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Ch 4: Cellular Metabolism - Part 2 Energy as it relates to Biology Enzymes Metabolism Catabolism (ATP production) Glycolysis and the TCA Cycle Anabolism (Synthetic pathways) Protein Synthesis Developed by John Gallagher, MS, DVM Metabolism Definition = “All chemical reactions that take place within an organism.” Metabolic pathways = network of linked reactions Basic feature: coupling of exergonic rxs with endergonic rxs. (direct vs. indirect coupling) Review: Energy = capacity to do work Usually from ATP Enzymes = biological catalyst Lower activation energy Return to original state Opportunity for control Metabolism p 101 Catabolism Energy Anabolism Synthesis Energy transferred commonly measured in calories: 1 cal = 1 g of H2O by 1° C 1 Kcal = temp. of 1L H2O by 1o C. = Calorie (capital C) Energy released in catabolic reactions is trapped in 1) Phosphate bonds 2) Electrons Metabolic pathways: Network of interconnected chemical reactions Linear pathway Intermediates Circular pathway Branched pathway Control of Metabolic Pathways (Chapter 6) 1. Enzyme concentration (already covered) 2. Enzyme modulators - Feedback- or end product inhibition - Hormones - Other signaling molecules 3. Different enzymes for reversible reactions 4. Enzyme isolation 5. Energy availability (ratio of ADP to ATP) Catabolic Pathways: ATP-Regeneration Amount of ATP produced reflects on usefulness of metabolic pathways: Aerobic pathways Anaerobic pathways Different biomolecules enter pathway at different points ATP = Energy Carrier of Cell (not very useful for energy storage) ATP Cycle ATP : ADP ratio determines status of ATP synthesis reactions Glycolysis From 1 glucose (6 carbons) to 2 pyruvate (3 carbons) molecules Main catabolic pathway of cytoplasm Does not require O2 common for (an)aerobic catabolism Starts with phosphorylation of Glucose to Glucose 6-P (“Before doubling your money you first have to invest!”) The Steps of Glycolysis Net gain? Pyruvate has 2 Possible Fates: Anaerobic catabolism: Pyruvate Lactate Aerobic catabolism: Pyruvate Citric Acid Cycle Citric Acid Cycle Other names ? Takes place in ? Energy Produced: 1 ATP 3 NADH 1 FADH2 Electron transport System Waste – 2 CO2 Energy Yield of Krebs Cycle NADH See Fig. 4-24 NADH NADH FADH2 Final step: Electron Transport System Chemiosmotic theory / oxidative phosphorylation Transfers energy from NADH and FADH2 to ATP (via e- donation and H+ transport) Mechanism: Energy released by movement of e- through transport system is stored temporarily in H+ gradient NADH produces a maximum of 2.5 ATP FADH2 produces a maximum of 1.5 ATP 1 ATP formed per 3H+ shuttled through ATP Synthase Fig 4-25 Summary of CHO catabolism Cellular Respiration Maximum potential yield for aerobic glucose metabolism: 30-32 ATP synthesized from ADP H2O is a byproduct Protein Catabolism?? Proteases Peptidases Deamination (removal of the NH3) NH3 becomes urea Pyruvate, Acetyl CoA, TCA intermediates are left. Lipid Catabolism?? Lipolysis Lipases break lipids into glycerol (3-C) Glycerol enters the glycolytic pathway Called β-oxidation Synthetic Pathways Anabolic reactions synthesize large biomolecules Unit molecules Glucose Amino Acids Macromolecules nutrients & energy required Polysaccharides Lipids DNA Protein Glycogen Synthesis Made from glucose Stored in all cells but especially in Liver (keeps 4h glycogen reserve for between meals) Skeletal Muscle muscle contraction Gluconeogenesis Glycolysis in reverse From glycerol, aa and lactate All cells can make G-6-P, only liver and Kidney can make glucose Protein Synthesis Proteins are necessary for cell functions Protein synthesis is under nuclear direction DNA specifies Proteins ? DNA mRNA ? Protein Redundancy of Genetic Code (p 115) A combination of three bases forms a codon 1 start codon 3 stop codon 60 other codons for 19 aa Transcription DNA is transcribed into complementary mRNA by RNA Polymerase + nucleotides + Mg2+ + ATP Gene = elementary unit of inheritance Compare to Fig. 4-33 Protein synthesis fig 4-27 Translation mRNA is translated into string of aa (= polypeptide) 2 important components ?? mRNA + ribosomes + tRNA meet in cytoplasm Anticodon pairs with mRNA codon aa determined Amino acids are linked via peptide bond. Fig 4-34 Primary Structure Post – Translational protein modifications: Folding, cleavage, additions glyco- , lipo- proteins Protein Sorting No signal sequence protein stays in cell Signal sequence protein destined for translocation into organelles or for export For “export proteins”: Signal sequence leads growing polypeptide chain across ER membrane into ER lumen Modifications in ER Transition vesicles to Golgi apparatus for further modifications Transport vesicles to cell membrane DNA Replication Semiconservative DNA polymerase