Carbohydrates
CH339K
What Makes a Carbo a Carbo?
Overall formula
CH 2On
Where n ≥ 3
Etymology: From their general formula
Cn(H2O)n; they were once thought to be
hydrates of carbon.
Simplest Carbos: N=3
2 Tautomers
Tautomers are isomers of organic compounds
that readily interconvert by a chemical
reaction called tautomerization. (Wikipedia)
Vertical bonds go into the plane of the projection
Horizontal bonds emerge from the plane of projection
Glyceraldehyde exists as a pair of enantiomers
Enantiomers are non-superimposable mirror
images
R-S Nomenclature (for the Organic guys)
With n > 3, you can form diastereomers
Diastereomers are stereoisomers that are not mirror
images
Hemiacetals and Hemiketals
An aldehyde or a ketone can react
wth an alcohol
Ring formation
Ring formation
in a ketose
Anomers
Differ at the hemiacetal or hemiketal carbon
a-D-Glucose
b-D-Glucose
Furanoses and Pyranoses
Multiple possible rings in a C6-Ketose
Multiple Possible Rings in a C5-Aldose
Ring pucker
Epimers
Differ at only one carbon, but not the anomeric
carbon
Sugar Derivatives
-2H+,e-
+H2O
aldonolactone
Aldonic acid
Cu2+
+NH3, -H2O
Acetic
anhydride
Alduronic acid
Amino sugar
Substituted
Amino sugar
Sugar Derivatives
Glycosides
Glycoside: Any of a group of organic compounds that
yield a sugar and one or more nonsugar substances on
hydrolysis.
Natural Glycosides
Amygdalin is a poison found in the seeds
of bitter almonds. It releases cyanide
upon hydrolysis.
Amygdalin is also known as Laetrile or
“Vitamin B17,” a quack (excuse me,
“alternative”) cancer treatment.
Natural Glycosides
Digitoxin is used as a heart
stimulant in medicine; related
componds are used as poisons
in murder mysteries
Polymerization
Activation – couple to UDP
Disaccharides
Storage Polysacharides
amylopectin
Amylose Structure
Iodine Test for Starch – Molecular Basis
I2 + I-  I3
Amylopectin: a-1,4 + a-1,6
Glycogen : a-1,4 + a-1,6
Glycogen in liver
cells – stained with
carmin
Storage Polysaccharides
Polysaccharide
Linkage
Branching
Size (residues)
Amylose
a-1,4
unbranched
Up to 5,000
Amylopectin
a-1,4 and a-1,6
25-30 residues
Up to 1,000,000
Glycogen
a-1,4 and a-1,6
8-12 residues
Up to 50,000
Structural Polysaccharides
Cellulose
Cellulose complexes
β(1-4) linkages form flat sheets
• analogous to β-sheets in proteins
• multiple hydrogen bonds between strands.
Chitin
Insect cuticles
Self-Nonself Recognition – Blood Groups
Bacterial Cell Walls
Gram +
Staphylococcus aureus
Gram -
Escherischia coli
Bacterial Cell Walls
Gram -
Gram +
Bacterial Cell Walls – another view
Peptidoglycan Components
E. coli
S. aureus
What the heck is diaminopimelate?
Lysine with an extra
carboxyl attached to Ce.
Transpeptidase cross-links the
individual chains
Gram -
Gram +
Cross Linking
E. Coli
S. aureus
Spore formation
Figure 1. Stages of sporulation. (A)
Stage 0/I, (B) stage II, (C) stage
III, (D) stage IV, (E) released spore.
The hatched line around the
spore in panels D and E is the coat.
From: Cell. Mol. Life Sci. 59 (2002)
Bacillus anthracis
Production
Do not try this at
home!!!!!
1. It will not work as
shown
2. You will die
3. Everyone you
know will go to
Gitmo
Delivery
The M33 500-lb biological cluster bomb, which
held 108 of the M114 bombs.
Photograph: Chemical and Biological Defense Command
Historical Research and Response Team, Aberdeen Proving
Ground, Md.
Pilot anthrax plant at Ft. Detrick,
MD (shut down in 1969)
Al Hakam “Single-Cell Protein”
Plant (demolished under UN
supervision, 1996)
Whoopsie!
1979 – Sverdvlosk
66 people die
Aerosol plume from
“Military Compound
19”
Somebody left the
vent to the outside
open.
b-Lactams
This carbon forms covalent bond with active-site
serine on transpeptidase enzyme
Glycosaminoglycans
Aka Mucopolysaccharides
- Unbranched polysaccharides
- Repeating disaccharide
- Hexose linked to aminohexose
- Typically with many negative
charges
-Acidic
-Slimy
Structure
Name/Composition
Hyaluronates:
composed of D-glucuronate + GlcNAc
linkage is b(1, 3)
Localization
synovial fluid, vitreous
humor,
ECM of loose connective
tissue
Dermatan sulfates:
composed of L-iduronate (many are
sulfated) + GalNAc-4-sulfate
linkages is b(1, 3)
skin, blood vessels, heart
valves
Chondroitin 4- and 6-sulfates :
composed of D-glucuronate +
GalNAc-4- or 6-sulfate
linkage is b(1, 3)
(the figure contains GalNAc 4-sulfate)
cartilage, bone, heart valves
most abundant GAG
Heparin and Heparan sulfates:
composed of D-glucuronate-2-sulfate
(or iduronate-2-sulfate) + N-sulfo-Dglucosamine-6-sulfate
linkage is a(1, 4)
(heparans have less sulfate than
heparins)
Heparin
component of intracellular
granules of mast cells
lining the arteries of the
lungs, liver and skin
Heparan Sulfate
basement membranes,
components of cell surfaces
cornea, bone,
cartilage aggregated with
chondroitin sulfates
Heparin
more sulfated than heparan
sulfates
Heparan Sulfate
contains higher acetylated
glucosamine than heparin
Keratan sulfates:
composed of galactose + GlcNAc-6sulfate
linkage is b(1, 4)
Comments
large polymers, shock
absorbing
cornea, bone,
cartilage aggregated with
chondroitin sulfates
Proteoglycans
• Cell surface or extracellular matrix
• Glycosaminoglycan(s) bound to core protein
• Noncovalent attachments to help bind
extracellular matrix
Disease from Failure to Metabolize Glycosaminoglycans
(One example of many)
Disease
Hurler syndrome
Deficient
enzyme
Accumulated
products
α-L-iduronidase Heparan sulfate
Dermatan sulfate
Symptoms
Incidence
Mental retardation 1 in 100.000
Micrognathia
Coarse facies
Macroglossia
Retinal
degeneration
Corneal clouding
Cardiomyopathy
Hepatosplenomegal
y
Proteoglycan - Photo
Glycoproteins
Glycoprotein Functions
Function
Glycoproteins
Structural molecule
Collagens
Lubricant and protective agent
Mucins
Transport molecule
Transferrin, ceruloplasmin
Immunologic molecule
Immunoglobins, histocompatibility antigens
Hormone
Chorionoic gonadotropin, thyroid-stimulating hormone
(TSH)
Enzyme
Various, eg, alkaline phosphatase
Cell attachment-recognition site
Various proteins involved in cell-cell (eg, sperm-oocyte),
virus-cell, bacterium-cell, and hormone cell interactions
Antifreeze
Certain plasma proteins of coldwater fish
Interact with specific carbohydrates
Lectins, selectins (cell adhesion lectins), antibodies
Receptor
Various proteins involved in hormone and drug action
Affect folding of certain proteins
Calnexin, calreticulin
Regulation of development
Notch and its analogs, key proteins in development
Hemostasis (and thrombosis)
Specific glycoproteins on the surface membranes of
platelets
N-Linked Glycosylation
•
•
•
•
All eukaryotes make N-linked glycoproteins
Usually Cotranslational
Consensus sequence Asn – X – Ser/Thr
Usually when there’s an accessible loop in
the folding protein structure
N-Linked Glycosylation (cont.)
• Core oligosaccharide synthesized on cytoplasmic side of ER
• Attached to dolichol in ER membrane
• Core oligo transferred to lumen of ER
• Core oligo transferred to protein
• Further processing occurs in ER / Golgi
N-Linked Glycosylation
O-Linked Glycosylation
•
•
•
•
•
•
•
True posttranslational modification
No oligo precursor
Frequently starts with GalNAc
Secretory cells
Zona pellucida around mammalian eggs
Hematopoeisis
Inflammatory response
Common (not
universal!!) core
Frozen Fish (Not!)
Chaenocephalus aceratus