Carbohydrates Flashcards
(24 cards)
What are carbohydrates?
Saccharides which are polyhydroxylated aldehydes (aldose sugars) or ketones (keto sugars)
General formula of (CH2O)n
Structure of carbohydrates aka sugars
In the Fischer projection, the aldehyde group is always at the top and this carbon is number 1, the hydroxyl (OH) group will be on the carbon furthest from the aldehyde
All natural sugars are in the D-configuration = OH is on the right
Pyranose forms of sugars
When in solution, exist in a cyclic structure
The OH is close to the aldehyde so the alcohol can attack the carbonyl (on aldehyde) to create a new hemiacetal chiral centre (anomeric centre)
The beta anomer (with hydroxyl pointing up) is the more stable than the alpha anomer (with hydroxyl group pointing down)
Position of groups in the chair conformation
Axial positions = substituents are closer together (more crowded)
Equatorial positions = preferred by larger groups, less crowded and more stable
Structure of glucose
- D-glucose is an example of an aldose sugar
- Exists in equilibrium between open chain aldehyde and cyclic pyranose forms
- Beta anomer is most stable in chair conformation with all substituents equatorial
Aldose monosaccharides
- C3 aldoses = D-Glyceraldehyde —> simplest example of an aldose
- C4 aldoses = D-tetroses —> at C2 there’s 2 possible stereoisomers
- C5 aldoses = D-pentoses —> 4 possible stereoisomers
- C6 aldoses = D-hexoses —> 8 possible stereoisomers (pyranose forms and epimers)
What are epimers?
Multiple chiral centres differing in configuration at one centre (usually C2 and C4)
Homo-polymers and their roles
Made up of the same sugar unit
- Starch —> Alpha (1–4) linked D-glucose = energy storage in plants and food for humans
- Cellulose —> Beta (1–4) linked D-glucose = structural component in cell wall of green plants
- Chitin —> Beta (1–4) linked N-acetylglucosamine (GlcNAc) = can interact in additional hydrogen bonding so involved in exoskeleton of shellfish and insects (has an amide group at C2)
(1–4) = linked by carbon 1 of one sugar to C4 of another
Hetero-polymers and their roles
Heparin (made up of different types of sugar)
A sulphated polysaccharide = sugars have sulfate/carboxyl/amide groups
Involved in anticoagulant (prevents blood clots)
What are glycoproteins?
Oligosaccharides are attached to many intracellular and membrane proteins
The sugar molecule in glycoproteins affect the physical properties, stability and interactions of proteins
N-linked glycoproteins
Beta-D-GlcNAc linked to Asn (bond from C1 points up)
Followed by other sugars
O-linked glycoproteins
Alpha-D-GlcNAc linked to either Ser or Thr and then other sugars (Oxygen is pointing down
What are glycolipids?
Oligosaccharides conjugated to lipids & glycoproteins decorate the cell surface with sugars
These serve as recognition elements (attachment proteins) for other cells, bacteria, viruses, hormones and mediate communication, signalling and infection
E.g. Glyceroglycolipids and Glycosphinolipids (have long acyl chains) have a sugar molecule attached instead of a polar head group
Glycoside formation (reactions of acetal functional groups)
O-glycoside formation
- Glucose is protonated at the anomeric position
- Alcohol is now a much better leaving group so water is eliminated
- Oxocarbenium ion is formed and alcohol can attack this from above or below the protonated C=O
- Beta/alpha anomer is formed
- Proton is lost and a glycosidic bond is created
Uses alcohol and Cl catalyst
N-glycoside formation follows the same mechanism
Ether formation via O-alkylation reactions
Can be
SN2
- Strong base (e.g. NaH) deprotonates the alcohol
- Alkoxide anion formed
- Not selective so can alkylate any of the OH groups
- Ends up forming tetra-alkylated product
- No regiocontrol with standard alkylating agents
SN1
- Uses a bulky base such as titryl chloride
- This is more useful as it can selectively react with the primary alcohol group due to steric hinderance
- Generates a carbocation which can be stabilised by resonance into the benzene rings
- Product is only alkylated at the primary alcohol group
What is glycosyltransferase?
An enzyme that controls regiochemistry and anomeric stereochemistry = transfer sugar groups onto substrates
Where in a nucleoside diphosphoso-sugar (a glycosyl donor), the sugar (which is attached to 2 phosphates and a nucleoside) acts as an SN2 nucleophile to produce glycolipids, glycoproteins, Oligosaccharides and polysaccharides
What is the role of glycosidases?
Hydrolyse glycosides using water to give products of inversion (group points down) or retention (group points up) —> (not both)
Specific for donor sugar
Mechanism of inverting beta-galactosidase
- Acidic residue in the active site gets protonated
- Water attacks anomeric centre
- SN2 reaction where the glycosidic bond is cleaved
- Causes inversion so OH group is pointing down
SN1 mechanism is possible via oxocarbenium ion
Mechanism of retaining beta-galactosidase
- Acidic residue in the active site attacks the anomeric centre
- Protonation of OH
- SN2 where alcohol is lost
- Acyl enzyme intermediate formed
- Water is deprotonated in the intermediate to give a second SN2
- Product is retained so OH is pointing up
Double inversion = net retention
How can ester formation occur?
Through O-acylation and phosphorylation reactions
Describe chemical acylation to form esters
- A weak base such as sodium acetate is used
- This deprotonates the primary alcohol on the glucose molecule
- Nucleophilic substitution occurs on the carbonyl
- An acetic anhydride is used to eliminate the tetrahedral intermediate
- Sugar molecule is acetylated but this is non selective
- SO ends up acetylating all the alcohol groups
Describe enzymatic acylation to form esters
- Occurs in nature
- ACP (acyl carrier protein) contains fatty acid chain
- Acyltransferase (LpxA) transfers the fatty acid chain from ACP to UDP-GlcNAc
- This is regioselective so will selectively isolate the OH on the C3 in the sugar
Describe enolate chemistry
Rearrangement of glucose to fructose
Glucose (an aldose sugar) can be rearranged to a Fructose (a ketose sugar) via use of NaOH & H2O
Describe imine formation
Reaction of aldehydes and ketones with amines
- Protonation of aldehyde to make it a more reactive nucleophile
- Lysine residue of haemoglobin attacks the positive carbonyl
- This forms a tetrahedral intermediate
- Water is eliminated to produce an iminium ion
- This is deprotonated to give an imine
- On the imine, haemoglobin is attached by an imine bond
- This undergoes rearrangement to form a ketone = irreversible
