GLYCOBIOLOGY Flashcards
Glycoconjugates are complex carbohydrates:
hetero-oligosaccharides or hetero-polysaccharides that contain multiple species of monosaccharides.
What are the 3 major classes of glycoconjugates?
Glycoproteins
Proteoglycans
Glycosphingolipids
How do you get from the Fischer projection of D-glucose to the Haworth closed projection? What is formed?
React the 5’OH group with the 1’aldehyde carbonyl group
Forms: B-D-Glucopyranose or a-D-Glucopyranose
Which form of D-glucose is more abundant?
The cyclic closed forms (a- and B-D-glucopyranoses).
The open chain forms are toxic
How do you convert the D-Glucopyranose sugar into L-idopyranose?
Epimerize carbon 5 of D-glucose –> the carbon 5 H is up, and the carbon 6 (CH2OH) is down in both anomers.
- a-L-Idopyranose: carbon 1-OH is up
- B-L-Idopyranose: carbon 1-OH is down
The a-anomeric configs of D- or L- sugars have the carbon 1 -OH group and the carbon 5 H in the __ direction
For a, it’s the same
For B-configurations, they’re opposite
Structure of D-glucose (Glc)
This is the only one you should be able to draw; the others, just know by words
C2 epimer of glucose
C4 epimer of glucose
N-acetylglucosamine (GlcNAc)
C2 hydroxyl gorup modified into an N-acetyl group
D-glucuronic acid (GlcA)
Converting the CH2OH at carbon 6 of D-glucose with a carboxylic acid (COOH) group
L-iduronic acid (IdoA)
Epimerization of carbon 5 of D-glucuronic acid
N-acetylgalactosamine (GalNAc)
C4 epimer of N-acetylglucosamine
Sialic acids / Acylated-neuraminic acids
What are they?
What enzyme cleaves them?
What infection is the enzyme associated with?
Monosaccharides often attached to glycoconjugates
Cleaved from glycoconjugates by sialidase (or Neuraminidase), which are associated with the influenza virus infection
Where does biosynthesis of glycosidic linkages between monosaccharides occur?
What are the requirements?
ER & Golgi
- Activated Nucleotide-Sugar donor
- Sugar acceptor
- Glycosyltransferase
Biosynthesis of lactose in the mammary gland
In the presence of a-lactalbumin (produced in mammary gland), glucose accepts B-galactosyltransferase and forms a glycosidic linkage with galactose –> lactose
In the absence of a-lactalbumin, N-acetylglucosamine accepts B-galactosyltransferase and forms N-acetyllactosamine
N-acetyl glucosamine & glucose are…
sugar acceptors.
Glucose is the one in mammary glands, where a-Lactalbumin is made
N-Acetylglucosamine is the normal acceptor in ordinary tissue
Lactose intolerance
Lactase (B-galactosidase) deficiency -> can’t break down lactose into glucose and galactose
Lactaid contains B-galactosidase
Glycoproteins
glycosylated proteins
may occur via an O-glycosidic linkage (glycosyltransferase sequentially adds sugars to Ser or Thr) or an N-glycosidic linkage (N-glycan changed added to an Asn)
Processing of the N-glycan in the golgi
Canbe processed to either high mannose (neutral) or complex (acidic, containing sialic acid)
type 1 congenital disorders of glycosylation (CDG)
vs
Type 2
- Type 1 CDG disrupts the normal synthesis of the N-linked oligosaccharide precursor or its transfer to proteins
- Type 2 CDG disrupts the processing of the protein-bound oligosaccharide chain
Glycation (nonenzymatic addition of carbs) of HbA creates ___.
The most common and stbale form is ____
Glycation occurs proportionate to the ____
Glycation of HbA –> HbA1
HbA1C is the most stable
Glycation occurs proportionate tot he mean plasma blood [glucose]
Clinical relevance of HbA1C
- Reflects the average blood [glucose] over a period of 2 months (the half-life of an RBC).
- Demonstrates long-term blood [glucose] maintenance
- At normal blood glucose (100mg/dL), HbA1C should be in only 5% of total adult hemoglobin
- Diabetics have > 6.5% of HbA in the HbaA1C form
- Unaffected by day-to-day diabetic compliance or fluctuations in blood glucose levels.
Influenza A / Swine flu subtypes
Subtypes are based upon antigen H/Hemagglutinin (18 subtypes) and antigen N/Neuraminidase (11 subtypes), which are virally encoded envelope proteins
Ex) H1N1
Hemagglutinin/antigen H
A lectin (carbohydrate-binding protein) that specifically binds sialic acid in the membrane of a host cell (respiratory endothelial cells).
Antigen N/ Neuraminidase
Also in the viral envelope, it cleaves sialic acid (N-Acetylneuraminic acid) from the host cell surface
Interaction of viral hemagglutinin and neuraminidase
- Hemagglutinin on the viral envelope interacts with sialic acid on the respiratory endothelial cell’s surface –> entry of virus into the cell
- Virus replicates inside
- Once a new viral particle is released, the hemagglutinin on the viral surface can attach to the host cell membrane
- Neuraminidase cleaves the sialic acid from the host cell surface, allowing the virus to spread to and infect, new hosts
Oseltamivir (Tamiflu)
&
Zanamivir (Relenza)
neuraminidase inhibitors –> prevents the release of new viral particles from the surface of infected cells –> prevents infection spread
Glycosaminoglycans (GAGs) / Mucopolysaccharides
Linear heteropolysaccharides composed of a repeating disaccharide unit: [acidic sugar-amino sugar]n
Usually linked to a core protein to form a proteoglycan, except in hyaluronic acid.
5 divisions of glycosaminoglycans
Hyaluronic acid (HA/hyaluronan)
Chondroitin sulfate (CS)
Dermatan sulfate (DS)
Keratan sulfate (KS)
Heparin & Heparan sulfate (HS)
Proteoglycans - what are they and where are they found?
Core protein + GAGs
in the extracellular matrix
Aggrecan
A chondroitin-sulfate proteoglycan.
- Core protein + ~100 CS + ~30-50 KS
- Can be attached to hyaluronic acid/hyaluronan to form an aggregate
Aggregate
Aggrecan attached to hyaluronic acid
- Extremely hydrophilic & gel-like for the ECM