09/21/2010Biochem: Carbo III, Lipids I
Carbohydrates III;Lipids I
Andy HowardIntroductory Biochemistry,
Fall 201021 September 2010
As delivered by Nick Menhart
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Sugar Complexes and Lipids
Sugars form complexes with proteins and lipids
Lipids are critical as energy storage molecules and as components of membranes
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Plans for Today Glycoconjugates Proteoglycans Peptidoglycans Glycoproteins
Lipids Classes of lipids
Fatty acids Triacylglycerols
Lipids, continued Glycero-phospholipids
Plasmalogens Sphingolipids Isoprenoids Steroids Other lipids
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Glycoconjugates Poly or oligosaccharidescovalently 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 isGalN, 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.7.36 or this fig. from Mathews & Van Holde)
Aggrecan is major proteoglycan
Typical of proteoglycans in that it’s extracellular
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Peptidoglycans(G&G fig. 7.29) 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. 7.30 shows multidimensionality of these walls
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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
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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
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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. 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 viaGal-Gal-Xyl-ser
Single GlcNAc on ser or thr
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N-linked oligosaccharides (fig. 7.32b,c in G&G) Generally linked to Asn
Types: High-mannose Complex(Sialic acid, …)
Hybrid(Gal, GalNAc, Man)
Diagram courtesy Oregon State U.
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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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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 Acids
Melting 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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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/
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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
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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
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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)
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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
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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
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Specific plasmalogens
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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
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Sphingolipids Second-most abundant membrane lipids in eukaryotes
Absent in most bacteria Backbone is sphingosine:unbranched C18 alcohol
More hydrophobic than phospholipids
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Varieties of sphingolipids Ceramides
sphingosine at glycerol C3
Fatty acid linked via amideat glycerol C2
Sphingomyelins C2 and C3 as in ceramides
C1 has phosphocholine
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
SphingomyelinImage on steve.gb.com
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Cerebrosides Ceramides with one saccharide unit attached by -glycosidic linkage at C1 of glycerol
Galactocerebrosides common in nervous tissue
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Gangliosides
Anionic derivs of cerebrosides (NeuNAc)
Provide surface markers for cell recognition and cell-cell communication
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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
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Isoprene units: how they’re employed in real molecules
Can be linked head-to-tail … or tail-to-tail (fig. 8.16, G&G)
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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 syntheticallyCholesterol:Yes, you need to memorize this structure!
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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 oxygenated derivatives of C20
polyunsaturated fatty acids Involved in signaling, response to stressors
Non-membrane isoprenoids:vitamins, hormones, terpenes
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
Image courtesy cyberlipid.org
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.Image Courtesy Oregon State Hort. & Crop Sci.
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Example of a wax Oleoyl alcohol esterified to stearate (G&G, fig. 8.15)
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