17 - Carbohydrates Flashcards
What are some forms of glycans?
Oligosaccharides, polymers, mixed polymers, and free glycans
What are the functions of oligosaccharides?
Molecular recognition
What are the functions of carbohydrate polymers?
Structure, energy storage
What are the functions of carbohydrate mixed polymers?
Structure, information
What are the functions of free glycans?
Signaling, osmoprotection
What are some examples of biological walls?
Cellulose (plants), chitin (fungi), and peptidoglycan (bacteria)
What are some examples of internal molecular recognition?
Glycoconjugates on lymphocytes interact with P-selectin on endothelial cells to recruit them to the site of inflammation
What are some examples of extrinsic molecular recognition?
Hemagglutinin on influenza virus recognizes glycosylated receptors to allow viral entry
What is a glycoconjugate?
A glycan connected to something else (usually a protein)
What chemical interactions are important for carbohydrates and why?
H-bonds (lots of hydroxyls)
What are some examples of regulatory roles of glycans?
GlcNAc modifications can change protein function, localization, recognition, and stability
How do glycans participate in quality control?
Glycosylated nascent proteins in the ER determine folding
What is an aglycan?
Something that is not a glycan (protein, lipid, etc.)
What is the general structure of a monosaccharide?
A series of chiral hydroxymethylene units
What is an aldose?
A monosaccharide with an aldehyde carbonyl group
What is a ketose?
A monosaccharide with a ketone carbonyl group
If glucose has 6 carbons and an aldehyde, what is another name for glucose?
Aldohexose
How does a monosaccharide go from a linear form to a cyclic form?
One of the OH acts as a nucleophile, and the carbonyl acts as an electrophile to create a ring
What determines which hydroxyl will attack the carbonyl in the cyclization reaction?
Produce a stable ring (5 or 6 membered ring)
What is the structure of an acetal?
-C-(OR),(OR)
What is the structure of a hemiacetal?
-C-(OR),(OH)
When the cyclic glycan is formed, what functional group is formed?
A hemiacetal
What is the importance of a hemiacetal?
It is reactive
Which form of glucose is dominant in solution and why?
Cyclic form, because it is more stable as a ring
True or false: glucose only exists as a ring in solution
False: the linear and cyclic forms are in equilibrium
What is the anomeric carbon?
The carbon from the carbonyl
What is the stereochemistry of the anomeric carbon?
It can be either equatorial or axial (depends on nucleophilic attack)
What is the importance of the stereochemistry of the anomeric carbon?
It strongly influences structure of monosaccharides modified at this carbon, and therefore biological function
What is the alpha configuration of a glycan?
C1 and C5 have the same configuration (R/S)
What is the beta configuration of a glycan?
C1 and C5 have the different configuration (R/S)
For glucose, what is alpha?
Anomeric carbon is axial
For glucose, what is beta?
Anomeric carbon is equatorial
True or false: all alpha is axial, all beta is equatorial
False: alpha and beta are relative to the configuration of the C5 carbon
What does furanose look like?
Pentagon with an O in the ring
What does pyranose look like?
Hexagon with an O in the ring
What are epimers?
Monosaccharide stereoisomers (differ at one position)
What are some examples of epimers?
Glucose and galactose, glucose and mannose
What is a glycosidic bond?
The bond between the anomeric carbon on one monosaccharide and the hydroxyl on another
What is the importance of the glycosidic bond?
It is the most flexible part of the disaccharide structure
How are glycans “read”?
From nonreducing end to reducing end?
What is the reducing end of a glycan?
The place with the free anomeric carbon (no glycosidic bond)
What is the nonreducing end of a glycan?
The place without the free anomeric carbon (glycosidic bond)
True or false: all glycans have a reducing end
False: if two anomeric carbons are linked together, then there is no reducing end
What is the same between cellulose and starch?
They both are composed of 1,4-glycosidic bonds
What is different between cellulose and starch?
They have different stereochemistry (starch is alpha, cellulose is beta)
What is the difference in structure between cellulose and starch?
Starch twists, while cellulose is in sheets
How are glycosidic bonds different from phosphodiester or peptide bonds?
They have many different connectivities (regiochemistry) and configurations (stereochemistry)
What is unique about glycan biosynthesis?
It is not template directed
What determines the glycan isoform on a protein?
The localization and expression of glycosyltransferases
What are the three steps of the biosynthesis of glycoconjugates?
- Activation of nucleotide sugars (in cytosol)
- Transport of nucleotide sugars into ER and Golgi
- Transfer of nucleotide sugars to an acceptor (protein, lipid, glycan, etc.)
What is the consequence of non-template directed biosynthesis of glycans?
A protein can have a heterogeneous mixture of glycans
What sugars are used for activation?P
UDP/GDP sugars (with the exception of CMP-Sia) (can also have lipid sugars)
What enzyme transfers sugars to form oligosaccharides?
Glycosyltransferases
What reaction do glycosyltransferases catalyze?
NDP-sugar donor + substrate acceptor –> NDP + sugar substrate
Where does glycosylation occur?
In cytosol, ER, Golgi, mitochondria, etc.
Where are N-glycoproteins produced?
In the ER/Golgi
What is the N-glycoprotein linked to?
An Asn residue (oligosaccharide-N-Asn-protein)
What is the consensus sequence for N-glycosylation?
Asn-X-Ser/Thr (attach to Asn)
Where are N-glycoproteins often found?
On the surface of secreted or membrane proteins
How can N-glycoproteins differ?
By the branches of glycans present
How do ER lectins use N-glycans?
They recognize the glycan to promote protein folding
What is a lectin?
A protein that recognizes a glycan
What does CRT and CNX stand for?
Calreticulin and calnexin
How do CRT and CNX work?
They only recognize the terminal glucose in N-glycans
What happens to CRT and CNX if there is deglucosylation?
The peptide is released (and hopefully folded)
How do CRT and CNX recognize if a protein needs to be refolded?
If it is re-glucosylated
What is the consensus sequence for O-glycosylation?
Ser/Thr - O - oligosaccharide
What does “O-GalNAc” mean?
GalNAc on 1st Ser/Thr residue
What is mucin?
A highly O-(GalNAc)-glycosylated protein
What is the purpose of VNTR in mucin?
It is rich in Ser, Thr, and Pro, so it becomes widely O-glycosylated
What is the function of mucin?
Shield against physical and chemical damage, protect against infection
Where does O-glycosylation occur?
In the cytosol
How does Chagas parasite hide from host cell immunity?
It has trans-sialidase enzyme to transfer Sia from host protein, and protect from recognition (avoid recognizing Gal at end of mucin)
What is the native configuration of Chagas parasite?
It has Gal at the end of its mucin (can be detected by antibodies)
Where does O-GlcNAc occur?
In cytosol, nucleus, and mitochondria
What are some properties of O-GlcNAc signaling?
It is reversible, highly dynamic, and competes with other processes
How is O-GlcNAc a metabolic sensor?
- UD for nucleotide metabolism
- P for overall energy
- Glc for glucose metabolism
- N for nitrogen metabolism
- Ac for fatty acid metabolism
How does O-GlcNAc change the rate of glycolysis?
As O-GlcNAc increases, the rate of glycolysis decreases
How does O-GlcNAc regulate glycolysis?
By decreasing activity of PFK
How does O-GlcNAc regulate PFK?
It competes for binding for the product FBP at the same binding site (Ser529)
How does cancer alter glycosylation?
- Altered branching of N-glycans
- Higher expression of O-linked glycans
- Higher surface Sia (malignancy, reduced attachment)
How does Tamiflu work?
It mimics H-bond interacts to fight the flu
What does Tamiflu do?
It competes with host sialic acid that the virus needs to release new particles
Where is hyaluronic acid found?
In the ECM
