What sort of Science is Glycoscience? (Introductory lecture) · Paula Videira Faculdade de...

Glycosciences: Glycobiology & Glycochemistry e-learning course

What sort of Science is

Glycoscience?

(Introductory lecture)

Paula Videira

Faculdade de Ciências Médicas

Nova University, Lisbon Portugal

Glycosciences: Glycobiology & Glycochemistry

Glycoscience is the study of structure and

function of carbohydrates — biological

sugars

Glycobiology and Glycochemistry are two

main subareas


More complex deffinition for

Glycosciences

• The study of the structure, biosynthesis,

biology, and evolution of saccharides (sugar

chains or glycans) that are widely distributed

in nature, and the proteins that recognize

them.

• The branch of science concerned with the

role of sugars in biological systems.


DNA RNA PROTEINS

PHYSICAL ENVIRONMENT

ENZYMES

MICROBESPARASITES

GLYCOPROTEINSPROTEOGLYCANS

GLYCOLIPIDS

GLYCANS

ORGANISM

MATRIXCELL

TISSUES & ORGANS

DNA

SIGNALLINGMOLECULES

REGULATORYFACTORS DIET

LIPIDS

DNA

Glycan: A generic term for any sugar or assembly of sugars, in free form or

attached to another molecule = +/- saccharide or carbohydrate

Glycans cover the surface of all eukaryotic cells, all

prokaryotic cells and many viruses

Schematic representation of the

Thy-1 glycoprotein

glycosylphosphatidylinositol

GLYCANS CAN CONSTITUTE A MAJOR PORTION OF THE MASS OF

A GLYCOCONJUGATE

Glycoconjugate: A molecule in which one or more glycan units are covalently linked to

a noncarbohydrate entity


SURFACE GLYCOSYLATION IS UNIVERSAL IN LIVING ORGANISMS

• Every free-living cell and every cell within multi-cellular organisms are

covered with dense & complex layer of glycans.

• Even enveloped viruses that bud from surfaces of infected cells carry

with them the glycosylation patterns of the host cell.

• Most secreted molecules are glycosylated, and extracellular matrices of

multicellular organisms are rich in glycans

• Biofilms/ matrices secreted by unicellular organisms also contain

glycans.

• Reasons for apparent universality of cell-surface and secreted

glycosylation not clear.

• Apparently, evolution selected for glycans as being the most diverse

and flexible molecules for the interface between cells and the

extracellular milieu.


Basic concepts

• Glycan: generic term for any sugar or assembly of sugars (free form or attached to another molecule). May be used interchangeably with saccharide or carbohydrate.

• Glycoconjugate: A molecule in which one or more glycan units are covalently linked to a noncarbohydrate entity (protein or lipid).

• Carbohydrate: more generic term which includes monosaccharides, oligosaccharides, and polysaccharides as well as derivatives of these compounds

Common monosaccharides found in vertebrates

Basic glycobiology concepts

Monosaccharide symbol set b

c

Symbol nomenclature for structural depictions

Basic glycobiology concepts

Key:Gal GlcNAcFucNeuAc GalNAcGlc Man

N-Linked O-Linked

NeuAcαααα2-6Galββββ1-4GlcNAcββββ1-2Manαααα1

NeuAcαααα2-6Galββββ1-4GlcNAcββββ1-2Manαααα1

Manββββ1-4GlcNAcββββ1-4GlcNac-Asn6

3

6

Fucαααα1NeuAc αααα2-3Gal ββββ1-4GlcNAc ββββ1

NeuAc αααα2-3Gal ββββ1

GalNAc αααα-Thr6

3

αααα3

αααα6ββββ4β4β4β4β4

αααα6αααα6 ββββ4 ββββ2

αααα6 ββββ4 ββββ2

αααα3

αααα3

β4β4β4β4 β6β6β6β6

ββββ3

STANDARD SYMBOLS FOR GLYCAN STRUCTURES

Common classes of animal glycansGeneral pathways for biosynthesis

phosphatidylinositol

phosphoethanolamine

Initiation and maturation of the major types of eukaryotic

glycoconjugates in relation to subcellular trafficking in the ER-Golgi–

plasma membrane pathway

General pathways for biosynthesis

General pathways for biosynthesis

Vaccination with Theratope® (STn-KLH) as treatment for breast cancer

Leona A Holmberg, Brenda M Sandmaier

< Sialyl-Tn is a carbohydrate associated with MUC1. It is a unique tumor-associated antigen, present on

many adenocarcinomas including breast, ovarian, colorectal, gastric and pancreatic. Consequently, Sialyl-

TN is an ideal candidate for boosting the patient’s immune system specifically against a unique tumor-

associated antigen. The cancer vaccine Theratope® was developed by Biomira, Inc. using a synthetic

Sialyl-Tn antigen that emulates the unique carbohydrate on human cancer. Clinical trials have

predominately been carried out in breast cancer patients and these trials are outlined in this profile.

The A, B, and H blood group antigens are glycans presented on the type-1 or type-2 N-

acetyllactosamines, on O-GalNAc glycans (type-3), or on glycolipids (type-4).


GENERAL PRINCIPLES

how do we get the sugars?

• Glucose and fructose are major carbon and energy

sources for most organisms as yeast and humans.

• Most organisms can derive monosaccharides needed

for glycan biosynthesis from these sources.

• Not all of these biosynthetic pathways are equally

active in all types of cells.

Biosynthesis and heterogeneity

Nucleotide-Sugar + HO-Acceptor

Sugar-O-Acceptor(Product)

Nucleotide

Glycosyltransferase

Generalized Glycosyltransferase

Reaction



Most glycosylation reactions use activated sugar donors


Biosynthesis and interconversion of monosaccharides


Glycosciences: Glycobiology & Glycochemistry e-learning course

Glycosylation Reactions


Glycosyltransferases

GlycosyltransferaseFamily

DonorSubstrates

# Genes(min)

Fucosyl- GDP-Fucose 11

Sialyl- CMP-NeuAc 20

Galactosyl- UDP-Gal 19

N-Acetylglucosaminyl- UDP-GlcNAc 34

N-Acetylgalactosaminyl- UDP-GalNAc 30

Mannosyl- GDP-Man 13

Glucosyl- UDP-Glc 8


잠;

The Big PictureBiosynthesis

Glycan

Function

Transferases &

Hydrolases

Glycan-Binding Proteins

(Lectins)

잠;

Thank you!

What sort of Science is Glycoscience? (Introductory lecture) · Paula Videira Faculdade de...

Documents

Transcript of What sort of Science is Glycoscience? (Introductory lecture) · Paula Videira Faculdade de...