Ch9-120224 - CHEM 350 Introduction to Biological Chemistry...

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Unformatted text preview: CHEM 350: Introduction to Biological Chemistry Brian Lee, Ph.D. [email protected] Office: Neckers 146G or 324 Phone: 453-7186 Hours: 9:30am to 10:30am or by appointment Website: https:/ / Textbook (required, U.S. edition only) Fundamentals of Biochemistry, 3rd Ed., Voet, Voet & Pratt. Study Guide (recommended) Student Companion to Fundamentals of Biochemistry, 3rd Ed. Help Desk Tuesday 6:30 to 7:30 pm in Neckers 218 Thursday 5:00 to 6:00 pm in Neckers 410 Announcements Undergraduate Research Opportunities Research for credit (such as CHEM 396 or CHEM 496) Student worker ($8.00 per hour) ( Undergraduate Assistantships ( McNair Scholars Program ( REACH Awards Competition ( Summer Research Experiences for Undergraduates (REU) Deadline for SIUC REU Program is March 7th For other REU programs, search the National Science Foundation site: Students must contact the individual sites for information and application materials. NSF does not have application materials and does not select student participants. A contact person and contact information is listed for each site. Assignments Read Chapter 9 Lipids and Biological Membranes Chapter 9 Problems Student Companion site for Voet, Voet & Pratt Second Midterm Exam, Wednesday February 29th Chapters 6 through 9 (All exams are cumulative) No class on Monday, February 27th (no office hours) Help Desk Tuesday 6:30 to 7:30 pm in Neckers 218 Thursday 5:00 to 6:00 pm in Neckers 410 Lipids as Hormones: Intercellular Messengers Steroids are carried by the bloodstream to distant tissues to regulate metabolism, inflammation, kidney function, and reproductive development. As oxidized derivatives of sterols, steroids are more polar than cholesterol and bind to receptors on the membrane surface. Steroid drugs have an anti-inflammatory effect by inhibiting phospholipase activity and reducing prostagladin synthesis. Vitamin D production and metabolism Photolytic action of UV light Vitamin D regulates metabolism in kidneys, bones and intestines. Rickets Vitamin D deficiency reduces uptake of Ca2+ from intestines. Vitamin D toxicity Excess vitamin D leads to high Ca2+ seru m levels causing calcification and kidney stones. Steroid synthesis: Sterols and other isoprenoids are synthesized by combining isoprene units. Seven isoprene units are used to make squalene, a precursor for sterol. isoprene (5 carbons) Steroid synthesis: Oxidosqualene cyclase creates the four ring structure of the the sterol precursor. 19 steps are required to generate cholesterol from the rearrangement of lanosterol. Other isoprenoids are built from isoprene units. Hydrophobic tails make vitamins “fat soluble”. Protects against oxidative damage to proteins and lipids. No evidence that supplements of vitamin E are beneficial. Warfarin blocks activation of prothrombin by vitamin K dependendent carboxyglutamase Ubiquinone and Plastoquinone are electron carriers. “Fat soluble” - found within the membranes of mitochondria and chloroplast, necessary for ATP synthesis through oxidative phosphorylation and photophosphorylation. Vitamin A1, precursors and derivatives Retinal is essential for vision (cis to trans). Outside of the eye, retinoic acid acts as a hormone to stimulate tissue repair, but can also be teratogenic (causes birth defects). How do Lipids form Cell Membranes? Micelle to Bicelle Single tail lipids do not co mpletely exclude water in the bicelle structure. Single tail lipids are not useful for the lipid bilayer. Bicelle formed by lipids with two tails Cylindrical form leads to better packing in bilayer portion, but not at the rounded ends. Lipid Bilayer in a liposome maximizes the packing interactions. There are no rounded ends as in the bicelle. Membrane dynamics low temperature: semisolid gel phase high temperature: liquid-disordered state Intermediate temperature: liquid-ordered state Cellular activities are optimal in the intermediate liquid-ordered state. Bacteria vary the ratio of unsaturated lipids in the cell membrane depending on temperature of environment. Animals use the rigid cholesterol to decrease membrane fluidity and inhibit interactions between fatty acid chains. This broadens the transition range between flui d and solid. cholesterol unsaturated saturated lower TM high TM Motion of single phospholipids in a bilayer: Flippase maintains correct composition of inner and outer faces of the cell membrane. An untethered lipid moves very rapidly. Same applies to “fat soluble” molecules Measurement of lateral diffusion rates by fluorescent recovery after photobleaching (FRAP). Diffusion is dependent on membrane fluidity which varies with the melting temperature of the lipid components. Higher melting temperatures are indicative of more viscous lipids. Ideal membrane is both flui d-like and solid-like. Fluid mosaic model of membrane structure Figure 9-25 Lipid Rafts - stable associations produce a microdomain Membrane proteins make up 50% of the cell membrane Essential for function of cell membrane: transport, signaling, adhesion, metabolism, photosynthesis, etc. Integral membrane proteins associate with lipids in membrane Hydrophobic interactions – lipid tails Salt-Bridge and Hydrogen Bonding – head groups Polar and charged residues internal Glycosylation – external domain Hydrophobic residues Transmembrane helix 3.6 res/turn 5.4 Å rise/turn 27-35 Å membrane depth 19-25 residues in helix Hydropathy plot shows region of hydrophobic residues Bacteriorhodopsin OmpF porin Cell Adhesion Integral proteins that function in cell-cell interactions and cellextracellular matrix proteins interactions Lipid linked proteins can associate with membrane Prenylation – farnesyl or geranylgeranyl isoprenoids Cysteine thiol linkage C-terminal -C-X-X-Y X – alaiphatic Membrane Associated Proteins – lipid linked or head group Myristoylation – N-terminal Gly residue typically intracellular or organelle proteins Palmitoylation – Cys residue linked to palmitic acid cytoplasmic face of membrane – cell signaling Glycosylphosphatidylinositol-linked protein (GPI anchor) extracellular membrane bound proteins Protein Lipid Protein targeting depends on amino acid sequence and linked lipids and carbohydrates The secretory pathway – directed by the signal peptide. Signal Recognition Particle (SRP) - GTP driven recognition. SRP Receptor on ER membrane, also GTP triggered. Translocon – peptide insertion and TM embedding. The signal peptide at the N-terminus of a protein directs the ribosome to the Rough ER for completion of protein synthesis and insertion into the ER. SecY translocon in prokaryotes forms a hydrophilic pore in the membrane to allow passage of the nascent growing peptide chain into the periplasmic space. Sec61 is eukaryotes performs the same task for transport into the RER. Hydrophilic pore in the middle of SecY Allows hydrophilic nascent peptide to pass through the RER membrane What happens when a hydrophobic stretch of the nascent peptide chain enters the pore? Model fo of a hyd transmem helix or sequence bilayer o Cytoplasmic and mit il proteins are synthesized on free ribosomes. The signal peptide directs the ribosome to the Rough ER. After synthesis and initial processing, proteins are transport from the Rough ER to the Golgi apparatus for final processing. From the Golgi, proteins are transport to the membrane for insertion or secretion, or to the lysosome, or back to the Golgi or ER. Vessicle Fusion Clathrin coated vessicles Clathrin coated vessicles Nerve impulses are transmitted across the synapse between neurons by small molecules. Neurotransmitters are released from vessicles into the synaptic cleft. SNARES mediate vesicle fusion with a membrane. Q-SNARES – glutamine. R-SNARES – arginine. SNARES associate through coiled-coil interaction Tetanus and botulinum neurotoxins target SNARES and prevent vessicle fusion blocking release of neurotransmitters required for signal transmission. Q-SNARES on the target membrane surface include SNAP-25 and syntaxin (green and red). R-SNARE on the vessicle surface is synaptobrevin (blue). SNARE helices are amphipathic. A seven residue repeat sequence: a-b-c-d-e-f-g with a and d residues being hydrophobic. Errata: The textbook mixed up syntaxin and synaptobrevin in the legend to Fig 9-44 ...
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This note was uploaded on 03/26/2012 for the course CHEM 350 taught by Professor Lee during the Spring '08 term at SIU Carbondale.

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