde

›

COOH → R → NH2 → H,› D: groups are arranged clockwise around the

carbon atom

› L: groups are arranged counterclockwise aroundthe carbon atom


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Asymmetric Carbon› carbon atom that is attached to four different

types of atom or four different groups of atoms

Optical Activity or Optical Rotation› turning of the plane of linearly polarized light

about the direction of motion as the light travelsthrough certain materials

Reference Sugar› Glyerose or glyceraldehyde

› Parent compound of the carbohydrate family

› Basis for D and L isomerism


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Epimers

› are diastereomers that differ in configurationof only one stereogenic center

Anomers› also called anomeric carbons

› special type of epimer

›

It is one of two stereoisomers of a cyclicsaccharide that differs only in itsconfiguration at the hemiacetal or hemiketalcarbon


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Change in the optical rotation that occursby epimerization (that is the change in theequilibrium between two epimers, when

thecorresponding stereocenters interconvert)

Cyclic sugars show mutarotation as α andβ anomeric forms interconvert

The optical rotation of the solutiondepends on the optical rotation of eachanomer and their ratio in the solution.


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Determined by its spatial relationship toglycerose (glyceraldehyde)

Orientation of H and OH groups around

the carbon atom adjacent to theterminal primary alcohol carbon

› D isomer : OH on the right side

›

L isomer: OH on the left side Most monosaccharides in mammals are

in D form


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Presence of asymmetric carbon atomsconfers optical activity on the compound

› Dextrorotatory or (+): light rotated to the right

›

Levorotatory or (-): light rotated to the left A compound may be designated D(-),

D(+), L(-) or L(+),

Naturally occurring form of fructose is D(-)

Racemic mixture – equal amounts of D andL isomers, no optical activity


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Based on the fact that the stable ringstructures of monosaccharides are similarto the ring structures of either pyran orfuran

Ketoses may also show ring formation(fructofuranose and fructopyranose)

More than 99% of glucose is in thepyranose form


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Ring structure of aldose is hemiacetal(formed by aldehyde and alcohol)

Ring structure of ketose is hemiketal (ketone

and alcohol) Crystalline glucose is α-D-glucopyranose

In solution: α-glucopyranose (38%), β-glucopyranose (62%)

Equilibriation is accompanied by opticalrotation as the hemiacetal ring opens andreforms with the change of H and OH on C1


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The optical rotation of glucose in solution is

dextrorotatory, hence the name dextrose.


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Result in variations in configurations ofthe OH and H on Carbon 2,3,4 ofglucose

Most important epimers of glucose are

› Mannose (epimerization at carbon 2)

› Galactose (epimerization at carbon 4)


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Fructose and glucose

› Same molecular formula differs in structure

Potential keto group in position 2 offructose

Potential aldehyde group in position 2 ofglucose


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Sugars may be represented by theformula CnH2nO

Acyclic mono and disaccharidescontain aldehyde groups or ketonegroups

These groups contain C=O where onemay find its reactivity


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Saccharides with a ring greater than onein their structure is formation from two ormore monosaccharieds joined by abond called glycosidic bonds. This resultsa to a loss of a molecule of water perbond.


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Carbohydrates that cannot behydrolyzed into simpler carbohydrates

May be classified as trioses, tetroses,pentoses, hexoses, heptoses (# of Catoms)

May be classified as aldose (aldehydegroup) or ketose (ketone group)


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Two of the most commonmonosaccharides are glucose and

fructose. Both glucose and fructose havethe same chemical formula (C6H12O6);however, they have different structures,

as shown.


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Glucose is the most important carbohydrate

Dietary sugar absorbed in the bloodstream Other sugars converted to glucose in the liver

Major metabolic fuel in mammals

Precursor for synthesis of all othercarbohydrates in the body› Glycogen for storage

› Ribose and deoxyribose in nucleic acids

› Galactose in lactose of milk

› Glycolipids

› Glycoproteins and Proteoglycans


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• Sugars formed by linking 2mono-saccharide units by

glycosidic bond• Formed by dehydration

synthesis

DISACCHARIDES


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DISACCHARIDES

SUCROSE


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SUCROSE

COMPOSITION O-α- glucopyranosyl- (1-->2)-β- D-fructofuranoside

STRUCTURE

SOURCE Cane and beet sugar, sorghum and some fruitsand veg

CLINICALSIGNIFICANCE

Rare genetic lack of sucrase leads to sucroseintolerance — diarrhea and flatulence

MALTOSE


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MALTOSE

COMPOSITION O-α-glucopyranosyl- (1-->4)-α-D-glucopyranose

STRUCTURE

SOURCE Enzymic hydrolysis of starch (amylase)Germinating cereals and malt

CLINICALSIGNIFICANCE

LACTOSE


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LACTOSECOMPOSITION O-α- galactopyranosyl- (1-->4)-β-D-

glucopyranose

STRUCTURE

SOURCE Milk (and many pharmaceutical preparations as

filler)CLINICALSIGNIFICANCE

Lack of lactase (alactasia) leads to lactoseintolerance — diarrhea and flatulence

May be excreted in the urine in pregnancy


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polymers made up of manymonosaccharides joined together byglycosidic bonds by condensation

reaction


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Based on Structure:

1. homo-polysaccharide - only one typeof monosaccharide repeating in thechain

2. hetero-polysaccharide - composed of

two or more types of monosaccharides


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Based on Function

1.Structural – cellulose, chitin

2. Storage – energy sources:glycogen, starch


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Chief constituent of plant cell walls

linear chain of several hundred to over tenthousand β(1→4) linked D-glucopyranoseunits

multiple hydrogen bonds is responsible forthe high tensile strength or rigidity


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chain of α – D-glucopyranose residues in

a (α1→4) bond with branching by(α1→6) bond synthesized from monomers of UDP-

glucose by the enzyme glycogen

synthase

amylo (α1→4) to (α1→6)transglycosylase

- glycogen-branching enzyme


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R

Nonreducing ends

Glucose residue linked by -1,4Glucose residue linked by -1,6

R Reducing end attached to glycogenin


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occurs mainly in the cytosol of liver cells andmuscles.

Requires: primer – already existing short chains of glucose Initiator – Glycogenin ( a protein with tyrosine

residue which serve as site at which initial glucoseunit is attached)

- required when the glycogen stores aredepleted

UDP-Glu units (Uridine diphosphate glucose units). Two enzymes:

Glycogen synthase Branching enzyme


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4 Steps:

Synthesis of UDP-glucose

Synthesis of a primer to initiate glycogensynthesis

Elongation of glycogen chains byglycogen synthase

Formation of branches in glycogen


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Glucose + ATP Glucose 6- + ADP

Hexokinase (per ipheral tissue)

Glucokinase (l iver)P

Glucose 6- Glucose 1-Phosphoglucomutase

PP

Glucose 1- + UTP UDP-glucose + PPiP

UDP- Glucose

pyrophosphorylase


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UDP

Glycogenin

Primer

UDP Glu

Glycogen synthaseUDP

UDP

Glu

R

R

Elongatedbranchof glycogen

Branching enzyme

Formation ofnew branches

R


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stored in the liver and muscles main form of stored carbohydrate in the body

ENZYME HORMONE

Glycogen

formation

Glycogen

synthase

insulin

Glycogen

breakdown

Glycogen

phosphorylase

glucagon


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insulin

hypoglycemia glycogen

accumulation

insulin diabetes glycogen

depletion

•glycogen storage diseases - inborn errorsof metabolism are caused by deficiencies

of enzymes necessary for glycogen synthesisor breakdown (ex. von Gierke's Disease (type IA) – glucose-6-phosphatase deficiency)


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Liver – maintains blood glucoseconcentration at normal levels

Skeletal muscle – fuel reserve for ATPsynthesis needed for muscle contraction


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Homopolymer of glucose forming aglucosidic chain (glucosan/glucan)

Linear Amylose (13-20%) and branchedAmylopectin (80-85%)

Branched chains of 24-30 glucoseresidues united by (α1→4) bonds withbranching by (α1→6) bonds


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Found in naturally occurringpolysaccharides produced by many typesof plants that use it as a means of storingenergy; found in roots or rhizomes

polymers composed mainly of fructose units joined by a β(2→1) glycosidic bond

used clinically as a highly accuratemeasure of glomerular filtration rate (the

flow rate of filtered fluid through the kidney) it is completely filtered at the glomerulus

but neither secreted nor reabsorbed by thetubules


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low-molecular-weight carbohydratesproduced by the hydrolysis of starch

polymers of D-glucose units linked by α-

(1,4) or α-(1,6) glycosidic bonds. Inulin and dextrin are water soluble and

indigestible dietary fiber (prebiotics) that

stimulate the growth and activity ofbacteria in the digestive system whichare beneficial to the health of the body


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Chitin

N-acetyl-D-glucosamine units joined by b1-4 glycosidic bonds


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A derivative of glucose

Main component of the cell walls offungi, exoskeletons of crustaceans and

arthropods etc.May be compared to the

polysaccharide Cellulose (substitute thehydroxyl group on each monomer withan acetyl amine group) and the proteinKeratin (similar structural functions)


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Agriculturea good inducer for defense mechanisms in plants. It wasrecently tested as a fertilizer that can help plants develophealthy immune responses, and have a much better yield andlife expectancy. Chitosan is derived from chitin.

Industrialused as an additive to thicken and stabilize foods andpharmaceuticals. It also acts as a binder in dyes, fabrics, andadhesives. Industrial separation membranes and ion-

exchange resins can be made from chitin. Processes to sizeand strengthen paper employ chitin

MedicineChitin's properties as a flexible and strong material make itfavorable as surgical thread. Its biodegradibility means itwears away with time as the wound heals. Moreover, chitinhas some unusual properties that accelerate healing ofwounds in humans.

Occupations associated with high environmental chitin levels,such as shellfish processors, are prone to high incidences ofasthma. Recent studies have suggested that chitin may play arole in a possible pathway in human allergic disease.


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A linear polysaccharide commercially

produced from the deacetylation of chitin

Used as a Biocontrol elicitor

Has water filtration uses May be used industrially for car paints

Used as a hemostatic agent in bandages

Sold in tablet form at health stores as a fat binder

Studies have shown that chitosan is a solubledietary fiber and alters bile acid composition byincreasing the excretion of sterols and reducingdigestibility of ileal fats


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Also called mucopolysaccharides

Comples carbohydrates containingamino sugars and uronic acids

Attaches to a protein molecule to form aproteoglycan which provide the groundsubstance of connective tissues

Examples of proteoglycans arehyaluronic acid, chondroitin sulfate andheparin


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The synthesis of the core proteins occurs inthe ER but most of the synthesis of gagchains occur in the golgi apparatus

3 major events› Attachment to core proteins

› Chain elongation One enzyme, one linkage relationshio among

nucleotide sugars and glycoslytransferases

› Chain termination Results from sulfation and progression of the growing

GAG chain away from the membrane site of catalysis


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Polymer of disaccharides

Promoter for early inflammation and moderatesthe inflammatory response Helps in tissue repair Molecules that interact with HA has a role in

cancer metastasis (can therefore be used as atumor marker)

Medical applications includes use in eyesurgeries, treatment for osteoarthritis (also hasapplication in racing horses)and atopic

dermatitis Used in skin care products


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Chain of alternating sugars

Usually found in proteins as part of aproteoglycan

An important structural component ofcartilage and provides much of itsresistance to compression

Used as an ingredient of an alternativemedicine to treat osteoarthritis


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Widely used as an injectable coagulant

Does not directly break down clots butprevents them from forming

Used medically to prevent deep veinthrombosis, pulmonary embolism

Widely used in surgeries (e.g coronary bypass for heartsurgery)

Adverse reaction may cause heparin induced

thrombocytopenia


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Both Keratan sulfate I and dermatan sulfateare present in the cornea and presents acritical role in corneal transparency

Dermatan sulfate may play an important role inthe development of atherosclerotic plaquesince arterial smooth muscle cells synthesizethese GAGs

Heparan sulfate is associated with the plasmamembrane of cells, with its core proteinspanning the membrane, acting as receptorsand may also participate in cell growth andcell-cell commuication


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Contains oligosaccharide chains covalentlyattached to polypeptide chains Occurs in most organisms, from bacteria to

humans and even viruses (where they playkey roles such as attachment to cells)

Almost all the plasma proteins in humans(except albumin) are glycoproteins Certain oligosaccharide chains encode

biologic information thus it is of greatphysiologic value to decipher the so called

―sugar code of life‖ which is one of theprincipal aims of glycobiology andglycomics (study of glycomes)

Glycoproteins

Structural molecule Collagen


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Structural molecule Collagen

Lubricant and

protective agent

Mucin

Transport molecule Transferrin, ceruloplasmin

Immunologicmolecule Immunoglobulins,histocompatability

Hormone Chorionic Gonadotropin,tyroid stimulatinghormone(TSH)

Enzyme Various, e.g, alkaline

phosphatase

Cell attachment – recognition site

Various proteins involved in cell-cell(eg sperm oocyte) virus cell


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recognition site cell(eg sperm-oocyte), virus-cell,bacterium-cell, and hormone-cellinteractions

Antifreeze Certain plasma proteins of cold-water fish

Interact with specificcarbohydrates

Lectins, Selectins (cell adhesionlectins), antibodies

Receptor Various proteins involved inhormone and drug action

Affect folding of

certain proteins

Calnexin, Calreticulin

Regulation ofdevelopment

Notch and its analogs, key proteinsin development

Hemostasis (and

thrombosis)

Specific glycoproteins on the

surface membranes of platelets


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Modulate physiochemical properties, egsolubility, viscosity, charge, conformation,denaturation, and binding sites for variousmolecules, bacteria, viruses, and someparasites

Protect against proteolysis, from inside andoutside of cell

Affect proteolytic processing of precursorproteins to smaller products

Are involved in biologic activity, eg, of hCG Affect insertion into membranes, intracellular

migration, sorting and secretion May affect sites of metastases selected by

cancer cells


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O-glycosidiclinkage

N-glycosidiclinkage

Glycosylphosphatidylinosol-

anchored(GPI-

linked)

Involving thehydroxyl side

chain of serine or

threonine and a

sugar such as N-acetylgalactosam

ine eg, Mucin

Involving theamide nitrogen of

asparagine and

N-

acetylglucosamine

Linked to thecarboxyl terminal

amino acid of a

protein joined to

anoligosaccharide

(glycan)


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The biosynthesis of N-linked glycoproteins 2 stages:

› Assembly of Dol-P-P-oligosaccharide and transfer ofoligosaccharide

›

Processing of the oligosaccharide chain Is important since the most readily accessible

glycoproteins (eg. Plasma proteins) mainly belongto this group

The process itself has physiologic significance›

administration of recombinant erythropoeitin to stimulateerythropoiesis in patients with anemia› Correlation of different glycosyl transferases in various

types of cancer cells


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Produced by epithelial tissues Has a key characteristic ability to form gels,

and therefore forms functions from signalingto forming chemical barriers

Some mucins are associated with controllingmineralization,

including bone formation in

vertebrates Overexpression of mucin proteins

is associated with many types of cancer


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Mature mucins are composed of two distinct regions:

The amino- and carboxy-terminal regions are very lightlyglycosylated, but rich in cysteines. The cysteine residuesparticipate in establishing disulfide linkages within andamong mucin monomers

A large central region formed of multiple tandem repeats of

10 to 80 residue sequences in which up to half of the aminoacids are serine or threonine. This area becomes saturatedwith hundreds of O-linked oligosaccharides. N-linkedoligosaccharides are also found on mucins, but in lessabundance than O-linked sugars


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Is a generic term for the N- or O-substituted derivatives ofneuraminic acid, a monosaccharide with a nine-carbonbackbone

A constituent of both glycoproteins and gangliosides

Found widely distributed in animal tissues and to a lesser

extent in other species such as plants and bacteria Metastatic cancer cells often express a high density of

sialic acid-rich glycoproteins. This helps these late-stagecancer cells enter the blood stream. Sialic acid-richregions contribute to creating a negative charge on the

cells' surface. Since water is a polar molecule with partialpositive charges on both hydrogen atoms, it is attractedto cell surfaces and membranes. This also contributes tocellular fluid uptake.


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Carbs against Cardio: More Evidence that

Refined Carbohydrates, not Fats, Threaten theHeart› Processed carbohydrates may increase the risk of

obesity, diabetes and heart disease more than fatdoes

› a meta-analysis — which combines data from several

studies found no association between the amount ofsaturated fat consumed and the risk of heart disease.

› do not merely suggest that saturated fats are not sobad; they indicate that carbohydrates could beworse.

›

Study of 65,000 women and found that women whoate the most easily digestible and readily absorbedcarbohydrates (highest glycemic index) — were 47percent more likely to acquire type 2 diabetes thanth ith th l t l i i d

02 02. Carbohydrates

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