Energy Transformation: Cellular Respiration Outline 1. Sources of cellular ATP 2. Turning chemical energy of covalent bonds between C-C into energy

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1 Energy Transformation: Cellular Respiration Outline 1. Sources of cellular ATP 2. Turning chemical energy of covalent bonds between C-C into energy for cellular work (ATP) 3. Importance of electrons and H atoms in oxidation-reduction reactions in biologicalsystems 4. Cellular mechanisms of ATP generation 5. The four major central metabolic pathways Glycolysis- Fermentation Transition step Krebs Cycle Electron Transport chain and oxidative phosphorylation 4. Poisons of cellular respiration and their mechanisms of action. 5. Use of biomolecules other than glucose as carbon skeletons & energy sources

2 A cell has enough ATP to last for about three seconds

3 Necessary ATP is supplied to muscle cells by 1. Phosphagen system (8 to 10 seconds.) 2. Glycogen-lactic acid system (90 seconds)- glucose 3. Aerobic Respiration (unlimited)- glucose

4 Phosphagen system (muscle fibers) Creatine phosphate contains (a high-energy phosphate compound). Creatine kinase transfers the phosphate to ADP to form ATP. Creatine-Phosphate (tri) * Creatine-Phosphate + ADP (Tri) Creatine Kinase Creatine-Phosphate + ATP (Di) (*) Arezki Azzi et al. Protein Sci 2004; 13:

5 During cellular respiration the potential energy in the chemical bonds holding C atoms in organic molecules in turned into ATP. In presence of oxygen complete breakdown C-C-C-C-C-C + O 2 CO 2 + H 2 O + ATP large amount In absence of oxygen incomplete breakdown C-C-C-C-C-C 2 C-C-C + ATP small amount

6 Cellular respiration: ATP is produced aerobically, in the presence of oxygen Fermentation: ATP is produced anaerobically, in the absence of oxygen

7 Chemical bonds of organic molecules Chemical bonds involve electrons of atoms Electrons have energy Chemical bonds are forms of potential energy If a molecule loses an electron does it lose energy? When a chemical bond is broken sometimes electrons can be released

8 Oxidation-Reduction Oxidation: removal of electrons. Reduction: gain of electrons. Redox reaction: oxidation reaction paired with a reduction reaction.

9 Electron Carriers in Biological Systems The electrons associated with hydrogen atoms. Biological oxidations are often dehydrogenations Soluble electron carriers NAD +, and FAD (ATP generation) NADP + (biosynthetic reactions)

10 Nicotinamide Adenine Dinucleotide (NAD + ) a co-enzyme that acts as an electron shuttle (Niacin) 2 e + 2 H + 2 e + H + NAD + Dehydrogenase NADH H + Nicotinamide (oxidized form) + 2[H] (from food) Nicotinamide (reduced form) + H +

11 Flavin Adenine Dinucleotide (FAD+) is another co-enzyme that acts as an electron shuttle (Vitamin B2)

12 Oxidation In Metabolic pathways Reduction Energy loss or gain Exergonic or endergonic Catabolic or anabolic

13 In cells, energy is harvested from an energy source (organic molecule) by a series of coupled oxidation/reduction reactions (redox) known as the central metabolic pathways becomes oxidized becomes reduced Dehydrogenase

14 Metabolic Pathways Linear Pathways Branched Pathways Cyclic Pathways

15 An overview of the central metabolic pathways Glycolysis Transition step Tricarboxylic acid cycle (TCA or Krebs cycle) The Electron Transport Chain and oxidative phosphorylation

16

17 Mechanisms of ATP Generation during cellular respiration 1. Oxidative phosphorylation/ Chemiosmosis ADP and inorganic PO -4 ATP synthase Cellular respiration in mitochondria Electron Transport Chain

18 Generation of ATP 2. Substrate-level phosphorylation -Transfer of a high-energy - PO 4 from an organic moleculeto ADP - Different enzymes - During glycolysis and the TCA or Krebs cycle

19 Glycolysis Multi step breakdown of glucose into intermediates Turns one glucose (6-carbon) into two pyruvate (3-carbon) molecules Generates a small amount of ATP (substratelevel phosphorylation) Generates reducing power - NADH + H +

20 Figure 9.18 Pyruvate as a key juncture in catabolism

21 Fermentation An extension of glycolysis Takes place in the absence of oxygen (anaerobic) Regenerates NAD + from NADH + H + ATP generated by substrate - level phosphorylation during glycolysis Does not use the Krebs cycle or ETC (no oxidative - phosphorylation) A diversity of end products produced (i.e. lactic acid, alcohols, etc.)

22 Figure 9.17a Fermentation

23 Figure 9.17b Fermentation

24 Figure 9.9 A closer look at glycolysis: energy investment phase

25 Figure 9.9 A closer look at glycolysis: energy payoff phase

26 The energy input and output of glycolysis Energy investment phase Glucose Glycolysis Citric acid cycle Oxidative phosphorylation 2 ADP + 2 P 2 ATP used Energy payoff phase ATP ATP ATP 4 ADP + 4 P 4 ATP formed 2 NAD e + 4 H + 2 NADH + 2 H + 2 Pyruvate + 2 H 2 O Net Glucose 2 Pyruvate + 2 H 2 O 4 ATP formed 2 ATP used 2 NAD+ + 4 e + 4 H + 2 ATP 2 NADH + 2 H +

27 Transition step Under aerobic conditions, the pyruvate produced during glycolysis is directed to the mitochondrion. A multi-enzyme complex, spanning the 2 mitochondrial membranes, turns pyruvate (3-carbon) into Acetyl-CoA (2-carbon) and releases one CO 2 molecule Uses coenzyme A (Vit B derivative) Generates reducing power NADH + H +

28 Figure 9.10 Conversion of pyruvate to acetyl CoA, the junction between glycolysis and the Krebs cycle

29 Krebs or TCA Cycle A cyclical pathway Accepts acetyl CoA Generates 2 CO 2 molecules (for every acetyl-coa Generates reducing power NADH + H + and FADH 2 Generates a small amount of ATP (substrate-level phosphorylation)

30 A closer look at the Krebs cycle

31 Figure 9.12 A summary of the transition step and Krebs cycle

32 Figure 9.5 An introduction to electron transport chains

33 Electron Transport Chain and ATP Electron transport chain: membrane-embedded or bound electron carriers Mostly proteins with nonprotein groups. NADH vs. FADH 2 No direct formation of ATP Pumps H + into the intermembrane space generation

34 Oxidative Phosphorylation and ATP generation ATP Generation: Membrane-embedded protein complex, ATP synthase Proton-motive force Direct formation of ATP by Chemiosmosis Chemiosmosis: the coupling of the transport of H + across membrane by facilitated diffusion with chemical reaction producing ATP ATP Synthase Gradient: The Movie pgradient/movie.htm

35 Chemiosmosis couples the electron transport chain to ATP synthesis

36 Certain poisons interrupt critical events in cellular respiration Block the movement of electrons Block the flow of H + through ATP synthase Allow H + to leak through the membrane Rotenone Cyanide, carbon monoxide Oligomycin H + H + H + H + H + H + H + H + H + ATP Synthase DNP NADH H + NAD + FADH 2 H + FAD H + 1 O H + H 2 O ADP + P ATP Electron Transport Chain Chemiosmosis

37 Energy yield: How many ATP molecules are generated during cellular respiration of a single glucose molecule?

38 Sources of cellular glucose glucose from food in the intestine glycogen supplies in the muscles breakdown of the Liver's glycogen into glucose

39 The Catabolism of various food molecules Beta oxidation com/chemistry_d/templ ates/student_resources /shared_resources/ani mations/carnitine/carni tine1.html

40 Simple lipids Triglycerides consist of glycerol and fatty acids Fatty acids broken down into through beta oxidation

41 Proteins Protein Extracellular proteases Amino acids Deamination, decarboxylation, dehydrogenation Organic acid Krebs cycle and glycolysis Transition step

42 Feedback control of cellular respiration Phosphofructokinase Allosteric enzyme Activity modulated by inhibitors and activators Adjustment of cellular respiration in response to demand

43 Food, such as peanuts Carbohydrates Fats Proteins Sugars Glycerol Fattyacids Amino acids Amino groups Glucose G3P Pyruvate Acetyl GLYCOLYSIS CoA CITRIC ACID CYCLE OXIDATIVE PHOSPHORYLATION (Electron Transport and Chemiosmosis) ATP

44 Food molecules provide raw materials for biosynthesis consuming ATP ATP needed to drive biosynthesis ATP CITRIC ACID CYCLE Acetyl CoA Pyruvate GLUCOSE SYNTHESIS G3P Glucose Amino groups Amino acids Proteins Fatty acids Fats Glycerol Sugars Carbohydrates Cells, tissues, organisms