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Final Exam Notes These are condensed notes for all 22 Lectures. They come directly from the lecture slides and the notes taken in class.

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Mary- Ellen Harper

Lecture 1 April-12-11 10:33 AM Brain requires glucose all the time. Muscle can last on fatty acids very well. RBCs rely on glucose. Type 2: Insulin Resistance Type 1: Autoimmune disease, body attacks insulin releasing cells. - Storage of energy as fat is very efficient. Much higher energy in fat. Carbohydrates require lots of water weight in order to store. - Small ATP free in the body. Lots of ATP is turned over though. Metabolism - the sum of biochemicalprocesses involved in the synthesis, breakdown, and inter- conversion of constituents in cells and organisms Intermediary metabolism - is where anabolism and catabolism intersect, often sharing pathways and metabolites. - Because the pathways of intermediary metabolism are essential for life, they are tightly regulated through a variety of mechanisms. Gene sequencing and Genome databases DNA microarrays: mRNA expression levels and microRNAs - To simultaneouslyassess expression levels of thousands of genes. - To assess the origins and developmentof disease, the subtypes of disease; disease prognosis (e.g., in cancer); treatmentoutcomes - To clarify the specificity of pharmaceuticals Cluster Analysis Many systemsbiology approaches for data analysis. Cluster-type approaches assess levels of transcripts, proteins or metabolitesin relation to known pathways and biological functions. Proteomics:protein expression levels, and post-translational modifications - expression levels and characteristics of proteins - Proteomicapproaches allow investigation into responses of a biological system to different stimuli, e,g, disease states, or following drug treatment - Recent progress in analytical techniques for the study of proteins has led to significant improvementsin the ability to identify peptides and their posttranslational modificationson a high throughput basis One gene one protein hypothesis is wrong Ghrelin/Obestatin do different things but made from one gene Ghrelin signals you are hungry, obestatin signals you are full Metabolomics: comprehensiveanalyses of metabolitelevels Metabolomics: comprehensiveanalyses of metabolitelevels - A new investigativefield that applies advanced analytical techniques to study metabolite profiles in serum or tissue samples. - Several hundreds of metabolitessimultaneously! - By comparing metabolite levels in sequential samples and inferring metaboliteflux, metabolomicscan also identify rate-controlling steps e.g., that could be targeted for the developmentof new drugs. Lecture 2 April-12-11 10:33 AM Cell-Cell communication & Compartmentalization Procaryote unicellular organism; cells lack membrane bound nuclei; Eukaryote cell or organism having membrane-bound,structurally discrete nucleus other well-developedsubcellular compartments. Includes all organisms except viruses, bacteria, & cyanobacteria Gap Junctions: - Integral membrane proteins called connexin - Regulate passage of ions between two adjacent cells Thermodynamics The committingstep catalyzes a reaction that has a large free energy change (irreversible step) The other enzyme reactions are characterized by a relatively lower free energy change Entropy: Oxidation of glucose: small number of relatively complex/orderedmoleculesto a larger number of simpler molecules(increased entropy) Energy released ! Creating order has a cost but that order has potential energy Potential energy from one reaction can be used to drive another one Role of ATP: The chemical intermediate linking energy-releasingcatabolic (exergonic) reactions with energy demanding anabolic (endergonic) reactions Controls occur at the beginning of a pathway Inhibition and Allostery Inhibition: - Non-reactant molecule that resembles the substrate interferes with access of the normal substrate to the substrate binding pocket - Endogenous inhibitor is feedback inhibitor or negative effector,exogenous inhibitors are poisons Allostery - Binding of a ligand at one site affects binding of another at another site - Structural alterations interfere with the accessibility of other ligands, substrates or cofactors, or may disturb the catalytic site. Allosteric enzymesexist in at least two different states (controlledby the regulatory substances): R state (R= relaxed): high affinity for substrate T state (T = tense): low or no affinity for substrate - Allosteric activatorsand inhibitors induce conversionfrom the T to the R state, and the R to the T state, respectively. - Example of this is fructose 1,6-bisphosphate which inactivates glycerol kinase into its tetramericform when there is sufficient glucose present Control by post-translational modifications Transcriptionalcontrol: controlling level of mRNA expression e.g., PPARs and their PPREs Translational control: at initiation, elongation and termination steps in conversionof mRNA to protein To modulate the activities of enzymes already synthesized For acute control of enzyme activities (milli-seconds to minutes) Covalent Modifications: - Phosphorylation,methylation,acetylation,etc - Reversible - Turn active site on or off Control By enzyme turnover Control By enzyme turnover - Ubiquitin pathway important for control of enzyme turnover - Moleculeswith the PEST motif survive for only about 2-3 mins - Proteins lacking PEST motif have a half life of about 10 hours
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