Carbohydrates III; Lipids I

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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Biochem: Carbo III, Lipids I p. 2 of 50

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



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



Image courtesy cyberlipid.org


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)

Carbohydrates III; Lipids I

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