VL 14 (Jörg Fettke) Flashcards
Carbohydrates
Carbohydrates are present in all kingdoms of life and fulfill various functions apart from building cell walls or in energy metabolism
- Formula (CH2O)n, n => 3
- Oligosaccharides: linked monosaccharides (building blocks)
- Polysaccharides (cellulose, glycogen, starch)
Important definitions
- Glycan: term for sugars in glycoproteins/-lipids
- Glucan: only glucose
- Glycoconjugate: protein/lipid + sugar
- Glycoprotein: protein containing covalently linked sugar molecules (added as co-/post-translational modifications)
- Glycome: total complement of glycans in cell/tissue/organism
- Glycosyltransferase: E; sugar transfer from donor→acceptor→form: glycosidic link
- Glycosidase: E; hydrolyzes glycosidic linkage
- Lectin: glycan binding protein; E with sugar S, sugar-binding Ab are usually not classified as lectins; classified in different families based on CRD-sequence similarities
- Carbohydrate-recognition domain (CRD): part of glycan-binding protein (lectin) that contains sugar-binding site
- O-linked oligosaccharide/glycan: linked through O-atom, attached to Ser/Thr
- N-linked oligosaccharide/glycan: linked through N-atom (Asp)
Stereochemistry of Carbohydrates
D-Aldoses
D-Ketoses
Confirmations of hexoses
- H-atom at C1/4→destabilize boat conformation→stabilize chair conformation
- 4C1-chair conformation preferred: all OH-groups equatorial
Form of Pyranose and Furanose
Common Monosaccharide Building Blocks
Disaccherides and Polysaccherides
Disaccherides:
* Two monosaccharide
* O-glycosidic bond
* Reducing sugars: aldehyde/keto group conserved on one end (i.e. lactose, maltose)
* Non-reducing sugars: OH-group at C1 of one of both partners has condensed
→acetal (no keto/aldehyde function present in molecule (i.e. saccharose))
Monosaccherides:
* Cellulose: insoluble zick-zack layers of carbohydrates
* Starch: helic, double-helix structure
Function of glycans
Intrinsic glycan functions
* providing structural components
–> cell walls
–> ECM
* modifying protein properties
–> solubility
–> stability
Extrinsic functions resulting from glycan-lectin interactions
* directing trafficking of glycoconjugates; mediating, modulating signaling
–> Intra-/extracellular
* Mediating, modulating cell adhesion
–> Cell-cell/matrix interactions
Steps in encoding and decoding information in glycan structures
Comparison of glycans and proteins
Glycosyltransferase
- activation: nucleotide coupling
- need activated sugars
- Glycosyltransferases need
activated sugars - Activation via nucleotide
coupling - Highly specific enzymes! („One
linkage, one enzyme“)
N-linked Glycans
- generated trough pathway in ER; Asn-linked (motive: Asn-X(no Pro)-Ser(Thr), X = aa)
- differential action of glycosidases, glycosyltransferases (GTs) generates high Man, complex, hybrid typ e
- particular structures on proteins depend on GTs + their expression level
- spec. terminal elaborations added to core structures mediate spec. functions
- key objective: how GT expression, activity, regulation influences glycosylation
O-linked glycosylation:
- lack common biosynthetic pathway
- attached: Ser, Thr, Hydroxylysine
- O-GlcNAc in cytoplasm, nucleus
- O-GalNAc in mucins that hold H2O
- IgA: O-glycosylated in hinge region
- Proteoglycans: O-glycosylated proteins → strengthen ECM