KARBOHIDRAT * Reaksi monosakarida

* Ikatan glikosida * Fungsi karbohidrat

Dra. Nies Suci Mulyani,MS

Monosakarida
Memiliki atom karbon 3 sampai 7 Setiap atom karbon memiliki gugus hidroksil, keton atau aldehida. Setiap molekul monosakarida memiliki 1 gugus keton atau 1 gugus aldehida
Gugus aldehida selalu berada di atom C pertama Gugus keton selalu berada di atom C kedua

Monosakarida
Ketosas (mis: fruktosa) biasanya Aldosa (mis: glukosa) memiliki gugus aldehida pada salah satu memiliki gugus keto pada atom C2. ujungnya.
H C H HO H H C C C C OH H OH OH O

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

CH2OH

CH2OH

D-glucose

D-fructose

Notasi D vs L
CH O Notasi D & L dilakukan karena adanya atom C H C OH dengan konfigurasi CH2OH asimetris seperti pada D-g li s eraldehi da gliseraldehida. CH O CH O HO C H

CH2OH

L-glis era ldehi da

CH O

Penampilan dalam bentuk gambar bagian bawah disebut Proyeksi Fischer.

OH

HO

CH2OH

CH2OH

D-glyceraldehyde

L-glis eraldehida

Penamaan Gula
Untuk gula dengan atom C asimetrik lebih dari 1, notasi D atau L ditentukan oleh atom C asimetrik terjauh dari gugus aldehida atau keto.
O H O H

Gula yang ditemui di alam adalah dalam bentuk isomer D.

C H C OH HO C H H C OH H C OH CH2OH
D-glukosa

C HO C H H C OH HO C H HO C H CH2OH
L-glukosa

Gula dalam bentuk D merupakan bayangan cermin dari gula dalam bentuk L. Kedua gula tersebut memiliki nama yang sama, misalnya Dglukosa & L-glukosa.

C H C OH HO C H H C OH H C OH CH2OH
D-glukosa

C HO C H H C OH HO C H HO C H CH2OH
L-glukosa

Stereoisomers lainnya memiliki names yang unik, misalnya glukosa, manosa, galaktosa, dll. Jumlah stereoisomer adalah 2n, dengan n adalah jumlah pusat asimetrik. Aldosa dengan 6-C memiliki 4 pusat asimetrik, oleh karenanya memiliki 16 stereoisomer (8 gula berbentuk D dan 8 gula berbentuk L).

Pembentukan hemiasetal & hemiketal

Aldehida dapat bereaksi dengan alkohol membentuk hemiasetal.
Keton dapat bereaksi dengan alkohol membentuk hemiketal.
H C R O H

R'

OH

R'

C R

OH

aldehida
R C O

alkohol

hemiasetal
R

"R

OH

"R

OH

R'

R'

keton

alkohol

hemiketal

Pentosa dan heksosa dapat membentuk struktur siklik melalui reaksi gugus keton atau aldehida dengan gugus OH dari atom C asimetrik terjauh. Glukosa membentuk hemiasetal intramolekular sebagai hasil reaksi aldehida dari C1 & OH dari atom C5, dinamakan cincin piranosa.

C HO C OH

2 3 4 5

HO
H

C
C

H
OH

D-glukosa

(bentuk linier)

OH

6
6 CH2OH

C H 2O H
6 CH2OH

H
4

O H
2

H
1

H
4

OH
1

H OH
3

H OH
3

H
2

OH

OH

OH

OH

OH

a-D-glukosa

b-D-glukosa

Penampilan dalam bentuk gula siklik disebut proyeksi Haworth.

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-fruktosa (linear)

a-D-fruktofuranosa

Fruktosa dapat membentuk Cincin piranosa, melalui reaksi antara gugus keto atom C2 dengan OH dari C6. Cincin furanosa, melalui reaksi antara gugus keto atom C2 dengan OH dari C5.

6C H 2OH

6 C H OH
2

H
4

H
1

H
4

O H
2

OH
1

H OH
3

H
2

H OH
3

OH

OH

OH

OH

OH

a-D-glukosa

b -D-glukosa

Pembentukan cincin siklik glukosa menghasilkan pusat asimetrik baru pada atom C1. Kedua stereoisomer disebut anomer, a & b. Proyeksi Haworth menunjukkan bentuk cincin dari gula dengan perbedaan pada posisi OH di C1 anomerik : a (OH di bawah struktur cincin) b (OH di atas struktur cincin).

H OH
4 6

H OH H O
5

H O

HO HO
3

HO H HO OH 1
OH H

OH

OH
H

a-D-glukopiranosa

b-D-glukopiranosa

Karena sifat ikatan karbon yang berbentuk tetrahedral, gula piranosa membentuk konfigurasi kursi" atau perahu", tergantung dari gulanya. Penggambaran konfigurasi kursi dari glukopiranosa di atas lebih tepat dibandingkan dengan proyeksi Haworth.

Turunan gula
CO O H

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

CH2OH H H H C C C OH OH OH

H HO H H

C C C C

OH H OH OH

CH2OH

CH2OH

CO O H

D-ribitol

Asam D-glukonat

Asam D-glukuronat

Gula alkohol tidak memiliki gugus aldehida atau ketone; misalnya ribitol.
Gula asam gugus aldehida pada atom C1, atau OH pada atom C6, dioksidasi membentuk asam karboksilat; misalnya asam glukonat, asam glukuronat.

Oksidasi gula aldehida

H O

C H
HO

CO O H

C
C

OH
H

C C C C

OH H OH OH

Oksidator

HO H H

H H

C C

OH OH

CH2OH

CH2 O H

D-glucose

Asam D-glukonat

Oksidasi gula aldehida

Gula yang dapat dioksidasi adalah senyawa pereduksi. Gula yang demikian disebut sebagai gula pereduksi. Senyawa yang sering digunakan sebagai pengoksidasi adalah ion Cu+2, yang berwarna biru cerah, yang akan tereduksi menjadi ion Cu+, yang berwarna merah kusam. Hal ini menjadi dasar bagi pengujian Benedict yang digunakan untuk menentukan keberadaan glukosa dalam urin, suatu pengujian bagi diagnosa diabetes.

Oksidasi gula aldehida

Glukosa + Cu++
panas & alk . pH

Gluconic acid + Cu2O (Cu2O is insol ppt)

glukosa oksidase

Glukosa + O2
Asam glukonat + H2O2 (H2O2 nya diukur)

Glukosa + ATP

heksokinase

Glukosa-6-P + ADP (G-6-Pnya diukur)

Turunan gula
C H2OH
H H OH OH H NH 2 O H OH OH H N H H H H OH CH 2OH O H O OH C CH 3 H

a-D-glukosamina

a-D-N-asetilglukosamina

Gula amino - gugus amino menggantikan gugus hidroksil. Sebagai contoh glukosamina.
Gugus amino dapat mengalami asetilasi, seperti pada N-asetilglukosamina.

Ikatan Glikosida
Gugus hidroksil anomerik dan gugus hidroksil gula atau senyawa yang lain dapat membentuk ikatan yang disebut ikatan glikosida dengan membebaskan air : R-OH + HO-R' R-O-R' + H2O Misalnya methanol bereaksi dengan gugus OH anomerik dari glukosa membentuk metil glukosida (metil-glukopiranosa).
H OH
H O H2O H OH H OH H O HO HO H H H OH OCH3

HO HO H

CH3- O H

OH

a-D-glukopiranosa

metanol

Metil-a-D-glukopiranosa

Disaccharides:
Maltose, a cleavage product of starch (e.g., amylose), is a disaccharide with an a(1 4) glycosidic link between C1 - C4 OH of 2 glucoses. It is the a anomer (C1 O points down).

6 CH2OH

6 CH2OH

H
4

O H
2 1

H
4

O H
2 1

H OH
3

H OH
3

OH

OH

H
6 CH 2OH

OH

maltose

OH

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

Cellobiose, a product of cellulose breakdown, is the otherwise equivalent b anomer (O on C1 points up). The b(1 4) glycosidic linkage is represented as a zig-zag, but one glucose is actually flipped over

Other disaccharides include:

Sucrose, common table sugar, has a glycosidic bond linking the anomeric hydroxyls of glucose & fructose. Because the configuration at the anomeric C of glucose is a (O points down from ring), the linkage is a(12). The full name of sucrose is a-D-glucopyranosyl(12)-b-D-fructopyranose.)

Lactose, milk sugar, is composed of galactose & glucose, with b(14) linkage from the anomeric OH of galactose. Its full name is b-D-

Polysaccharides
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

Plants store glucose as amylose or amylopectin, glucose polymers collectively called starch. Glucose storage in polymeric form minimizes osmotic effects.
Amylose is a glucose polymer with a(14) linkages. It adopts a helical conformation. The end of the polysaccharide with an anomeric C1 not involved in a glycosidic bond is called the reducing end.

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 O H H O H

CH 2OH O H OH H 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

amylopectin

CH 2OH H O OH H O H OH H H OH OH H

H O

H 4

OH

Amylopectin is a glucose polymer with mainly a(14) linkages, but it also has branches formed by a(16) linkages. Branches are generally longer than shown above. The branches produce a compact structure & provide multiple chain ends at which enzymatic cleavage can occur.

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 O H H O H

CH2OH O H OH H 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

glycogen

CH2OH O H OH H H OH OH H

H O

H 4

OH

Glycogen, the glucose storage polymer in animals, is similar in structure to amylopectin. But glycogen has more a(16) branches. The highly branched structure permits rapid release of glucose from glycogen stores, e.g., in muscle during exercise. The ability to rapidly mobilize glucose is more essential to animals than to plants.

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

Cellulose, a major constituent of plant cell walls, consists of long linear chains of glucose with b(14) linkages. Every other glucose is flipped over, due to the b linkages. This promotes intra-chain and inter-chain H-bonds and
van der Waals interactions, that cause cellulose chains to be straight & rigid, and pack with a crystalline arrangement in thick bundles called microfibrils.

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.

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 polymers of repeating disaccharides. Within the disaccharides, the sugars 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.

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

Hyaluronate is a glycosaminoglycan with a repeating disaccharide consisting of 2 glucose derivatives, glucuronate (glucuronic acid) & N-acetylglucosamine. The glycosidic linkages are b(13) & b(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

Proteoglycans are glycosaminoglycans that are

covalently linked to specific core proteins. Some proteoglycans of the extracellular matrix in turn link non-covalently to hyaluronate via protein domains called link modules.

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
For example, in cartilage multiple copies of the aggrecan proteoglycan bind to an extended hyaluronate backbone to form a large complex. Versican, another proteoglycan that binds to hyaluronate, is in the extracellular matrix of loose connective tissues. See web sites on aggrecan and aggrecan plus versican.

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 membrane-embedded 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 Nacetylglucosamine 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 (iduronate-2sulfate) & SGN (N-sulfo-glucosamine-6-sulfate).

core protein

heparan sulfate glycosaminoglycan transmembrane a-helix cytosol

Some cell surface heparan sulfate glycosaminoglycans remain covalently linked to core proteins embedded in the plasma membrane. Proteins involved in signaling & adhesion at the cell surface recognize and bind segments of heparan sulfate chains having particular patterns of sulfation.

CH2OH

CH2 CH O O Oligosaccharides H H NH serine that are covalently H OH residue attached to OH O H proteins or to H HN C CH3 membrane lipids b-D-N-acetylglucosamine may be linear or branched chains. 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

b-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 Nlinked oligosaccharide chain is modified by removal and addition of residues, to yield a characteristic branched structure.

Many proteins secreted by cells have attached Nlinked 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. A few examples:

Concanavalin A and wheat germ agglutinin are plant lectins that have been useful research tools. Mannan-binding lectin (MBL) is a glycoprotein found in blood plasma. It associates with cell surface carbohydrates of disease-causing microorganisms, promoting 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.
A lectin-like domain is at the end of an extracellular segment that extends out from the cell surface.

selectin

lectin domain

outside transmembrane a-helix cytoskeleton binding domain

cytosol

A cleavage site just outside the transmembrane ahelix provides a mechanism for regulated release of some lectins from the cell surface.

A cytosolic domain participates in regulated interaction with the actin cytoskeleton.