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Metabolism

Metabolism. A Little Biology. Animals rely on energy from the sun to do work. Heterotrophs or chemotrophs (that’s us) extract energy in the form of chemical bond energy to do work. Light energy to chemical bond energy. reduce CO 2  glucose. oxidize glucose  CO 2 . Animals. Plants.

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Metabolism

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  1. Metabolism

  2. A Little Biology Animals rely on energy from the sun to do work. Heterotrophs or chemotrophs (that’s us) extract energy in the form of chemical bond energy to do work. Light energy to chemical bond energy. reduce CO2  glucose oxidize glucose  CO2 Animals Plants

  3. The Big Picture In the conversion of glucose to CO2 energy is extracted in the form of chemical bond energy in discrete steps. Ultimately the carbon atoms from glucose  CO2 What is the fate of glucose under aerobic conditions? Biochemists like to use the word “fate” for “what happens to”. What is the fate of pyruvate during strenuous exercise? What is the fate of medical students after their biochemistry final exam?

  4. Metabolism • The sum total of all the chemical and physical changes that occur in a living system , which may be a cell, a tissue, an organ, or an organism. • The reactions of metabolism are almost all enzyme-catalyzed. • transformation of nutrients • excretion of waste products • energy transformations • synthetic and degradative processes

  5. Catabolism vs. Anabolism • Catabolism is the phase of metabolism that encompasses the breaking down and energy yielding reactions. • The cellular breakdown of complex substances and macromolecules

  6. Catabolism vs. Anabolism • Anabolism is the phase of metabolism that encompasses the making of biological molecules and require energy. • The cellular synthesis of complex substances and macromolecules smaller molecules.

  7. The Really Big Picture

  8. The Stages of Cellular Metabolism: A Preview • Metabolic Respiration is a cumulative function of three metabolic stages • Glycolysis • The citric acid cycle • Oxidative phosphorylation

  9. Glycolysis (glyco= glucose and lysis= split) • Breaks down glucose into two molecules of pyruvate • The citric acid cycle • Completes the breakdown of glucose

  10. Oxidative phosphorylation • Is driven by the electron transport chain • Generates ATP (Cell energy)

  11. 2 H + 1/2 O2 (from food via NADH) Controlled release of energy for synthesis ofATP 2 H+ + 2 e– ATP ATP Free energy, G Electron transport chain ATP 2 e– 1/2 O2 2 H+ H2O Figure 9.5 B (b) Cellular respiration

  12. Nuclear envelope ENDOPLASMIC RETICULUM (ER) NUCLEUS Nucleolus Rough ER Smooth ER Chromatin Flagelium Plasma membrane Centrosome CYTOSKELETON Microfilaments Intermediate filaments Ribosomes Microtubules Microvilli Golgi apparatus Peroxisome In animal cells but not plant cells: Lysosomes Centrioles Flagella (in some plant sperm) Lysosome Mitochondrion • A animal cell Figure 6.9

  13. Mitochondrion Intermembrane space Outer membrane Free ribosomes in the mitochondrial matrix Inner membrane Cristae Matrix Mitochondrial DNA 100 µm • Mitochondria are enclosed by two membranes • A smooth outer membrane • An inner membrane folded into cristae Figure 6.17

  14. Electrons carried via NADH and FADH2 Electrons carried via NADH Oxidativephosphorylation:electron transport andchemiosmosis Citric acid cycle Glycolsis Pyruvate Glucose Cytosol Mitochondrion ATP ATP ATP Substrate-level phosphorylation Oxidative phosphorylation Substrate-level phosphorylation Figure 9.6 • An overview of cellular respiration

  15. Enzyme Enzyme ADP P Substrate + ATP Product Figure 9.7 • Both glycolysis and the citric acid cycle • Can generate ATP by substrate-level phosphorylation

  16. Glycolysis harvests energy by oxidizing glucose to pyruvate • Glycolysis • Means “splitting of sugar” • Breaks down glucose into pyruvate • Occurs in the cytoplasm of the cell

  17. Glycolysis Oxidativephosphorylation Citricacidcycle ATP ATP ATP Energy investment phase Glucose P 2 ATP + 2 used 2 ATP Energy payoff phase formed P 4 ATP 4 ADP + 4 + 2 H+ 2 NADH 2 NAD+ + 4 e- + 4 H + 2 Pyruvate + 2 H2O Glucose 2 Pyruvate + 2 H2O 4 ATP formed – 2 ATP used 2 ATP + 2 H+ 2 NADH 2 NAD+ + 4 e– + 4 H + Figure 9.8 • Glycolysis consists of two major phases • Energy investment phase • Energy payoff phase

  18. CYTOSOL MITOCHONDRION + H+ NAD+ NADH O– CoA S 2 C O C O C O CH3 1 3 CH3 Acetyle CoA Pyruvate CO2 Coenzyme A Transport protein Figure 9.10 • Before the citric acid cycle can begin • Pyruvate must first be converted to acetyl CoA, which links the cycle to glycolysis

  19. Pyruvate(from glycolysis,2 molecules per glucose) Oxidativephosphorylation Glycolysis Citricacidcycle ATP ATP ATP CO2 CoA NADH + 3 H+ Acetyle CoA CoA CoA Citricacidcycle 2 CO2 3 NAD+ FADH2 FAD 3 NADH + 3 H+ ADP + Pi ATP Figure 9.11 • An overview of the citric acid cycle

  20. Electron shuttles span membrane MITOCHONDRION CYTOSOL 2 NADH or 2 FADH2 2 FADH2 2 NADH 2 NADH 6 NADH Glycolysis Oxidative phosphorylation: electron transport and chemiosmosis Citric acid cycle 2 Acetyl CoA 2 Pyruvate Glucose + 2 ATP + 2 ATP + about 32 or 34 ATP by oxidative phosphorylation, depending on which shuttle transports electrons from NADH in cytosol by substrate-level phosphorylation by substrate-level phosphorylation About 36 or 38 ATP Maximum per glucose: Figure 9.16 • There are three main processes in this metabolic enterprise

  21. Fats Carbohydrates Proteins Amino acids Fatty acids Sugars Glycerol Glycolysis Glucose Glyceraldehyde-3- P NH3 Pyruvate Acetyl CoA Citric acid cycle Oxidative phosphorylation Figure 9.19 • The catabolism of various molecules from food

  22. Glucose AMP Glycolysis Stimulates Fructose-6-phosphate + Phosphofructokinase – – Fructose-1,6-bisphosphate Inhibits Inhibits Pyruvate Citrate ATP Acetyl CoA Citric acid cycle Oxidative phosphorylation Figure 9.20 • The control of cellular respiration

  23. ATP • Chemical energy of the cell • The cell takes up glucose and converts it to cell energy (ATP) • Various forms of cell energy • ATP, ADP, AMP, Creatine phosphate

  24. The structure of ATP, ADP, and AMP adenine ribose ATP is most commonly hydrolyzed to ADP or AMP

  25. The structural Basis of High Phosphoryl Transfer Potential of ATP

  26. Creatine phosphate is a reservoir of high potential phosphoryl groups. Creatine kinase transfers phosphate to ADP to form ATP. This reaction is important in heart muscle after an Myocardial Infarction.

  27. Other Activated Carriers • Just as ATP carries and transfers phosphate other molecules carry electrons and participate in oxidation reduction reactions (i.e. NADH, NADH2, FADH2).

  28. The electrons are not directly transferred to O2. Electron carriers (i.e. NADH) Deliver Energy To ETS Electron Transfer System

  29. Nicotine Adenine Dinucleotide NADPH

  30. Generally, NAD+ participates in reactions where alcohols are converted to ketones/aldehydes and organic acids.

  31. Synthetic and degradative pathways are distinct. If [ATP] is low, degradative pathways are stimulated. If [ATP] is high, degradative pathways are inhibited. Degradation Synthesis

  32. Regulation of the degradation and synthesis of glucose and glycogen depends on the energy state of the cell • High [NADH] is indirectly equivalent to high[ATP]. This means that the cell is high in “energy”. • High [NAD+] or [ADP or AMP] means that the cell is low in “energy”. • These molecules (and others) can act as allosteric effectors stimulating or inhibiting allosteric enzymes which are usually at the beginning or branch-points of a specific pathway.

  33. Synthetic and Degradative Pathways Don’t Happen at the Same Time • They can share some common steps but they are never simply the reverse of one another. • Synthetic pathways always use more ATP than a degradative pathway will produce. • If both synthetic and degradative pathways occurred at the same time, “wasteful” hydrolysis of ATP would result. • This is termed a “futile cycle.”

  34. Regulation of synthetic and degradative pathways. • For example, phosphorylation activates glycogenolysis (breakdown of glucose) whereas phosphorylation inactivates glycogenesis (glycogen synthesis). • Put differently: Phosphorylation activates glycogenolysis whereas dephosphorylation activates glycogenesis. • On the same theme, the action of insulin is opposite to that of glucagon. • Insulin decreases blood glucose levels whereas glucagon increases blood glucose levels.

  35. In Summary

  36. Intrinsic Regulation • Molecules such as NAD+, NADH, ATP, ADP, AMP etc. are important intrinsic regulators of cellular metabolism. • the concentrations of these molecules mirror the energy charge of the cell and act as regulators of the cells’ metabolism. This is only one level of regulation.

  37. Extrinsic Regulation • Hormones are a higher order of regulation involving communication between cells, tissues, and the environment. • Many hormones (not all) interact with cell surface receptors and set off a cascade of molecular events which: • stimulate or repress the activity of key enzymes. • AND/OR • stimulate or repress the transcription of specific genes.

  38. Two hormones that are of particular importance and involve the regulation of catabolic and anabolic pathways are: INSULIN & GLUCAGON

  39. Insulin vs. Glucagon • In general: • Insulin operates through dephosphorylation mechanisms. • Glucagon operates through phosphorylation mechanisms.

  40. A fatty acid molecule (subunit of fat) is in a more reduced state than a molecule of glucose. Thus, more energy is extracted from the FA than CHO.

  41. What’s Next? • The endocrine lectures will deal with the degradation and synthesis of carbohydrates. • This will be followed by lectures dealing with the degradation and synthesis of fatty acids. • Some integrative of metabolism will then be discussed within a frame work of - “feeding, fasting, and exercising”

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