DLA Before Lecture 27 Flashcards
N-glycosylation of proteins
Protein synthesis begins and the polypeptide chain is extruded into the rER
A mamnose-rich oligosacharide is synthesized on lipid dolichol-PP=pyrophosphate, dolichol has many isoprene units which anchor it in the rER membrane
The oligosacharide is transferred from dolichol to amide N of an asparagine of polypeptide
Trimming of the carbo chain begins as he protein moves thru rER
In Golgi, further trimming and/or addition of monosaccharides, form complex glycoproteins and high-mannose glycoproteins
N-glycosylated glycoproteins are transported into lysosomes, secreted into the blood, or incorporated into the PM
I-cell disease
Caused by a deficiency to phosphorylate mannose
Characterized by skeletal abnormalities, restricted joint movement, coarse facial features, and severe phychomotor impairment
Death usually occurs by 8yo
Different molecules are not degraded and accumulate forming inclusion bodies
Diagnosis: detection of inclusions in lymphocytes or cultured skin fibroblasts, released lysosomal enzyme into blood
Mucolipidosis type II
Lysosomal enzymes
N-linked glycoroteins the receive in the cid-Golgi a mannose 6-P marker > formed by a specific phosphotransferase which recognizes all potential lysosomal enzymes
Mannose 6-P receptors
In the trans-Golgi bind the marked enzymes and package them into vesicles for transport into lysosomes
Recycled and enzyme is active inside lysosomes after cleavage of the phosphate of the M6P marker
Proteoglycan
Contain mainly GAGs (up to 95%) and a small amount of protein
O-glycosylation of the core protein
Part of ECM
Glycoprotein
Mainly protein and a small amount of sugar which are often branched
O- and N-glycosylation
Residues for O-linked glycosylation
Serine of threonine
Hydroxy-lysine in collagen
Steps for O-glycosylation of proteins
Protein is synthesized on the rER and extrudes into its lumen
The first sugar is enzymatically transferred and linked directly to OH or ser and thr or hydroxylysine
Sugars in O-linkage are added individually directly to the protein mainly in the Golgi by glycosyl transferase bound to the Golgi membrane
Enzyme recognize actual structure and add individually the appropriate sugar
used in synthesis of proteoglycans, glycocalyx, blood group, and mucins
Blood types
O-linked glycoproteins
H substance = Fuc-Gal-GlcNAc-R (R is protein or ceramide = lipid)
Type O: no sugar linked to Gal of H substance
Type A: GalNAc linked to Gal
Type B: galactose linked to Gal
Type AB: mixture of type A and B
Mucins
Special glycoproteins that contain 50% carbohydrates
Protein is rich in ser and thr for O-linkage
Salivary mucins
1 N-acetylglucosamine linked to ser or thr
This sugar binds to sialic acid (NANA) > mucins with many negative charges
Mucus
Mucins and water, protect and lubricates many internal body surfaces
Glycocalyx of endothelial cells components and functions
Glycoproteins and glycolipids
Cell-cell recognition
Sieving barrier
Inhibition of platelet adherence
Prevention of leukocyte adhesion
Unwanted binding and adherence by viruses and bac
Viruses that infect animal cells (influnza virus) bind to glycoproteins on the cell surface as the first step of infection
Bac adhere and colonize or infect
Bac toxin bind to a surface glycolipid before entering cell
E. coli attaches to
Mannose residue on PM of human cheek cells
Helicobacter pyloci attaches to
The gastric surface
This bac leads to ulcers by interact with a specific blood gp antigen of the gastric epothelium
Structure of glycosaminoglycans = GAGs
Long, branched chains of negatively charged sugars, often sulfated
Repeating disaccharide units:
Position 1: acidic sugar > glucouronic acid or iduronic acid
Position 2: amino sugar > glucosamine of galactosamine, can be acetylated
Resilience of GAGs
Strong negative charges from the carboxyl and sulfate gps
Bind large amounts of water producing a gel-link matrix, part of ECM
React to compression with squeezing water out and to relaxation with absorbing water
Functions of GAGs
Flexible support of ECM
Molecular sieve
Lubricants
Shock-absorber
Chondroitin sulfates
Most abundant GAGs in the body
Sulfated in position 4 or 6
Found in: Cartilage Bone Ligaments Aorta
Glucuronic acid > beta 1-3 > N-acetyl galactosamine
Keratan sulfates = KS
Contain sulfated galactose in position 1
Most heterogenous regarding their sugar
Found in:
Cartilage
Cornea, where need transparence
Gla > beta 1-4 > GlcNAC
Dermatan sulfates
Found in:
Skin
Blood vessel
Heart valve
IdUA > beta 1-3 > GalNAC
Heparan sulfate
Found in:
BM
Cell surface for recognition
Sulfated glucuronic acid or iduronic acid
GlcUA > alpha 1-4 > GlcN
Heparin
Anticoagulant: facilitate inhibition of thrombin
Contain many iduronyl sulfates
GAG with the largest amount of sulfates and negative charges
Not in ECM, in mast cells that line arteries of lung, liver, and spleen
Released from intracellular granules
Hyaluronic acid is a special GAG that is
Not sulfated
Not colavently attached to a protein
Synthesized step by step directly into the extracellular space
Provides extracellularly the central strand in proteoglycan aggregates
Connected to core protein via link proteins
Locations and functions of hyaluronic acid
Found in: Vitreous humor of the eye Synovial fluid of the joints Cartilage Loose connective tissues
Facilitates cell migration in:
Embryogenesis (neural tube closure)
Morphogenesis
Wound repair
Proteoglycan aggregates
Assembled in ECM using hyaluronic acid and proteoglycans
Proteoglycans are formed intracellularly by O-glycosylation of the core protein and are then released into the ECM
Shock absorber and lubricant
GAG linkage region
Core protein-serine side chain-trihexoside linker region-GAGs
