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GLUCIDE = Carbohidraii

Glucidele (glicanii) au urmtoarea compoziie


de baz
I (CH2O)n or H - C - OH I Se numesc compuii polioxicarbonilici i derivaii lor. Deosebirea caracteristic este prezena a cel puin 2 grupe hidroxil (OH) i a gruprii carbonil (aldehidic COH) sau cetonic (C=O).
GLUCIDE
Grupa aldehidic aldoze

Grupa cetonic

cetoze

Clasificarea glucidelor
Dup structur Dup proprietile fizicochimice Acide (pe lng grupele hidroxil i carbonil conin grupe carboxilice) Acizii uronici i arici

Neutre (conin numai grupe hidroxil i carbonil)

Bazice (pe lng grupele hidroxil i carbonil conin grupe aminice) aminoglucide

Clasificarea dup structur


monozaharide

oligozaharide (2-10 resturi de monozah., di-, tri-,tetra zaharide

polizaharide homopolizaharide heteropolizaharide

Monozaharide Derivaii propriu-zise monozaharidelor

Trioze (C-3) Acizii Tetroze (C-4) uronici Acizii arici a. Aminozaharide Pentoze (C-5) (a.glucaric) ( glucuronic) (glucozamina) Hexoze (C-6) Glicozidele Heptoze (C-8) (nucleozide, nucleotide) Nonoze (C-9) Fosfozaharide Decoze (C-10) (glucozo6 fosfat)

Monozaharide - nomeclatura
Toate monozaharidele au terminaia oza

Aldoze(e.g., glucose) au gruparea aldehidic


H C H HO H H C C C C OH H OH OH O

Ketoze (e.g., fructose) au gruparea cetonic la C2.


CH2OH C HO H H C C C O H OH OH

CH2OH

CH2OH

D-glucose

D-fructose

Seriile izomerice D i L
D & L desemnrile se bazeaz pe configuraia n jurul atomul de C asimetric n gliceraldehid. Imaginile de jos sunt Proiectrile Fischer.
CHO H C OH HO CHO C H

CH2OH

CH2OH

D-glyceraldehyde
CHO H C OH

L-glyceraldehyde
CHO HO C H

CH2OH

CH2OH

D-glyceraldehyde

L-glyceraldehyde

Pentru monozaharidele O H cu mai multe centre C chirale, formele D sau L H C OH se refer al atomul de C HO C H asimetric cel mai departe H C OH de gruparea carbonil. H C OH

Majoritatea zaharidelor naturale sunt D izomeri.

CH2OH
D-glucose

C HO C H H C OH HO C H HO C H CH2OH
L-glucose

Seriile D & L a monozaharidelor sunt imaginile n oglind a uneia fa de alta. Au acelai nume, spre ex. D-glucoza i L-glucoza. Alte forme de stereoizomerie la monozaharide poart nume unice (se consider a fi diferite tipuri de monozaharide). Ex. glucoza, manoza, galactoza, etc.

C H C OH HO C H H C OH H C OH CH2OH
D-glucose

C HO C H H C OH HO C H HO C H CH2OH
L-glucose

Numrul de stereoizomeri este 2n, unde n este numrul de centre asimetrice.


C-6 aldozele au 4 centre asimetrice. Astfel sunt 16 stereoizomeri (8 D- i 8 Lmonozaharide).

Hemiacetal & hemiketal formation


H H O

An aldehyde can react with an alcohol to form a hemiacetal. A ketone can react with an alcohol to form a hemiketal.

C R

R'

OH

R'

C R

OH

aldehyde
R C R' O

alcohol

hemiacetal
R

"R

OH

"R

C R'

OH

ketone

alcohol

hemiketal

n soluii apoase monozaharidele se afl sub form de caten desfurat sau ciclic Pentozele i hexozele pot forma cicluri Glucoza formeaz un hemiacetal intra-molecular, la reacionarea gruprii C1 aldehidice cu C5 OH , formnd un inel hexaedric (piranozice) numit piran, sau unul pentaedric (furanozice) numit furan

CHO C C C C OH H

Reprezentarea ciclic a monozaharodelor se mai numete proiectare Haworth.


6 CH2OH

H HO H H

2 3 4 5 6

D-glucose

OH (linear form) OH

CH2OH
6 CH2OH

H
4

O H
2

H
1

H
4

O H
2

OH
1

H OH
3

H OH
3

OH

OH

OH

OH

OH

-D-glucose

-D-glucose

CH2OH O H OH OH HOH2C 6
5

2C

HO H H

C C C

O H HO
3

1 CH2OH 2

4 5 6

CH2OH

OH

OH

D-fructose (linear)

-D-fructofuranose

Fructoza formeaz sau Un inel hexaedric (piranozic), prin reacia C2 ceto grupei cu grupa OH n C6, sau Un inel pentaedric (furanozic) , prin reacia C2 ceto grupei cu grupa OH n C5.

6 CH 2OH

6 CH 2OH

H
4

O H
2

H
1

H
4

O H
2

OH
1

H OH
3

H OH
3

OH

OH

OH

OH

OH

-D-glucose

-D-glucose

Ciclizarea glucozei sau altor monozaharide contribuie la formarea unui nou centru asimetric n poziia C1. Cei doi izomeri formai se numesc anomeri, & .
Proiectarea Haworth reprezint formele izomere ale manozaharidelor ciclice avnd inele planare cu poziie diferit a grupei OH fa de C1 vanomeric: (OH mai jos de inel) (OH mai sus de inel).

H OH
4 6 5 3

H OH H O H
2

H O HO H HO H H OH OH H

HO HO H

OH 1 OH

-D-glucopyranose

-D-glucopyranose

Because of the tetrahedral nature of carbon bonds, pyranose sugars actually assume a "chair" or "boat" configuration, depending on the sugar. The representation above reflects the chair configuration of the glucopyranose ring more accurately than the Haworth projection.

Derivaii monozaharidelor
Alcoolii monozaharidelor nu au grupe aldehidice sau cetonice ; e.g., ribitol.
CH2OH H H H C C C OH OH OH

CH2OH

D-ribitol

Acizii monozaharidelor Acizii uronici sauau aldonici i alduronici


H HO H H COOH C C C C OH H OH OH H HO H H CHO C C C C OH H OH OH

Gruparea aldehiic n C1 sau OH dn C6 este oxidat pn la gruparea carboxilic formnd acizi


-acidul gluconic n cazul oxidrii grupei aldehidice - acidul glucuronic n cazul oxidrii grupei OH n poziia C-6

CH2OH

COOH

D-gluconic acid D-glucuronic acid

Acizii monozaharidelor Acizii arici se formeaz la oxidarea concomitent a gruprii aldehidice n C1 i a celei OH dn C6 pn la gruparea carboxilic

Ex. acidul glucaric

CH2OH H H OH OH H NH2 O H OH OH H H

CH2OH O H OH H O OH H N H C CH3 H

-D-glucosamine

-D-N-acetylglucosamine

Amino zaharurile - o grupare aminic substituie o grup hidroxil .


Ex. glucozamina.

Gruparea aminic paote fi acetilat formnd Nacetilglucozamina.

O H3C C NH

H O R H H OH H H OH COO HC R= HC OH OH

CH2OH

N-acetylneuraminate (sialic acid)

N-acetylneuraminate (acidul N-acetylneuraminic, denumit i acidul sialic ) este frecvent un rest terminal a catenei oligozaharide din componena glicoproteinelor . Acidul sialic confer sarcin negativ glicoproteinelor, deoarece gruparea sa carboxilic tinde s disocieze n protoni la valoarea fiziologic a pH-ului.

NUCLEOZIDE, NUCLEOTIDE

Eterii fosforici ai monozaharidelor - o grup vast de derivai , care se formeaz n cursul transformrilor glucidelor n celule.

Legturile glicozidice
Gruparea anomeric hidroxilic a unui monozaharid cu gruparea hidroxil a altui monozaharid (sau alt compus( se pot uni, eliminnd apa i formnd legturi glicozidice: R-OH + HO-R' R-O-R' + H2O E.g., metanolul reacioneaz cu guparea OH a glucozei formnd methyl glucosida (methyl-glucopyranose).
H OH H O HO HO H H H OH OH H H2O H OH H O HO HO H H OH OCH3

CH3-OH

-D-glucopyranose

methanol

methyl--D-glucopyranose

Oligozaharide
Se numesc glucidele, care conin de doi pn la 10 resturi de monozaharide. Se deosebesc dup componena monozaharidic i dup tipul legturii glicozidice.

zaharoza are legtur glicozidic ntre grupa hidroxilic anomeric a glucozei i fructozei . Deoarece configuraia C anomeric al glucozei este n poziia (O este mai jos de inel), legtura este (12). Astfel denumirea deplin a zaharozei este -D-glucopyranosyl-(12)--Dfructopyranose.)

Zaharoza, numit i sucroz este o dizaharid foarte rspndit n natur, ntlnindu-se n special n sfecla de zahr (Beta vulgaris) 12-23% i n trestia de zahr (Saccharum officinarum) 2027%, fiind cea mai comun form de zahr utilizat n alimentaie.

Maltoza, produsul hidrolizei pariale a amidonului n plante. Este un disaharid cu legtur glicozidic (1 4) ntre C1 C4 OH a dou resturi de glucoz. Este un anomer (C1 O este mai jos de inel).

6 CH2OH

6 CH2OH

H
4

O H
2 1

H
4

O H
2 1

H OH
3

H OH
3

OH

OH

OH

maltose

OH

Maltoza se gaseste in mod natural in cerealele germinate.

6 CH2OH

6 CH

2OH

H
4

O H
2 1

H O H
4

O H
2 1

OH

H OH
3

H OH
3

OH

OH

cellobiose

OH

Celobioza, un produs al scindrii celulozei, format din resturi de glucoz. Este un anomer (O n C1 se afl de asupra inelului). Legturile glicozidice (1 4) sunt repreznetate ca a zigzag, dar un rest de glucoz este n poziie inversat (rsturnat) n comparaie cu al doilea rest-

Lactoza, este un dizaharid din lapte, format din galactoz i glucoz unite prin legturi (14) glicozidice. Denumrea deplin este : -Dgalactopyranosyl(1 4)--Dglucopyranose

POLIZAHARIDELE SAU GLICANII


Se numesc glucidele macromoleculare, care conin mai mult de zece monozaharide, legate prin legturi glicozidice. Cel mai frecvent monomer este glucoza. Se ntlnesc i alte monozaharide cum ar fi: galactoza, manoza, fructoza, precum i derivaii ai monozaharidelor.

Homopolizaharide
Formate din acelai tip de monozaharide. Ex. amidonul sau celuloza formate numai din D-glucoz

Heteropolizaharide
Sunt formate din monozaharide diferite. De regul din derivai ai monozaharidelor

Homopolizaharide - homoglicani
Cel mai frecvent ntlnit homopolizaharid la plante este amidonul. Const din -amiloz i amilopectin.

-amiloz polizaharid liniar, format din molecule de D-glucoz, unite prin legturi -(1-4) glicozidice.
CH2OH H OH H OH O H OH H
1

H O

6CH OH 2 5 O 4 OH 3

CH2OH H O H O H OH H H O OH H H

CH2OH O H OH H H OH H O H

CH2OH O H OH H H OH OH H

H 1
2

OH

amylose

Amilopectina este un polimer ramificat n care catenele sunt formate din legturi (14) glicozide. Aproximativ peste fiecare 12 resturi de monozaharide n caten apar puncte de ramificare, formate din legturi (16) glicozidice. Aceast ramificare contribuie la o structur mai compact a amidonului.
CH 2OH H H OH OH H CH 2OH H OH H OH O H OH H H O H OH CH 2OH O H OH H H OH H O H 4 O H H O H H OH H CH 2OH O H OH H 1 O 6 CH 2 5 H OH 3 H CH 2OH O H 2 OH 1 O H H O H 4 OH H H O OH H H CH 2OH O H OH H H OH OH H

amylopectin

Glicogenul, este un polizaharid principal de rezerv la om i animale. Este similar dup structur cu amilopectina.

Glycogen are mai multe puncte de ramificare (16). Aceast structur extrem de ramificat permite o scindare mai rapid a glicogenului pn la glucoz, de ex. n timpul exerciiilor fizice n muchi.
CH2OH H H OH OH H CH2OH H OH H OH O H OH H H O H OH CH2OH O H OH H H OH H O H 4 O H H O H H OH H CH2OH O H OH H 1 O 6 CH2 5 H OH 3 H CH2OH O H 2 OH 1 O H H O H 4 OH H H O OH H H CH2OH O H OH H H OH H

glycogen

OH

Structura ramificat a glicogenului


n molecula glicogenului se deosebesc ramurile interne i externe, precum i catenele A, B i C. Catena C constituie pivotul i conine singurul rest de glucoz cu proprieti reductive. Cele mai ramificate sunt catenele B, iar catena A nu conine alte ramuri, se unete cu catenele B care formeaz ramurile interne.

CH2OH H OH H OH O H OH H
1

H O H

6CH OH 2 5 O 4 OH 3

CH2OH H O H H OH O H OH H H O H

CH2OH O H OH H H H OH O H

CH2OH O H OH H H H OH OH

H 1
2

OH

cellulose

Celuloza, este un polizaharid constituient al peretelui celular la plante . Este o caten liniar format din molecule de glucoz, unite prin legturi (14) glicozidice.
Datorit acestor legturi, fiecare molecul de glucoz este n poziie inversat, una fa de alta, ceea ce contribuie la formarea legturilor de H i Van der Waals, ce cauzeaz ca catenele de celuloz s fie puternice i rigide, formnd microfibrile

Schematic of arrangement of cellulose chains in a microfibril.

CH2OH H OH H OH O H OH H
1

H O H

6CH OH 2 5 O 4 OH 3

CH2OH H O H H OH O H OH H H O H

CH2OH O H OH H H H OH O H

CH2OH O H OH H H H OH OH

H 1
2

OH

cellulose

Multisubunit Cellulose Synthase complexes in the plasma membrane spin out from the cell surface microfibrils consisting of 36 parallel, interacting cellulose chains. These microfibrils are very strong. The role of cellulose is to impart strength and rigidity to plant cell walls, which can withstand high hydrostatic pressure gradients. Osmotic swelling is prevented. Explore and compare structures of amylose & cellulose using Chime.

Heteropolizaharidele acide sau mucopolizaharidele


Substane puternic hidratate, cu sarcin negativ pronunat. Se conin n substana intercelular sub form conjugat cu proteinele formn proteoglicani sau glucozaminproteoglicani

Heteropolizaharidele
n dependen de structura catenelor heteropolizaharidele se mpart n 7 tipuri principale. Acidul DAcidul hialuronic glucuronic i Nacetil DConin verigi Condroitin-4-sulfat glucozamina dizaharidice Condroitin-6-sulfat alternative Aminozaharuri Dermatansulfatul asemntore sulfatate i Heparina Heparansulfatul acidul Dglucuronic sau L-iduronic
n loc de acizi uronici conine D-galactoza

keratansulfatul

D-glucuronate
6COO

CH2OH
5

H O H
2 1 4

O H
1 O

H
4

H OH
3

OH O

NHCOCH3

OH

N-acetyl-D-glucosamine

hyaluronate

Glycosaminoglycans (mucopolysaccharides) are linear polymers of repeating disaccharides.


The constituent monosaccharides tend to be modified, with acidic groups, amino groups, sulfated hydroxyl and amino groups, etc. Glycosaminoglycans tend to be negatively charged, because of the prevalence of acidic groups.

Acidul hialuronic este polizaharid nesulfatat cu strucut liniar. Este format din acidul D-glucuronic i Nacetilglozamina. Legturile glicozidice sunt de tipul (13) & (14).
D-glucuronate
6COO

CH2OH
5

H O H
2 1 4

O H
1 O

H
4

H OH
3

OH O

NHCOCH3

OH

N-acetyl-D-glucosamine

hyaluronate

Condroitinsulfaii
Cele mai rspndite heteropolizaharide acide. Se disting:
Denumirea Locul sulfatrii carbon 4 of the Nacetylgalactosamine (GalNAc) sugar Denumirea sistematic

Chondroitin sulfate A

chondroitin-4-sulfate

Condroitin suflate B
Chondroitin sulfate C

Dermatan sulfatul
carbon 6 of the GalNAc sugar chondroitin-6-sulfate
carbon 2 of the glucuronic acid and 6 of the GalNAc sugar carbons 4 and 6 of the GalNAc sugar

Chondroitin sulfate D

chondroitin-2,6-sulfate

Chondroitin sulfate E

chondroitin-4,6-sulfate

Condroitinsulfaii
Chondroitin-4-sulfate: R = H; R = SO H; R = 1 2 3 3 H. Chondroitin-6-sulfate: R = SO H; R , R = H.

Se conin n piele, oase cartilaje, trahee, aort, arterii. n celule se gsesc n complex cu proteina ca parte a proteinglicanilor. Heparina i Heparan Dermatansulfatul se conine n aort i spre sulfatul nu intr n deosebire de ali condroitinsulfai posed propriti componena substanei antcoagulante intercelulare. Sunt produse de matocitele Keratansulfatul se conine n cornee, legat esutului conjuctiv. covalent cu proteina i asigur transparena Complexul heparinoptic a acesteia glucoproteid manifest proprieti anticoagulante.

core protein

heparan sulfate glycosaminoglycan transmembrane -helix cytosol

Proteoglycans are glycosaminoglycans that are


covalently linked to serine residues of specific core proteins. The glycosaminoglycan chain is synthesized by sequential addition of sugar residues to the core protein.

Some proteoglycans of the extracellular matrix bind non-covalently to hyaluronate via protein domains called link modules. E.g.: Multiple copies of the aggrecan proteoglycan associate with hyaluronate in cartilage to form large complexes. Versican, another proteoglycan, binds hyaluronate in the extracellular matrix of loose connective tissues.
D-glucuronate
6

CH2OH
5

Websites on: Aggrecan Aggrecan & versican.


H
4

6COO

H O H
2 1 4

O H
1 O

H OH
3

OH O

NHCOCH3

OH

N-acetyl-D-glucosamine

hyaluronate

iduronate-2-sulfate
H H COO OH O H H H OSO3

N-sulfo-glucosamine-6-sulfate
CH2OSO3 H O H OH O H O H NHSO3 H

heparin or heparan sulfate - examples of residues

Heparan sulfate is initially synthesized on a membraneembedded core protein as a polymer of alternating N-acetylglucosamine and glucuronate residues. Later, in segments of the polymer, glucuronate residues may be converted to the sulfated sugar iduronic acid, while N-acetylglucosamine residues may be deacetylated and/or sulfated.

PDB 1RID

Heparin, a soluble glycosaminoglycan found in granules of mast cells, has a structure similar to that of heparan sulfates, but is more highly sulfated. When released into the blood, it inhibits clot formation by interacting with the protein antithrombin. Heparin has an extended helical conformation.
heparin: (IDS-SGN)5
C O N S

Charge repulsion by the many negatively charged groups may contribute to this conformation.
Heparin shown has 10 residues, alternating IDS (iduronate2-sulfate) & SGN (N-sulfo-glucosamine-6-sulfate).

Some cell surface heparan sulfate glycosaminoglycans remain covalently linked to core proteins embedded in the plasma membrane.

core protein

heparan sulfate glycosaminoglycan transmembrane -helix cytosol

The core protein of a syndecan heparan sulfate proteoglycan includes a single transmembrane -helix, as in the simplified diagram above. The core protein of a glypican heparan sulfate proteoglycan is attached to the outer surface of the plasma membrane via covalent linkage to a modified phosphatidylinositol lipid.

Proteins involved in signaling & adhesion at the cell surface recognize & bind heparan sulfate chains.

E.g., binding of some growth factors (small proteins) to cell surface receptors is enhanced by their binding also to heparan sulfates. Regulated cell surface Sulf enzymes may remove sulfate groups at particular locations on heparan sulfate chains to alter affinity N-sulfo-glucosamine-6-sulfate iduronate-2-sulfate for signal CH2OSO3 H proteins, e.g., O H H growth factors. H COO O H
Diagram
by Kirkpatrick & Selleck.
OH H H H OSO3 H NHSO3 O OH H O

heparin or heparan sulfate - examples of residues

CH2OH

C O O CH2 CH NH O H

Oligosaccharides that are covalently attached to proteins or to membrane lipids may be linear or branched chains.

H H OH OH H

serine residue

HN

CH3

-D-N-acetylglucosamine

O-linked oligosaccharide chains of glycoproteins vary in complexity. They link to a protein via a glycosidic bond between a sugar residue & a serine or threonine OH. O-linked oligosaccharides have roles in recognition, interaction, and enzyme regulation.

CH2OH H H OH OH H HN O H O H C CH3 O CH2

C CH NH

serine residue

-D-N-acetylglucosamine

N-acetylglucosamine (GlcNAc) is a common O-linked glycosylation of protein serine or threonine residues. Many cellular proteins, including enzymes & transcription factors, are regulated by reversible GlcNAc attachment.

Often attachment of GlcNAc to a protein OH alternates with phosphorylation, with these 2 modifications having opposite regulatory effects (stimulation or inhibition).

CH2OH H H OH OH H HN C O O H H HN

O C CH2

HN CH C HN HC C HN HC C R O R O O

Asn

CH3

N-acetylglucosamine

Initial sugar in N-linked glycoprotein oligosaccharide

Ser or Thr

N-linked oligosaccharides of glycoproteins tend to be complex and branched. First N-acetylglucosamine is linked to a protein via the side-chain N of an asparagine residue in a particular 3-amino acid sequence.

NAN Gal NAG Man

NAN Gal NAG

NAN Gal NAG

Man

N-linked oligosaccharide Key:


NAN = N-acetylneuraminate Gal = galactose NAG = N-acetylglucosamine Man = mannose Fuc = fucose

Man NAG NAG Fuc

Asn

Additional monosaccharides are added, and the N-linked oligosaccharide chain is modified by removal and addition of residues, to yield a characteristic branched structure.

Many proteins secreted by cells have attached N-linked oligosaccharide chains.


Genetic diseases have been attributed to deficiency of particular enzymes involved in synthesizing or modifying oligosaccharide chains of these glycoproteins. Such diseases, and gene knockout studies in mice, have been used to define pathways of modification of oligosaccharide chains of glycoproteins and glycolipids. Carbohydrate chains of plasma membrane glycoproteins and glycolipids usually face the outside of the cell. They have roles in cell-cell interaction and signaling, and in forming a protective layer on the surface of some cells.

Lectins are glycoproteins that recognize and bind to specific oligosaccharides. Concanavalin A & wheat germ agglutinin are plant lectins that have been useful research tools. The C-type lectin-like domain is a Ca++-binding carbohydrate recognition domain in many animal lectins.

Recognition/binding of CHO moieties of glycoproteins, glycolipids & proteoglycans by animal lectins is a factor in: cell-cell recognition adhesion of cells to the extracellular matrix interaction of cells with chemokines and growth factors recognition of disease-causing microorganisms initiation and control of inflammation.

Examples of animal lectins: Mannan-binding lectin (MBL) is a glycoprotein found in blood plasma.

It binds cell surface carbohydrates of disease-causing microorganisms & promotes phagocytosis of these organisms as part of the immune response.

Selectins are integral proteins of mammalian cell plasma membranes with roles in cell-cell recognition & binding. outside The C-type lectin-like domain is at the end of a multi-domain cytosol extracellular segment extending out from the cell surface.

selectin

lectin domain

transmembrane -helix cytoskeleton binding domain

A cleavage site just outside the transmembrane -helix provides a mechanism for regulated release of some lectins from the cell surface. A cytosolic domain participates in regulated interaction with the actin cytoskeleton.