09/18/08 Biochemistry: Carbo2/Lipid1 Carbohydrate s II; Lipids I Andy Howard Introductory Biochemistry 18 September 2008
Dec 20, 2015
09/18/08Biochemistry: Carbo2/Lipid1
Carbohydrates II; Lipids I
Andy HowardIntroductory Biochemistry
18 September 2008
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What we’ll discuss
Carbohydrates (concluded): Structural
polysaccharides Glycoconjugates
Proteoglycans Peptidoglycans Glycoproteins
Lipids Characteristics Fatty acids Phospholipids
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Structural polysaccharides I Insoluble compounds designed to
provide strength and rigidity Cellulose: glucose -14 linkages
Rigid, flat structure: each glucose is upside down relative to its nearest neighbors (fig.7.27)
300-15000 glucose units Found in plant cell walls Resistant to most glucosidases Cellulases found in termites,
ruminant gut bacteria Chitin: GlcNAc -14 linkages:
exoskeletons, cell walls (fig. 7.29)
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Structural polysaccharides II Alginates: poly(-D-mannuronate),
poly(-L-guluronate), linked 14 Cellulose-like structure when free Complexed to metal ions:
3-fold helix (“egg-carton”) Agarose: alternating D-gal, 3,6-anhydro-L-gal,
with 6-methyl-D-gal side chains Forms gels that hold huge amounts of H2O Can be processed to use in the lab for gel exclusion
chromatography Glycosaminoglycans: see next section
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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.
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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.
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Glycoconjugates Poly or oligosaccharides
covalently linkedto proteins or peptides
Generally heteroglycans Categories:
Proteoglycans (protein+glycosaminoglycans)
Peptidoglycans (peptide+polysaccharide) Glycoproteins (protein+oligosaccharide)
Image courtesy Benzon Symposia
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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
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Proteoglycans in cartilage Highly hydrated,
voluminous Mesh structure
(fig.7.47 or this fig. from Mathews & Van Holde)
Aggrecan is major proteoglycan
Typical of proteoglycans in that it’s extracellular
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Peptidoglycans
Polysaccharides linked to small proteins Featured in bacterial cell walls:
alternating GlcNAc + MurNAclinked with -(14) linkages
Lysozyme hydrolyzes these polysaccharides Peptide is species-specific: often contains D-
amino acids
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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. 7.36 shows multidimensionality of these
walls
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Peptide component (fig. 7.34) 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
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Gram-negative bacteria:the periplasmic space (fig. 7.37)
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
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Gram-negative membranes and periplasmic space
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
Figure courtesy Kenyon College microbiology Wiki
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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
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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
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O-linked and N-linked oligosaccharides
Characteristic sugar moieties and attachment chemistries
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O-linked oligosaccharides(fig. 8.34)
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 viaGal-Gal-Xyl-Ser
Single GlcNac on ser or thr
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N-linked oligosaccharides
Generally linked to Asn Types:
High-mannose Complex
(Sialic acid, …) Hybrid
(Gal, GalNAc, Man)
Diagram courtesy Oregon State U.
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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
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Periodic table of lipids
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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
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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
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Fatty acids:melting points and structures
Longer chain higher MPbecause 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
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Sources for fatty acids Bacterial lipids
• Mostly C12-C18
• 1 unsaturation Plant lipids
High concentration of unsaturated f.a.s
Includes longer chains
Animal lipds Somewhat higher
concentrations of saturated f.a.’s
Unsaturations four carbons from methyl group (omega f.a.) common in fish oils
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Triglyceride composition by source
Courtesy Charles Ophardt, Elmhurst College
Beef
Linoleic
Other
Oleic
Stearic
Palmitic
Soybean
Palmitic
Stearic
Oleic
Linoleic
Other
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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)
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Saturated Fatty AcidsMelting points for saturated FAs
40
45
50
55
60
65
70
75
80
85
90
8 12 16 20 24 28
# of Carbons
Melting point, Deg C
Contrast withmelting points ofUnsaturated C18 FAs:16ºC, -5ºC -11ºC;C20, 4 double bonds: -50ºC
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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
glycerol
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Triacylglycerols Neutral lipids R1,2,3 all aliphatic Mixture of saturated &
unsaturated; unsaturatedmore than half
Energy-storage molecules Yield >2x energy/gram as
proteins or carbohydrates, independent of the water-storage issue …
Lipids are stored anhydrously; carbohydrates & proteins aren’t
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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
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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
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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!
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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 . . .
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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