Vitamins, Allostery, and
Sugars
Andy Howard
Introductory Biochemistry, Spring 2008
26 February 2008
1
Now we’ll study sugars!

But first, we’ll finish discussing
vitamins, and we’ll pick up a
specific protein-related topic from
chapter 5—namely, allostery
Biochemistry: Vitamins; Carbohydrates I
p. 2 of 58
What we’ll discuss
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Vitamins
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Water-soluble
Fat-Soluble
Allostery
Carbohydrates
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Carbohydrates
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Glycosides
Polysaccharides
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Sugar Concepts
Monosaccharides
Oligosaccharides
Biochemistry: Vitamins; Carbohydrates I
Starch & glycogen
Cellulose and chitin
Glycoconjugates
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Proteoglycans
Peptidoglycans
Glycoproteins
p. 3 of 58
Vitamins: broad classifications

Water-soluble vitamins
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Coenzymes or coenzyme precursors
Non-coenzymic metabolites
Fat-soluble vitamins
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Antioxidants
Other lipidic vitamins
Biochemistry: Vitamins; Carbohydrates I
p. 4 of 58
Are all nutrients that we can’t
synthesize considered
vitamins?
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No:
If it’s required in large quantities,
it’s not a vitamin
By convention, essential fatty acids like
arachidonate aren’t considered vitamins
Biochemistry: Vitamins; Carbohydrates I
p. 5 of 58
Ascorbate

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Vitamin in primates, some rodents
Synthesizable in most other vertebrates
Involved in collagen
Reduced form acts as reducing agent during
hydroxylation of collagen:
proline  hydroxyproline, lysine  hydroxylysine
Deficiency gives rise to inadequate collagen scurvy
Biochemistry: Vitamins; Carbohydrates I
p. 6 of 58
Vitamin A (retinol)
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3 forms varying in terminal polar group
Involved in signaling and receptors
b-carotene is nonpolar dimer
Biochemistry: Vitamins; Carbohydrates I
p. 7 of 58
Vitamin D

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Several related forms
Hormones involved in
Ca2+ regulation
Figure courtesy
Cyberlipid
Biochemistry: Vitamins; Carbohydrates I
p. 8 of 58
Vitamin E (a-tocopherol)


Phenol can undergo 1e- oxidation to
moderately stable free radical
Antioxidant activity prevents damage to
fatty acids in membranes
phenol
Fig. Courtesy
UIC pharmacy program
Biochemistry: Vitamins; Carbohydrates I
p. 9 of 58
Vitamin K (phylloquinone)


Involved in synthesis of
proteins involved in
blood coagulation
Reduced form involved
as reducing agent in
carboxylation reaction
on glu sidechains
Figure courtesy
Cyberlipid
Biochemistry: Vitamins; Carbohydrates I
p. 10 of 58
Allostery

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This is covered at the end of chapter 5,
but somehow we missed it… here goes.
Formal definition:
alterations in protein function that occur
when the structure changes upon binding
of small molecules
In practice: often the allosteric effector is
the same species as the substrate
Biochemistry: Vitamins; Carbohydrates I
p. 11 of 58
v0
[S]
What it means for enzymes

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Non-enzymatic proteins can be
allosteric:
hemoglobin’s affinity for O2 is
influenced by the binding of O2 to
other subunits
In enzymes: non-MM kinetics (often
sigmoidal) when the allosteric
activator is also the substrate
Biochemistry: Vitamins; Carbohydrates I
p. 12 of 58
R and T states
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Enzyme with multiple substrate binding sites
is in T (“tense”) state in absence of substrate
Binding of substrate moves enzyme into R
(“relaxed”) state where its affinity for substrate
at other sites is higher
Velocity can then rise rapidly as function of [S]
Once all the enzyme is converted to R state,
ordinary hyperbolic kinetics take over
Biochemistry: Vitamins; Carbohydrates I
p. 13 of 58
Other effectors can influence
RT transitions

Post-translational covalent modifiers
often influence RT equilibrium
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Phosphorylation can stabilize either the
R or T state
Binding of downstream products can
inhibit TR transition
Binding of alternative metabolites can
stabilize R state
Biochemistry: Vitamins; Carbohydrates I
p. 14 of 58
Why does that make sense?

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Suppose reactions are:
(E)
ABCD
Binding D to enzyme E that converts A to
B will destabilize R state, limiting
conversion of A to B and (ultimately)
reducing / stabilizing [D]: homeostasis!
Biochemistry: Vitamins; Carbohydrates I
p. 15 of 58
Alternative pathways
• Often one metabolite has two possible
fates:
BCD
A
HIJ
• If we have a lot of J around, it will bind to
the enzyme that converts A to B and
activate it; that will balance D with J!
Biochemistry: Vitamins; Carbohydrates I
p. 16 of 58
Carbohydrates
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These are polyhydroxylated aldehydes and
ketones, many of which can exist in cyclic forms
General monomeric formula (CH2O)m, 3 < m < 9
With one exception (dihydroxyacetone) they
contain chiral centers
Highly soluble
Can be oligomerized and polymerized
Most abundant organic molecules on the planet
Biochemistry: Vitamins; Carbohydrates I
p. 17 of 58
How do we measure solubility
for very soluble compounds?
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(Note: this is not a serious chemical topic: it’s an
example of how statistics can be abused…)
The assertion is that, with highly soluble
compounds like sugars, it’s difficult to use
conventional approaches to compare their
solubilities
The suggestion is that we might use the amount
of time it takes to dissolve (for example) 50g of
solute in 100mL of cold water: if it’s fast, the
solute is more soluble than if it’s slow.
Biochemistry: Vitamins; Carbohydrates I
p. 18 of 58
Solubility measured by
dissolution time
6
5
4

Assertion: more polar
groups means shorter
dissolution time for a given
class of compounds
3
2
1
Time required for dissolution
Biochemistry: Vitamins; Carbohydrates I
p. 19 of 58
What if we
extrapolate
to n=6?
Extrapolated
6
point
5
4
3
2
1
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We get a negative dissolution
time!
That is, the solid goes into
solution 6 seconds before we
put it in the water!
This causes serious
psychological problems (what
if I change my mind?) and
philosophical problems (is this
pre-ordained?)
Observed
points
Time required for dissolution
Biochemistry: Vitamins; Carbohydrates I
p. 20 of 58
Whose idea is this?
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Isaac Asimov, that’s who!
“The endochronic properties of resublimated
thiotimolene”:
Astounding Science Fiction, ~1948
His point: extrapolations and other misuses of
statistics are dangerous
Benjamin Disraeli (popularized by Mark Twain):
There are three kinds of untruth:
lies, damn lies, and statistics.
Biochemistry: Vitamins; Carbohydrates I
p. 21 of 58
Aldoses & ketoses
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If the carbonyl moiety is at
the end carbon
(conventionally counted as
1), it’s an aldose
If carbonyl is one carbon
away (counted as 2), it’s a
ketose
If it’s two or more carbons
from the end of the chain,
it’s not a sugar
Biochemistry: Vitamins; Carbohydrates I
p. 22 of 58
Simplest monosaccharides
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Glyceraldehyde and
dihydroxyacetone
Only glyceraldehyde is chiral:
D-enantiomer is more plentiful in
biosphere
All longer sugars can be regarded
as being built up by adding
-(CHOH)m-1 to either
glyceraldehyde or
dihydroxyacetone, just below C2
Biochemistry: Vitamins; Carbohydrates I
p. 23 of 58
How many aldoses are there?
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Every -(CHOH) in the interior offers one
chiral center
An m-carbon aldose has (m-2) internal
-(CHOH) groups
Therefore: 2m-2 aldoses of length m
For m=3, that’s 21=2; for m=6, it’s 24=16.
Biochemistry: Vitamins; Carbohydrates I
p. 24 of 58
How many ketoses are there?
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Every -(CHOH) in the interior offers
one chiral center
An m-carbon ketose has (m-3) internal
-(CHOH) groups
Therefore: 2m-3 ketoses of length m
For m=3, that’s 20 = 1; for m=6, that’s
23=8.
Biochemistry: Vitamins; Carbohydrates I
p. 25 of 58
Review: stereochemical
nomenclature
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Stereoisomers: compounds with identical
covalent bonding apart from chiral connectivity
Enantiomers: compounds for which the opposite
chirality applies at all chiral centers
Epimers: compounds that differ in chirality at
exactly one chiral center
One chiral center: enantiomers are epimers.
> 1 chiral center: enantiomers are not epimers.
Biochemistry: Vitamins; Carbohydrates I
p. 26 of 58
Example: 2 chiral centers

Chiral centers u,v; compounds A,B,C,D
Compound
Stereo
@u
Stereo
@v
Enantio- Epimer
morph of of
A
+
+
D
B,C
B
+
-
C
A,D
C
-
+
B
A,D
D
-
-
A
B,C
Biochemistry: Vitamins; Carbohydrates I
p. 27 of 58
Properties
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Enantiomers have identical physical
properties (MP,BP, solubility, surface
tension…) except when they interact with
other chiral molecules
Stereoisomers that aren’t enantiomers
can have different properties; therefore,
they’re often given different names
Biochemistry: Vitamins; Carbohydrates I
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Sugar nomenclature
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All sugars with m≤7 have specific names
apart from their enantiomeric (L or D)
designation, e.g. D-glucose, L-ribose.
Biochemistry: Vitamins; Carbohydrates I
p. 29 of 58
Fischer projections
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Convention for drawing openchain monosaccharides
If the hydroxyl comes off
counterclockwise relative to
the previous carbon, we draw
it to the left;
Clockwise to the right.
Biochemistry: Vitamins; Carbohydrates I
Emil
Fischer
p. 30 of 58
Cyclic sugars
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Sugars with at least four carbons can
readily interconvert between the openchain forms we have drawn and fivemembered(furanose) or six-membered
(pyranose) ring forms in which the
carbonyl oxygen becomes part of the ring
There are no C=O bonds in the ring forms
Biochemistry: Vitamins; Carbohydrates I
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Furanoses
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Formally derived from
structure of furan
Hydroxyls hang off of the
ring; stereochemistry
preserved there
Extra carbons come off at 2
and 5 positions
Biochemistry: Vitamins; Carbohydrates I
1
5
2
4
3
furan
p. 32 of 58
1
Pyranoses
6
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Formally derived from
structure of pyran
Hydroxyls hang off of the
ring; stereochemistry
preserved there
Extra carbons come off at 2
and 6 positions
Biochemistry: Vitamins; Carbohydrates I
2
3
5
4
pyran
p. 33 of 58
How do we cyclize a sugar?
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Formation of an internal hemiacetal or
hemiketal (see a few slides from here)
by conversion of the carbonyl oxygen
to a ring oxygen
Not a net oxidation or reduction;
in fact it’s a true isomerization.
The molecular formula for the cyclized
form is the same as the open chain
form
Biochemistry: Vitamins; Carbohydrates I
p. 34 of 58
Family tree of aldoses
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Simplest: D-, L- glyceraldehyde (C3)
Add —CHOH: D,L-threose, erythrose (C4)
Add —CHOH:
D,L- lyxose, xylose, arabinose, ribose (C5)
Add —CHOH:
D,L-talose, galactose, idose, gulose,
mannose, glucose, altrose, allose (C6)
Biochemistry: Vitamins; Carbohydrates I
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Family tree of ketoses
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Simplest: dihydroxyacetone (C3)
Add —CHOH: D,L-erythrulose (C4)
Add —CHOH:
D,L- ribulose, xylulose (C5)
Add —CHOH:
D,L-sorbose, tagatose, fructose, psicose
Biochemistry: Vitamins; Carbohydrates I
p. 36 of 58
Haworth projections

…provide a way of
keeping track the chiral
centers in a cyclic sugar,
as the Fisher projections
enable for straight-chain
sugars
Biochemistry: Vitamins; Carbohydrates I
Sir Walter
Haworth
p. 37 of 58
O
The anomeric carbon
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C
In any cyclic sugar
(monosaccharide, or single unit of
an oligosaccharide, or
polysaccharide) there is one
carbon that has covalent bonds to
two different oxygen atoms
We describe this carbon as the
anomeric carbon
Biochemistry: Vitamins; Carbohydrates I
p. 38 of 58
O
a-Dglucopyranose
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One of 2 possible
pyranose forms of Dglucose
There are two
because the anomeric
carbon itself becomes
chiral when we
cyclize
Biochemistry: Vitamins; Carbohydrates I
p. 39 of 58
b-Dglucopyranose
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Differs from aD-glucopyranose only
at anomeric
carbon
Biochemistry: Vitamins; Carbohydrates I
p. 40 of 58
Count carefully!
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It’s tempting to think that hexoses are
pyranoses and pentoses are furanoses;
But that’s not always true
The ring always contains an oxygen, so
even a pentose can form a pyranose
In solution: pyranose, furanose, openchain forms are all present
Biochemistry: Vitamins; Carbohydrates I
p. 41 of 58
Substituted monosaccharides
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Substitutions on the various positions
retain some sugar-like character
Some substituted monosaccharides are
building blocks of polysaccharides
Amination, acetylamination,
carboxylation common
O
OOH
HO
HO
O
OH
HNCOCH3
HO
O
HO
Biochemistry: Vitamins; Carbohydrates I
OH
HO
p. 42 of 58
Acetals and ketals
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Hemiacetals and hemiketals are compounds that have an
–OH and an –OR group on the same carbon
Cyclic monosaccharides are hemiacetals & hemiketals
Acetals and ketals have two —OR groups on a single
carbon
Acetals and ketals are found in glycosidic bonds
Biochemistry: Vitamins; Carbohydrates I
p. 43 of 58
Sucrose: a glycoside
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A disaccharide
Linkage is between
anomeric carbons of
contributing
monosaccharides,
which are glucose
and fructose
Biochemistry: Vitamins; Carbohydrates I
p. 44 of 58
Reducing sugars
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Sugars that can undergo ring-opening to
form the open-chain aldehyde compounds
that can be oxidized to carboxylic acids
We describe those as reducing sugars
because they can reduce metal ions or
amino acids in the presence of base
Benedict’s test:
2Cu2+ + RCH=O + 5OH- 
Cu2O + RCOO- + 3H2O
Cuprous oxide is red and insoluble
Biochemistry: Vitamins; Carbohydrates I
p. 45 of 58
Ketoses are reducing sugars

In presence of base a ketose can
spontaneously rearrange to an aldose
via an enediol intermediate, and then
the aldose can be oxidized.
Biochemistry: Vitamins; Carbohydrates I
p. 46 of 58
Sucrose: not a reducing sugar
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Both anomeric carbons
are involved in the
glycosidic bond, so they
can’t rearrange or open
up, so it can’t be oxidized
Bottom line: only sugars
in which the anomeric
carbon is free are
reducing sugars
Biochemistry: Vitamins; Carbohydrates I
p. 47 of 58
Reducing & nonreducing ends
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Typically, oligo and polysaccharides have a
reducing end and a nonreducing end
Non-reducing end is the sugar moiety whose
anomeric carbon is involved in the glycosidic
bond
Reducing end is sugar whose anomeric carbon
is free to open up and oxidize
Enzymatic lengthening and degradation of
polysaccharides occurs at nonreducing end or
ends
Biochemistry: Vitamins; Carbohydrates I
p. 48 of 58
Nucleosides
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Anomeric carbon of
ribose (or deoxyribose) is
linked to nitrogen of RNA
(or DNA) base
(A,C,G,T,U)
Generally ribose is in
furanose form
This is an example of an
N-glycoside
Biochemistry: Vitamins; Carbohydrates I
Diagram courtesy of
World of Molecules
p. 49 of 58
Polysaccharides
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Homoglycans: all building blocks same
Heteroglycans: more than one kind of
building block
No equivalent of genetic code for
carbohydrates, so long ones will be
heterogeneous in length and branching,
and maybe even in monomer identity
Biochemistry: Vitamins; Carbohydrates I
p. 50 of 58
Storage polysaccharides
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Available sources of glucose for energy
and carbon
Long-chain polymers of glucose
Starch (amylose and amylopectin):
in plants, it’s stored in 3-100 µm granules
Glycogen
Branches found in all but amylose
Biochemistry: Vitamins; Carbohydrates I
p. 51 of 58
Amylose
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Unbranched, a-14 linkages
Typically 100-1000 residues
Not soluble but can form hydrated
micelles and may be helical
Amylases hydrolyze a-14 linkages
Diagram courtesy
Langara College
Biochemistry: Vitamins; Carbohydrates I
p. 52 of 58
Amylopectin
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Mostly a-14 linkages; 4% a-16
Each sidechain has 15-25 glucose
moieties
a-16 linkages broken down by
debranching enzymes
300-6000 total glucose units per
amylopectin molecule
One reducing end, many nonreducing
ends
Biochemistry: Vitamins; Carbohydrates I
p. 53 of 58
Glycogen
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Principal storage form of glucose in
human liver; some in muscle
Branched (a-14 + a few a-16)
More branches (~10%)
Larger than starch: 50000 glucose
One reducing end, many nonreducing
ends
Broken down to G-1-P units
Built up from G-6-P  G-1-P  UDPGlucose units
Biochemistry: Vitamins; Carbohydrates I
p. 54 of 58
Glycogen
structure
Biochemistry: Vitamins; Carbohydrates I
p. 55 of 58
Structural polysaccharides
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Insoluble compounds designed to
provide strength and rigidity
Cellulose: glucose b-14 linkages
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Rigid, flat structure: each glucose is upside
down relative to its neighbors
300-15000 glucose units
Found in plant cell walls
Resistant to most glucosidases
Cellulases found in termites,
ruminant gut bacteria
Chitin: GlcNAc b-14 linkages:
exoskeletons, cell walls
Biochemistry: Vitamins; Carbohydrates I
p. 56 of 58
Glycoconjugates
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Poly or oligosaccharides covalently
linked to proteins or peptides
Generally heteroglycans
Categories:
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Proteoglycans
(protein+glycosaminoglycans)
Peptidoglycans (peptide+polysaccharide)
Glycoproteins (protein+oligosaccharide)
Biochemistry: Vitamins; Carbohydrates I
p. 57 of 58
Proteoglycans:
Glycosaminoglycans
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Unbranched heteroglycans of repeating
disaccharides
One component is
GalN, GlcN, GalNAc, or GlcNAc
Other component: an alduronic acid
—OH or —NH2 often sulfated
Found in cartilage, joint fluid
Biochemistry: Vitamins; Carbohydrates I
p. 58 of 58