Lecture 27 + DLA 21 Flashcards
What amino acid is able to be N-glycosylated?
Asparagine in the rER
How does N-glycosylation occur?
- protein synthesis occurs and the peptide chain is taken to the rER
- A branched oligosaccharide is synthesized on dolichol pyrophsphate
- The oligosaccharide is transferred from the dolichol to the amide N of the aparagine
- Trimming of the carbo chain occurs while it is moving through the rER
- Goes to golgi were more trimming and additions occur (monosaccharides)
What are the different fates of N-glycosylated proteins?
can be transported to lysosomes, secreted into the blood, or placed in the cell membrane
How are N-glycoslyated proteins moved from the golgi to the lysosome?
- It needs to have a mannose 6-P marker that is formed by a phosphotransferase.
- Mannose 6-P receptors are found in the trans-golgi , which bind to the protein and package them into vesicles for transport.
What happen when if their is a deficiency in the mannose 6-P marker?
I-cell disease
these proteins will accumulate
What are proteoglycans?
contain mainly GAG’s which are special sugars
O-glycoslyation of the core protein
What are glycoproteins?
contain mainly protein and a small amount of sugars which are normally branched
O and N linked
O- linked sugars are bound to what AA’s
serine, theronine, or hydroxy lysine
How are proteins O-linked glycosylated?
- the protein is synthesized on the rER and extrudes into the lumen
- The first sugar is enzymatically linked onto a serine, theronine, or hydroxylysine.
- sugars are add in the golgi by glycosyl transferases
Why is O-linked glycosylation used?
- synthesis of proteoglycans
- glycocalyx components
- blood group components
- mucins
Type O blood?
No sugar linked to Gal of the H substance
Type A blood?
has GalNAc linked to Gal of the H substance
Type B blood?
Has galactose linked to the Gal of the H substance
Type AB blood?
A mix of type A and type B structures
GalNAc and galactose
What kind of proteins are mucins?
they are a glycoprotein
rich in O-linked
What do salivary mucins mainly contain?
contains only one N-acetylglucosamine
this sugar binds NANA, thus a negative charge
How is one way viruses can invade a cell?
they can bind to glycoproteins, which is the first step to infection
How is one way bacteria can invade a cell?
they can bind to surface glycoproteins before entering the cell
E.coli and glycoproteins?
E.coli can attach to a mannose residues that are taken into the cell membrane. first step of infection.
How does H.pylori invade cells?
This bacterium leads to ulcers by interaction with a specific blood group antigen of the gastric epithelium.
What are glycosaminoglycans (GAGs)?
are long, unbranched chains of negatively charged sugars and are often sulfated.
What are proteoglycans?
they mainly contain GAGs and they are part of the extracellular matrix
GAGs are repeated sequences of what sugars?
position 1 = glucuronic acid or iduronic acid
position 2 = glucosamine or galactosamine
characteristics of GAGs?
- they have strong negative charges from the carboxyl and sulfate groups
- bind large amounts of water, thus producing gel like matrix that is part of the ECM
- can compress and relax using water
Functions of GAGs?
- flexible support for the ECM
- molecular sieve
- lubricants
- shock absorber
What is the most abundant GAG? where is it found?
Chondroitins
found in:
- bone
- cartilage
- ligaments
- aorta
explain keratin sulfates?
are special as they contain a sulfated galactose in position-1. They are the most heterogenous regarding their sugars.
found in cartilage and cornea
where are dermatan sulfates found?
skin, blood vessels, and heart valves
What is heparan sulfate used for?
is found in the basement membranes or on cell surfaces used for cell-cell recognition.
contains: sulfated glucuronic acid or iduronic acid
What does heparin do?
It is released from intracellular granules and acts as anticoagulant by ending the blood clotting by facilitating inhibition of thrombin
Why is hyaluronic acid a special GAG?
- it is not sulfated
- not covalently attached to a protein
- Synthesized step by step directly into the extracellular space
- Provides extracellularly the central strand in proteoglycan aggregates
- Hyaluronic acid is connected to the core proteins via link proteins
What is the function of hyaluronic acid?
- vitreous humor in the eye
- synovial fluid of the joints
- cartilage
- loose connective tissues
- neural tube closure during devlopment
- morphogenesis
- wound repair