Carbohydrates III;
Lipids I
Andy Howard
Introductory Biochemistry, Fall 2010
21 September 2010
As delivered by Nick Menhart
Biochem: Carbo III, Lipids I
09/21/2010
Sugar Complexes and Lipids


Sugars form complexes with proteins
and lipids
Lipids are critical as energy storage
molecules and as components of
membranes
09/21/2010
Biochem: Carbo III, Lipids I
p. 2 of 50
Plans for Today

Glycoconjugates




Proteoglycans
Peptidoglycans
Glycoproteins


Classes of lipids
Fatty acids
Triacylglycerols
09/21/2010
Lipids, continued



Lipids





Biochem: Carbo III, Lipids I
Glycerophospholipids
Plasmalogens
Sphingolipids
Isoprenoids
Steroids
Other lipids
p. 3 of 50
Glycoconjugates



Poly or oligosaccharides
covalently linked
to proteins or peptides
Generally heteroglycans
Categories:



Image courtesy
Benzon Symposia
Proteoglycans
(protein+glycosaminoglycans)
Peptidoglycans (peptide+polysaccharide)
Glycoproteins (protein+oligosaccharide)
09/21/2010
Biochem: Carbo III, Lipids I
p. 4 of 50
Proteoglycans:
Glycosaminoglycans





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
09/21/2010
Biochem: Carbo III, Lipids I
p. 5 of 50
Proteoglycans
in cartilage




Highly hydrated,
voluminous
Mesh structure
(fig.7.36 or this fig.
from Mathews & Van
Holde)
Aggrecan is major
proteoglycan
Typical of
proteoglycans in that
it’s extracellular
09/21/2010
Biochem: Carbo III, Lipids I
p. 6 of 50
Peptidoglycans
(G&G fig. 7.29)




Polysaccharides linked to small proteins
Featured in bacterial cell walls:
alternating GlcNAc + MurNAc
linked with -(14) linkages
Lysozyme hydrolyzes these polysaccharides
Peptide is species-specific:
often contains D-amino acids
09/21/2010
Biochem: Carbo III, Lipids I
p. 7 of 50
Peptidoglycans
in bacteria




Gram-negative: thin peptidoglycan layer
separates two phospholipid bilayer
membranes
Gram-positive: only one bilayer, with thicker
peptidoglycan cell wall outside it
Gram stain binds to thick wall, not thin layer
Fig. 7.30 shows multidimensionality of these
walls
09/21/2010
Biochem: Carbo III, Lipids I
p. 8 of 50
Peptide component
(G&G fig. 7.29)



Sugars are crosslinked with entities
containing
(L-ala)-(isoglutamate)-(L-Lys)-(D-ala)
Gram-neg: L-Lys crosslinks via D-ala
Gram-pos: L-lys crosslinks via
pentaglycine followed by D-ala
09/21/2010
Biochem: Carbo III, Lipids I
p. 9 of 50
Gram-negative bacteria:
the periplasmic space
(G&G fig. 7.30b, 7.31)



Periplasmic space: space inside cell membrane
but inside just-described peptidoglycan layer
(note error in fig. legend!)
Peptidoglycan is attached to outer membrane
via 57-residue hydrophobic proteins
Outer membrane has a set of
lipopolysaccharides attached to it; these sway
outward from the membrane
09/21/2010
Biochem: Carbo III, Lipids I
p. 10 of 50
Gram-negative membranes
and periplasmic space
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
Figure courtesy
Kenyon College
microbiology
Wiki
09/21/2010
Biochem: Carbo III, Lipids I
p. 11 of 50
Glycoproteins





1-30 carbohydrate moieties per protein
Proteins can be enzymes, hormones,
structural proteins, transport proteins
Microheterogeneity:
same protein, different sugar
combinations
Eight sugars common in eukaryotes
PTM glycosylation much more common
in eukaryotes than prokaryotes
09/21/2010
Biochem: Carbo III, Lipids I
p. 12 of 50
Diversity in glycoproteins





Variety of sugar monomers
 or  glycosidic linkages
Linkages always at C-1 on one sugar but
can be C-2,3,4,6 on the other one
Up to 4 branches
But:
not all the specific glycosyltransferases
you would need to get all this diversity
exist in any one organism
09/21/2010
Biochem: Carbo III, Lipids I
p. 13 of 50
O-linked and Nlinked
oligosaccharides

Characteristic
sugar moieties
and attachment
chemistries
09/21/2010
Biochem: Carbo III, Lipids I
p. 14 of 50
O-linked oligosaccharides
(fig. fig 7.32a, 7.33 in G&G)




GalNAc to ser or thr;
often with Gal or Sialic acid on GalNAc
5-hydroxylysines on collagen are joined
to D-Gal
Some proteoglycans joined via
Gal-Gal-Xyl-ser
Single GlcNAc on ser or thr
09/21/2010
Biochem: Carbo III, Lipids I
p. 15 of 50
N-linked
oligosaccharides
(fig. 7.32b,c in G&G)


Generally linked to Asn
Types:



High-mannose
Complex
(Sialic acid, …)
Hybrid
(Gal, GalNAc, Man)
09/21/2010
Biochem: Carbo III, Lipids I
Diagram courtesy
Oregon State U.
p. 16 of 50
iClicker question 1






Suppose you isolate a polysaccharide
with 5000 glucose units, and 3% of the
linkages are 1,6 crosslinks. This is:
(a) amylose
(b) amylopectin
(c) glycogen
(d) chitin
(e) none of the above.
09/21/2010
Biochem: Carbo III, Lipids I
p. 17 of 50
iClicker question 2

Suppose you isolate an enzyme that
breaks down -1,4-glycosidic linkages
between GlcNAc units. This would act
upon:

(a) glycogen
(b) cellulose
(c) chitin
(d) all of the above
(e) none of the above.




09/21/2010
Biochem: Carbo III, Lipids I
p. 18 of 50
Lipids



Hydrophobic biomolecules;
most have at least one hydrophilic
moiety as well
Attend to “periodic table of lipids”
(next slide)
Functions




Membrane components
Energy-storage molecules
Structural roles
Hormonal and signaling roles
09/21/2010
Biochem: Carbo III, Lipids I
p. 19 of 50
Periodic table of lipids
09/21/2010
Biochem: Carbo III, Lipids I
p. 20 of 50
Fatty acids





Unbranched hydrocarbons with carboxylate moieties
at one end
Usually (but not always) even # of C’s
Zero or more unsaturations: generally cis
Unsaturations rarely conjugated (why?)
Resting concentrations low because they could
disrupt membranes
saturated
unsaturated
09/21/2010
Biochem: Carbo III, Lipids I
p. 21 of 50
Trans fatty acids



Not completely absent in biology
But enzymatic mechanisms for
breakdown of cis fatty acids are much
more fully developed
Trans fatty acids in foods derived from
(cis-trans) isomerization that occurs
during hydrogenation, which is
performed to solidify plant-based
triglycerides
09/21/2010
Biochem: Carbo III, Lipids I
p. 22 of 50
Fatty acids:
melting points and structures




Longer chain  higher MP
because longer ones align readily
More unsaturations  lower MP
Saturated fatty acids are entirely flexible;
tend to be extended around other lipids
Unsaturations introduce inflexibilities and kinks
09/21/2010
Biochem: Carbo III, Lipids I
p. 23 of 50
Sources for fatty acids

Bacterial lipids
• Mostly C12-C18
•  1 unsaturation

Plant lipids


High concentration of
unsaturated f.a.s
Includes longer
chains
09/21/2010

Animal lipds


Biochem: Carbo III, Lipids I
Somewhat higher
concentrations of
saturated f.a.’s
Unsaturations four
carbons from methyl
group (omega f.a.)
common in fish oils
p. 24 of 50
Triglyceride composition by
source
Beef
Soybean
Other
Palmitic
Linoleic
Stearic
Other
Palmitic
Oleic
Oleic
Linoleic
Stearic

Courtesy Charles Ophardt,
Elmhurst College
09/21/2010
Biochem: Carbo III, Lipids I
p. 25 of 50
Nomenclature for fatty acids


IUPAC names: hexadecanoic acid, etc.
Trivial names from sources (Table 8.1)







Laurate (dodecanoate)
Myristate (tetradecanoate)
Palmitate (hexadecanoate)
Palmitoleate (cis-9-hexadecenoate)
Oleate (cis-9-octadecenoate)
Linoleate (cis,cis-9,12-octadecadienoate)
Arachidonate
(all cis-5,8,11,14-eicosatetraeneoate)
09/21/2010
Biochem: Carbo III, Lipids I
p. 26 of 50
Saturated Fatty Acids
90
Melting points for saturated FAs
85
80
Melting point, Deg C
75
70
Contrast with
melting points of
Unsaturated C18 FAs:
16ºC, -5ºC -11ºC;
C20, 4 double bonds:
-50ºC
65
60
55
50
45
40
8
12
16
20
24
28
# of Carbons
09/21/2010
Biochem: Carbo III, Lipids I
p. 27 of 50
How fatty acids really appear





Almost always esterified or otherwise
derivatized
Most common esterification is to
glycerol
Note that glycerol is achiral but its
derivatives are often chiral
Triacylglycerols; all three OHs on
glycerol are esterified to fatty acids
Phospholipids: 3-OH esterified to
phosphate or a phosphate derivative
09/21/2010
Biochem: Carbo III, Lipids I
glycerol
p. 28 of 50
Triacylglycerols






Neutral lipids
R1,2,3 all aliphatic
Mixture of saturated &
unsaturated; unsaturated
more than half
Energy-storage molecules
Yield >2x energy/gram as
proteins or carbohydrates,
independent of the waterstorage issue …
Lipids are stored anhydrously;
carbohydrates & proteins aren’t
09/21/2010
Biochem: Carbo III, Lipids I
p. 29 of 50
Catabolism of triacylglycerol



Lipases break these molecules
down by hydrolyzing the 3-O esters
and 1-O esters
Occurs in presence of bile salts
(amphipathic derivatives of
cholesterol)
These are stored in fat droplets
within cells, including specialized
cells called adipocytes
09/21/2010
Biochem: Carbo III, Lipids I
p. 30 of 50
Glycerophospholipids




Also called phosphoglycerides
Primary lipid constituents of
membranes in most organisms
Simplest: phosphatides
(3’phosphoesters)
Of greater significance: compounds in
which phosphate is esterified both to
glycerol and to something else with an
—OH group on it
09/21/2010
Biochem: Carbo III, Lipids I
p. 31 of 50
Categories of
glycerophospholipids




Generally categorized first
by the polar “head” group;
secondarily by fatty acyl
chains
Usually C-1 fatty acid is
saturated
C-2 fatty acid is unsaturated
Think about structural
consequences!
09/21/2010
Biochem: Carbo III, Lipids I
p. 32 of 50
Varieties of head
groups






Variation on other phosphoester
position
Ethanolamine (R1-4 = H) (—O—
(CH2)2—NH3+)
Serine (R4 = COO-)
(—O—CH2-CH-(COO-)—NH3+)
Methyl, dimethylethanolamine
(—O—(CH2)2—NHm+(CH3)2-m)
Choline (R4=H, R1-3=CH3) (—O—
(CH2)2—N(CH3)3+)
Glucose, glycerol . . .
09/21/2010
Biochem: Carbo III, Lipids I
p. 33 of 50
Phospholipids aren’t
interchangeable!



Phosphatidylcholine and
phosphatidylethanolamine are the major
components of eukaryotic membranes
Phosphatidylserine and P-inositol tend to be on
the inner leaflet only, and are more prevalent in
brain tissue than other tissues
Good reference: http://lipidlibrary.aocs.org/
09/21/2010
Biochem: Carbo III, Lipids I
p. 34 of 50
Chirality in common lipids



Fatty acyl chains themselves are
generally achiral
Glycerol C2 is often chiral (unless C1 and
C3 fatty acyl chains are identical)
Phospholipid polar groups are achiral
except for phosphatidylserine and a few
others
09/21/2010
Biochem: Carbo III, Lipids I
p. 35 of 50
iClicker quiz question 3

What is the most common fatty acid in
soybean triglycerides?





(a) Hexadecanoate
(b) Octadecanoate
(c) cis,cis-9,12-octadecadienoate
(d) all cis-5,8,11,14-eicosatetraeneoate
(e) None of the above
09/21/2010
Biochem: Carbo III, Lipids I
p. 36 of 50
iClicker quiz, question 4

Which set of fatty acids would you
expect to melt on your breakfast table?





(a) fatty acids derived from soybeans
(b) fatty acids derived from olives
(c) fatty acids derived from beef fat
(d) fatty acids derived from bacteria
(e) either (c) or (d)
09/21/2010
Biochem: Carbo III, Lipids I
p. 37 of 50
iClicker quiz question 5

Suppose we constructed an artificial lipid
bilayer of dipalmitoyl phosphatidylcholine
(DPPC) and another artificial lipid bilayer
of dioleyl phosphatidylcholine (DOPC).
Which bilayer would be thicker?




(a) the DPPC bilayer
(b) the DOPC bilayer
(c) neither; they would have the same
thickness
(d) DOPC and DPPC will not produce stable
bilayers
09/21/2010
Biochem: Carbo III, Lipids I
p. 38 of 50
Plasmalogens





Ether phospholipids have an ether link to C1 instead
of an ester linking
Plasmalogens are ether phospholipids with C1
linked via cis-vinyl ether linkage.
They constitute the other major category of
phospholipids besides esterified
glycerophospholipids
Ordinary fatty acyl esterification at C2…
platelet activating factor has R2 = CH3
Usually PE or PC at C3 position
09/21/2010
Biochem: Carbo III, Lipids I
p. 39 of 50
Specific
plasmalogens
09/21/2010
Biochem: Carbo III, Lipids I
p. 40 of 50
Roles of phospholipids


Most important is in membranes that
surround and actively isolate cells
and organelles
Other phospholipids are secreted and
are found as extracellular surfactants
(detergents) in places where they’re
needed, e.g. the surface of the lung
09/21/2010
Biochem: Carbo III, Lipids I
p. 41 of 50
Sphingolipids




Second-most abundant membrane
lipids in eukaryotes
Absent in most bacteria
Backbone is sphingosine:
unbranched C18 alcohol
More hydrophobic than phospholipids
09/21/2010
Biochem: Carbo III, Lipids I
p. 42 of 50
Varieties of
sphingolipids

Ceramides



Sphingomyelin
Image on
steve.gb.com
sphingosine at glycerol
C3
Fatty acid linked via
amide
at glycerol C2
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
Sphingomyelins


C2 and C3 as in
ceramides
C1 has phosphocholine
09/21/2010
Biochem: Carbo III, Lipids I
p. 43 of 50
Cerebrosides


Ceramides with one
saccharide unit
attached by glycosidic linkage at
C1 of glycerol
Galactocerebrosides
common in nervous
tissue
09/21/2010
Biochem: Carbo III, Lipids I
p. 44 of 50
Gangliosides


Anionic derivs of cerebrosides (NeuNAc)
Provide surface markers for cell recognition
and cell-cell communication
09/21/2010
Biochem: Carbo III, Lipids I
p. 45 of 50
Isoprenoids




Huge percentage of non-fatty-acid-based
lipids are built up from isoprene units
Biosynthesis in 5 or 15 carbon building
blocks reflects this
Steroids, vitamins, terpenes
Involved in membrane function, signaling,
feedback mechanisms, structural roles
09/21/2010
Biochem: Carbo III, Lipids I
p. 46 of 50
Isoprene units: how they’re
employed in real molecules


Can be linked head-to-tail
… or tail-to-tail (fig. 8.16, G&G)
09/21/2010
Biochem: Carbo III, Lipids I
p. 47 of 50
Steroids



Molecules built up from ~30-carbon four-ring
isoprenoid starting structure
Generally highly hydrophobic (1-3 polar
groups in a large hydrocarbon); but can be
derivatized into emulsifying forms
Cholesterol is basis for many of the others,
both conceptually and synthetically
Cholesterol:
Yes, you need
to memorize
this structure!
09/21/2010
Biochem: Carbo III, Lipids I
p. 48 of 50
Other lipids

Waxes



nonpolar esters of long-chain fatty acids
and long-chain monohydroxylic alcohols,
e.g H3C(CH2)nCOO(CH2)mCH3
Waterproof, high-melting-point lipids
Eicosanoids



QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
oxygenated derivatives of C20
polyunsaturated fatty acids
Involved in signaling, response to
stressors
Non-membrane isoprenoids:
vitamins, hormones, terpenes
09/21/2010
Biochem: Carbo III, Lipids I
Image
courtesy
cyberlipid.
org
QuickTime™
TIFF (Uncompressed)
d
Image
are needed to see th
Courtesy
Oregon
State Hort.
& Crop
Sci.
p. 49 of 50
Example
of a wax

Oleoyl
alcohol
esterified to
stearate
(G&G, fig.
8.15)
09/21/2010
Biochem: Carbo III, Lipids I
p. 50 of 50