(EN)Lecture 17 - Lipids I - 國立交通大學開放式課...
Transcript of (EN)Lecture 17 - Lipids I - 國立交通大學開放式課...
國立交通大學生物科技學系蘭宜錚老師 1
Lecture 17Lipids• Understand and familiarize the nomenclature of fatty acids• Understand the structure of lipids and their characteristics
• Understand how lipids make membranes• Membrane associated protein / transmembrane proteins• Molecular transport across membrane occurs via several mechanisms
DBT2117: Biochemistry (I)
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• Lipids are a broad group of molecules with the characteristics of having longhydrophobic carbon chains
• Lipid molecules are commonly found in fats, oils, waxes, certain vitamins (A, D,E, etc), soaps (detergents), etc…
• Most significant function of lipids for biology is the formation of membranes
Occurrence of lipids in biology
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• Lipid monomer in general contain both ahydrophilic head and a hydrophobic tail
• Typically a lipid molecule is insoluble in water(due to the long hydrophobic tail).
• HOWEVER! Lipids associate with eachother and form water soluble structuresby displaying hydrophilic head on theoutside (in aqueous solution)
• These structures include:• Micelles• Vesicles• Bilayers
• Note: when lipids are used to make energystorage, they are turned into insoluble oils.
Polar or charged functional groups
Nonpolar carbonChain(s)
The Molecular Structure and Behavior of Lipids
• Hydrophobic compounds aggregates in aqueous solution and exclude water out.
• Recall that this phenomenon is due to maximizing water entropy
http://photographyblogger.net/18‐interesting‐pictures‐of‐oil‐in‐water/
Hydrophobic effect
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• Micelles:
• Vesicles
• Bilayers (cell membrane)
Basically almost the same asvesicles…
Na+
Na+
Na+
Na+
Na+
Na+ Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+Na+ Na+ Na+ Na+
2 layers:Outside aqueous (water)Inside organic (oil)
3 layers:Outside aqueous (water)Middle layer organic (oil)Inside aqueous (water)
Structures of water soluble lipids
• Fatty acids can make up other more complex lipids such as triacylglycerides
• Fatty acids are long carbon chain carboxylic acids typically with even number carbons
• Can be either• Saturated – only (C‐C) Carbon SINGLE bonds through out chain• Unsaturated – contains (C=C) Carbon DOUBLE bonds (one or more)
• In nature, unsaturated fatty acids are mainly cis‐fatty acids• Trans‐fatty acids are synthetically produced as a side contaminating product of food
industry. Consumption of these fatty acids increases risk to heart diseases.
Simplest lipid monomer: Fatty acids
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• Humans can make saturated fatty acids and most other fatty acids needed by our body bymetabolizing carbohydrates and proteins (sources of carbon, hydrogen, and oxygen)
• However! We cannot synthesize omega‐3 and omega‐6 unsaturated fatty acids
• We need omega‐3 and omega‐6 to synthesize hormone‐like molecules called eicosanoids.Eicosanoids help regulate blood clotting, blood pressure, immune function, and other bodyprocesses
E. Generalic, http://glossary.periodni.com/glossary.php?en=fatty+acid
ω‐3
ω‐6
ω‐9
Unsaturated fatty acids – essential diet for humans
Distribution of fatty acids in common cooking oil
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• X:Y (c/t) Δn,n,n• 18:3c Δ9,12,15 • 18 carbons in total length
• 3 unsaturated bonds• c for cis‐unsaturation• 9,12,15 are position of the C=C double
bonds
How to represent fatty acids
• Triacylglyceride (also known as: triacylglycerol, triglyceride, TAG) is an ester ofglycerol + 3 fatty acids
• Note that the original hydrophilic head is gone afterbonding with glycerol
• TAG is water insoluble• TAG form oil droplets inside of cells (adipocytes)
of adipose tissues
Just as with sugars, in order for this reaction to occur… glycerol & fatty acid have to be “activated”
We will talk more about this when we talk about lipid biosynthesis
Covalently bonded fatty acids: triacylglycerides
glycerol
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1. Energy production ‐most fat in most animals is oxidized for the generation ofATP, to drive metabolic processes.
2. Heat production ‐ specialized cells (in “brown fat” of warm‐blooded animals, forexample) oxidize triacylglycerols for heat production, rather than to make ATP.
3. Insulation ‐ in animals that live in a cold environment, layers of fat cells underthe skin serve as thermal insulation. The blubber of whales is one obviousexample.
Functions of fat storage in animals
• Consider animal fat and vegetable oil…
• Both are triacylglycerides, how come animal fat is solid at room temperaturewhile vegetable oil is liquid?
VS.
• Answer is in the saturation of the fattyacid that make up the fat/oil
• Unsaturated fatty acids increases thefluidity of the TAG• This property is due to the “kinks”
that C=C bond causes in packing.Presence of C=C causes them topack less well…
Not all triacylglycerides are the same
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• Soap is fatty acid salt.
• When fats are hydrolyzed with strong bases such as NaOH or KOH (in earlier times, wood ashes were used), a soap is produced.
• This process is called saponification.
• The fatty acids are released as either sodium or potassium salts, which are fullyionized.
• However, as cleansers, soaps have the disadvantage that the fatty acids are precipitated bythe calcium or magnesium ions present in “hard” water, forming a scum and destroying theemulsifying action.
• To circumvent that, synthetic detergents are developed.• A classical example is SDS (Sodium dodecyl Sulfate), a common detergent used in
biochemical research for analyzing proteins.
Soaps and detergents
http://www.madehow.com/Volume‐2/Soap.html
Small companies: batch production
Large companies: continuous production
How soaps are made
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• Wax is an ester formed by fatty acid and fatty alcohol
• Wax occurs naturally in plants & fruits
• Wax is generally completely water insoluble
• As with the triacylglycerols, the firmness of waxes increases withchain length and degree of hydrocarbon saturation.
Waxes
• In most case, lipid molecules that make up the membrane contains:• One highly polar head group• TWO hydrophobic tails
• 2 hydrophobic tails are typically observed and makes sense because of its shape…
Biological membranes
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• Four major classes of membrane‐forming lipids:
• Glycerophospholipids• Glycerol as backbone + phosphate‐containing head group
• Glycoglycerolipids• Sugar containing glycerolipids
• Sphingolipids• Sphingosine based
• Glycosphingolipids• Sugar containing sphingo based lipid
• Cholestrols are also commonly found in animal membranes
Biological membranes
Composition of some biological membranes
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• Glycerol is a prochiralmolecule.
• Phosphorylation of one CH2OH group or the other gives the R‐ or S‐enantiomer ofglycerol phosphate.
• The same molecule can be called L‐glycerol‐3‐phosphate or D‐glycerol‐1‐phosphatedepending on the carbon numbering scheme.
Same thing can have two names…
Stereochemistry of glycerophospholipids
• It is necessary to standardize number assignment
• Therefore, the current adapted convention is the sn (stereochemical numbering) system.
Standardize nomenclature – sn convention
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• R1, R2, R3 refers to groups attached at C1, C2,C3 position, respectively
• R1 and R2 are generally bonded to fatty acylgroups – forms the hydrophobic part
• R1 & R2 can vary in• carbon chain length• saturation
• In phospholipids, R3 contains a phosphate or itsderivative, which makes the hydrophilic part.
• R3 can vary in• different phosphate derivatives
Glycerophospholipid
• Glycoglycerolipids are less frequent in animal membranes
• They are widespread in plant (especially chloroplast) and in various microbes
• Glycoglycerolipids have sugar at R3
• Example shown above is monogalactosyl diglyceride, which accounts for abouthalf lipid in chloroplast membrane
Glycoglycerolipids
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• Sphingolipids is built on amino alcohol sphingosine (rather than glycerol)
• Sphingosine:• naturally has a hydrophobic tail of 15 carbons• C=C at the beginning of its hydrophobic tail• Contains a primary amine ( ‐NH2) at C2• Contains a primary hydroxyl (‐OH) at C1• Contains a secondary hydroxyl (‐OH) at C3
• Because sphingosine already has one tail, it just needs another fatty acid to form the basicmembrane lipid.
• Ceramide ‐ Fatty acid attach to C2 via amide bond.
• Sphingomyelin – further modification of ceramide at C1 with phosphocholine
1
2
3
Sphingosine
Ceramide
Sphingomyelin
Sphingolipids
• Glycosphingolipids are ceramides + sugars at C1
• Cerebrosides – one sugar attached• Typically glucose or galactose
• Gangliosides – one or more sialic acid attached• Different gangliosides differ in position and
number of sialic acid
• These molecules are especially common inmembranes of nerve cells
Glycosphingolipids
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http://en.wikipedia.org/wiki/Cerebroside
Structural comparison between sphingolidpids
• Cholesterol, is a component of many animal membranes.
• It influences membrane fluidity by its bulky structure
Chair form for the rings – rigid structure
When present in membrane, will disrupt hydrophobic tail packing
Cholesterol Membrane fluidity
Cholesterol
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• Cholesterol is precursor to many hormones
(Male sex hormone)
(immunosuppressant)
(Female sex hormone)
(regulate blood pressure)
(immunosuppressant) (immunosuppressant)
Cholesterol
• Fluid mosaic model proposed by S. J. Singer and G. L. Nicolson in 1972.
• A membrane is a fluid mixture of lipids and proteins.
• Peripheral membrane proteins are associated with one side of the bilayer and can be separated from the membrane without disrupting the bilayer. May or may not be attached to the membrane.
• Integral membrane proteins are more deeply embedded in the bilayer and can only be extracted under conditions that disrupt membrane structure.
• Many integral membrane proteins extend through the bilayer.
http://en.citizendium.org/wiki/Cell_membrane
Membranes are dynamic fluids
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• Membrane proteins and membrane components areconstantlymoving around redistributing themselves.
• They move in 2D (lateral diffusion)
Membrane components move around
• Component of the membrane
• Length of the hydrophobic tail• Unsaturation of the hydrophobic tail• Amount of cholesterol
• Temperature• Cold = stiff• Hot = fluidly
• Transition temperature ofmembrane:
• Temperature whichmembrane go fromGel to semifluid liquidcrystalline
• Biological membrane atphysiological condition is atsemi‐fluid liquid crystallinestate
What factors affect membrane properties?
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Composition of common biological membranes
Transverse movements
• “flip‐flop” are more difficult (slower)to occur.
• Typically, this flip‐flop movement isaided by enzymes
Lateral vs. transverse movement
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• The two leaflets of a membrane usuallydiffer in lipid composition.
• Lipid composition in the outer leaflet(green) and inner leaflet (gold) of theplasma membrane is graphed for threecell types.
• PC phosphatidylcholine• PE phosphatidylethanolamine• PS phosphatidylserine• PI = phosphatidylinositol• SP = sphingomyelin
leaflet
Asymmetry of membranes
• Peripheral proteins attach to membrane through association• They are present on one leaflet
Erythrocyte membrane• Contains few proteins on outside of the cell• Contains 2D network of actin, band 4.1, and spectrins, on the inside surface of
cell• The structural network of these proteins provide excellent support for
maintaining its shape
Peripheral protein
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• Integral membrane proteins contains hydrophobic residues that promote association withthe hydrophobic tails of membrane
Integral proteins
α-helices β-barrels
(bacteria rhodopsin) (OmpF porin)
• Transmembrane domains typically form α‐helices or β‐sheets with hydrophobic residues
Typical transmembrane domain structures
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• The sequence and postulated structure of glycophorin A (protein used to carry sugars, inparticular, sialic acid on red blood cells):
• This protein was the first integral membrane protein to be sequenced. The external (N‐terminal) domain carries 15 O‐linked and one N‐linked oligosaccharides; together theseconstitute ~60% of the total protein mass.
o The single transmembrane helix is highly hydrophobic.o The cytosolic C‐terminal domain is quite hydrophilic.
Integral membrane proteins have transmembrane domains
Bacteriorhodopsin‐ an integral membrane protein:
• A key enzyme for photosynthesis in somebacteria (not the same found in plants).
• Functions as a light driven proton pump
• Seven helices span the membrane
Hydrophobic residues
Hydrophobicity plot
Integral membrane proteins have transmembrane domains
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When inserting proteins into the membrane
• Membrane rafts or lipid rafts arerich in cholesterol, sphingolipids, andGPI‐linked proteins.
• The bilayer is thicker in rafts than inthe surrounding membrane.
• The proteins coalesce and formnanometer‐sized dynamic raftdomains, which may be stabilized byinteractions with actin fibers.
• Rafts can associate to form largerstructures (“platforms”).
• Certain proteins interactpreferentially with rafts (orangeshading), while others do not (brownshading) or are excluded.
Membrane rafts