Download What sort of Science is Glycoscience?

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
Glycosciences: Glycobiology & Glycochemistry
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.
Glycosciences: Glycobiology & Glycochemistry
DNA
RNA
PROTEINS
ENZYMES
REGULATORY
FACTORS
GLYCANS
SIGNALLING
MOLECULES
LIPIDS
GLYCOLIPIDS
MICROBES
PARASITES
PHYSICAL
ENVIRONMENT
CELL
GLYCOPROTEINS
PROTEOGLYCANS
MATRIX
TISSUES & ORGANS
DNA
ORGANISM
DNA
DIET
Glycans cover the surface of all eukaryotic cells, all
prokaryotic cells and many viruses
Glycan: A generic term for any sugar or assembly of sugars, in free form or
attached to another molecule = +/- saccharide or carbohydrate
GLYCANS CAN CONSTITUTE A MAJOR PORTION OF THE MASS OF
A GLYCOCONJUGATE
glycosylphosphatidylinositol
Schematic representation of the
Thy-1 glycoprotein
Glycoconjugate: A molecule in which one or more glycan units are covalently linked to
a noncarbohydrate entity
Glycosciences: Glycobiology & Glycochemistry
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.
Glycosciences: Glycobiology & Glycochemistry
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
Basic glycobiology concepts
Common monosaccharides found in vertebrates
Basic glycobiology concepts
Symbol nomenclature for structural depictions
Monosaccharide symbol set
c
b
STANDARD SYMBOLS FOR GLYCAN STRUCTURES
N-Linked
α6
β4
β2
O-Linked
α6
β4
β4
α3
α6
β4
α3
α6
β4
α3
β2
β6
β3
Fucα
α1
NeuAcα
α2-6Galβ
β1-4GlcNAc β1-2Manα
α1
NeuAc α 2-3Gal β 1-4GlcNAc β 1
6
6
Manβ
β1-4GlcNAc β1-4GlcNac- Asn
3
6
GalNAc α -Thr
3
NeuAcα
α2-6Galβ
β1-4GlcNAc β1-2Manα
α1
NeuAc α 2-3Gal β 1
Key:
NeuAc
Gal
Glc
Man
Fuc
GalNAc
GlcNAc
General pathways for biosynthesis
Common classes of animal glycans
phosphoethanolamine
phosphatidylinositol
General pathways for biosynthesis
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
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, SialylTN is an ideal candidate for boosting the patient’s immune system specifically against a unique tumorassociated 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 Nacetyllactosamines, on O-GalNAc glycans (type-3), or on glycolipids (type-4).
Glycosciences:
Biosynthesis
Glycobiology
and heterogeneity
& Glycochemistry
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
Generalized Glycosyltransferase
Reaction
Nucleotide-Sugar + HO-Acceptor
Glycosyltransferase
Nucleotide
Sugar-O-Acceptor
(Product)
Glycosciences:
Biosynthesis
Glycobiology
and heterogeneity
& Glycochemistry
Most glycosylation reactions use activated sugar donors
Biosynthesis and heterogeneity
Biosynthesis and interconversion of monosaccharides
Biosynthesis and e-learning
heterogeneity
Glycosciences: Glycobiology & Glycochemistry
course
Glycosylation Reactions
Biosynthesis and heterogeneity
Glycosyltransferases
Glycosyltransferase Donor
# Genes
Family
Substrates (min)
FucosylSialylGalactosylN-AcetylglucosaminylN-AcetylgalactosaminylMannosylGlucosyl-
GDP-Fucose
CMP-NeuAc
UDP-Gal
UDP-GlcNAc
UDP-GalNAc
GDP-Man
UDP-Glc
11
20
19
34
30
13
8
The Big Picture
Biosynthesis
Transferases &
Hydrolases
잠;
Glycan
Glycan-Binding Proteins
(Lectins)
Function
Thank you!
잠;