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Introduction to the macromolecules of lifeand cell structures. Introduction to lipids andcell membranes. Barrier role and structure ofmembranes. Organelle structure, roles oforganelles, role of compartmentalisation,comparison between plant and animal cells. [HB]
BIOLOGICAL CHEMISTRYProf. J.H.P. Bayley, Dr. R.M. Adlington and Dr. L. Smith
Trinity Term 2007 - First Year
Lecture 2Hagan Bayley
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RECOMMENDED TEXTBOOK
“Biochemistry” 5th edition 2002JM Berg, JL Tymoczko, L Stryer
Freeman
We call this book “Stryer”This week mainly Chapter 12
Figures mainly from Bruce Alberts et al.“Molecular Biology of the Cell”Also a good text for organelles
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Lecture notes are at:
www.chem.ox.ac.uk/bayleygroup/
on weblearn soon
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Introduction to lipids and cell membranesFUNCTIONS OF MEMBRANES
Boundary of cells and organellesconcentrate enzymes, metabolites etc.ionic gradientsreducing environmentpH controletc- i.e. membranes maintain the intracellular environment
Import and export- proteinstransporterssecretion
Electrical signals- also proteinschannels
Organization of enzymes and cytoskeleton
Energy storage and utilization
Signaling
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MEMBRANE COMPOSITION
Lipids
Proteinschannelspumpsreceptorsenzymes
Oligosaccharides (attached to lipids or proteins)
Lipid: protein ratiomyelin 3: 1plasma membrane 1: 1mitochondrial inner membrane 1: 3
about 30% ofproteinsencoded in thegenome aremembraneproteins
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LIPIDS
3 major classesphospholipidsglycolipidscholesterol
amphipathic molecules
about 109 lipid molecules in a small eukaryotic cell
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Four representations of a phosphatidylcholine moleculethe kink in the unsaturated fatty acid chain is exaggerated
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The four major phospholipids of mammalian membranesfatty acids 14- 24 carbon atoms16 carbon and 18 carbon predominatesaturated and unsaturated
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Glycolipid molecules
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Various representations of cholesterol
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The lipids in archaea are distinctive
Ether links- will not hydrolyzeSaturated fatty acid chains- will not be oxidized
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Wedge-shaped lipid molecules tend to form micelles, whilecylinder-shaped phospholipids form bilayers
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Driving forces for bilayer formation
Hydrophobic effect- buried side chains
Van der Waals interactions between side chains
Headgroups interact with water- electrostatics andhydrogen bonding
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Electron microscopy of a pure lipid bilayer (liposome)
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PERMEABILITY COEFFICIENT
typical values for PS:
Na+ 10-12 cm s-1
tryptophan 10-7 cm s-1
water 5 X 10-3 cm s-1
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LIPID DIFFUSION
For a one-dimensional random walk:
xrms = (2Dt)1/2
x = mean distance from a point in time t
t = x2/ 2D
lipids D = 10-8 cm2 s-1 = 1 µm2 s-1
For 1 µm, t = 0.5 sand for 10 µm = 50 s
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LIPID FLIP-FLOP
Flip-flop by contrast with diffusion confined to one leaflet is veryslow:
1 per month per phospholipid
This is the basis of lipid asymmetrysphingomyelin/ phosphatidylcholine outsidephosphatidylethanolamine/ phosphatidylserine insidecholesterol in both halves
These distributions, set up during biosynthesis, cannot changeunless catalyzed
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Glycolipids
part of cell coat-glycocalyx
cell-cell recognition
toxin receptors
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PROTEINS in membranes
Fluid mosaic model
Various topographiesIntegral- cannot be extracted except with detergentsMostly membrane spanning
Peripheral- extractable with salt or base (e.g.proteins of the cytoskeleton)
Proteins with lipid anchors- e.g. myristoyl, prenyl-most of these act like integral proteins
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PROTEINS continued
No flip-flop
Single orientation arising from biosynthesis inendoplasmic reticulum (ER)
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… the first major class ofmembrane protein is theα helix bundle …
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porin: 16-stranded β barrel
… the second majorclass is the β barrel …
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Prostaglandin synthaseCatalyzes the conversion of arachidonic acid to prostaglandin PGG2 and then to PGH2
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Cytoskeleton- example of peripheral membrane proteins
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Electron microscopy of red cell cytoskeleton
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Summary of membrane properties
Thin sheet-like structures based on the lipid bilayer
Contain proteins that provide function
Non-covalent assemblies
Asymmetric
Fluid
Transmembrane potential
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COMPARTMENTALIZATION
Boundary of cells and organellesconcentrate enzymes, metabolites etc.ionic gradientsreducing environmentpH controletc- i.e. membranes maintain the intracellular environment
Import and exporttransporterssecretion
Electrical signalspumps and channels
Organization of enzymes and cytoskeleton
Energy storage and utilization
Signaling
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Focus on organelles
Introduction to the macromolecules of lifeand cell structures. Introduction to lipids andcell membranes. Barrier role and structure ofmembranes. Organelle structure, roles oforganelles, role of compartmentalisation,comparison between plant and animal cells.
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The major organelles of a eukaryotic cellare:NUCLEUS – contains the chromosomes, which consist of DNAand histones. Gene replication. mRNA synthesis. Ribosomeproduction.
MITOCHONDRIA – principal function is the production of ATP
ENDOPLASMIC RETICULUM:ROUGH – studded with ribosomes- sites of protein synthesis formembrane and secreted proteinsSMOOTH –steroid hormone biosynthesis, Ca2+ storage
LYSOSOMES - contain hydrolytic enzymesPEROXISOMES - contain oxidative enzymesThe lysosomes and peroxisomes degrade foreign substances thathave been brought into the cell (simplification)
GOLGI COMPLEXES –newly biosynthesised proteins areprocessed here (post-translational modification), e.g. glycosylated
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Plant cells: plastids (e.g. chloroplast-photosynthesis), vacuoles (control hydrostaticpressure through fluid uptake, storage andbreakdown of molecules), cell wall
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Bacterial membranes
Escherichia coli
Staphylococcus aureus
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Major organelles- membrane structure and originMitochondrion- Double membrane cf certain bacteria. Endosymbiosis: own DNA andinternal ribosomes; replicate but only semiautonomous (cannot exist outside the eukaryotic cell)
Nucleus- Double membrane through which nuclear pores penetrate, directly connected to therough endoplasmic reticulum (ER)
Endoplasmic reticulum- Single membrane. Rough ER is site of secreted andmembrane protein synthesis on external membrane-bound ribosomes
Golgi- Single membrane. No DNA or internal ribosomes
Endosomes- Single membrane. No DNA or internal ribosomes
Lysosomes- Single membrane. No DNA or internal ribosomes
Peroxisomes- Single membrane. Thought to divide by enlargement and division, but recentresults suggest peroxisomes are derived from the ER: Cell 122, 85-95 (2005); Current Biology 15,R774-R776 (2005). No DNA or internal ribosomes
Plants (cell wall)Vacuole- Single membrane. No DNA or internal ribosomes
Chloroplast- Double membrane cf certain bacteria. Contains pinched off stackedmembranes- thylakoids. Endosymbiosis: own DNA and internal ribosomes; replicates but onlysemiautonomous (cannot exist outside the plant cell)
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Origin of organelles other than mitochondria
nucleus
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Endosomes: import into cells (good e.g. lipoproteins, bad e.g. some viruses,toxins)
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Mitochondria (singular: mitochondrion)Mitochondria generate ATP- the energy “currency” of thecell. They are semiautonomous. They encode some butnot all of their own proteins. They have exchangedgenes with the nucleus-- in turn the host cell nowrequires their ATP.
Glycolysis (anaerobic, in the cytoplasm) generates someATP and also pyruvate.
In the mitochondrion:• pyruvate acetylCoA• In the Krebs cycle: acetate 2CO2/ GTP/ 8e- (asFADH2 and NADH)• Used to generate a proton gradient across the innermitochondrial membrane- (8e- / 2O2 36 H+
translocated)• Proton gradient converts ADP + Pi ATP, using ATPsynthase- 3 H+ translocated per ATP?
???Why does this require compartmentalization?
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mitochondrion
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mitochondrial inner membrane
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ATP synthaseForms ATP from ADP and Pi by using a transmembrane proton gradient as an energysource
see you in Week 4