Cellular Respiration

 To get a better understanding of how cellular respiration takes place in our bodies at a cellular level please take the time to watch the following videos!   r-respiration/v/introduction-to-cellular-respiration r-respiration/v/introduction-to-cellular-respiration

 Process that extracts energy from food (mainly glucose, but also proteins and lipids) in the presence of oxygen – obligate aerobes  The energy that is extracted is used to synthesize ATP  ATP is used to supply energy directly to cells to drive chemical reactions

 Divided into 4 stages 1. Glycolysis 2. Pyruvate oxidation 3. Citric acid cycle 4. Electron transport and oxidative phosphorylation  Each Stage involves the transfer of FREE ENERGY  ATP is produced in two different ways Substrate-level phosphorylation Oxidative phosphorylation

 Location of each Stage Glycolysis  Cytosol Pyruvate Oxidation  Mitochondrion Citric Acid Cycle  Mitochondrion Electron Transport  Mitochondrion

 Primitive Process found in almost all organisms  Both prokaryotes and eukaryotes  Does not require O ₂  Involves Soluble enzymes  10 sequential enzyme-catalyzed reactions Oxidation of a 6-carbon sugar glucose  Produces 2 molecules of pyruvate (3-carbon molecule) 2 ATP and 2 NADH  Two Phases in which this occurs Initial energy investment phase Energy payoff phase This process is for the conversion of only ONE glucose molecule!!! hill.com/sites/ /stude nt_view0/chapter25/animation__ how_glycolysis_works.html

 Step 1 Glucose receives a phosphate group from ATP Produces glucose-6-phosphate  Enzyme used hexokinase

 Step 2 Glucose-6-phosphate is rearranged into its isomer Produces fuctose-6-phosphate  Enzyme used Phospho-glucomutase  Recall Isomers Same molecular formula but different structure

 Step 3 Fructose-6-phosphate receives another phosphate group from ATP Produces fructose-1,6-bisphosphate  Enzyme Used Phospho-fructokinase

 Step 4 Fructose-1,6-bisphosphate is split Produces  Glyceraldehyde-3-phosphate (G3P)  Dihydroxyacetone phosphate (DHAP)  Enzyme used aldolase

 Step 5 Dihydroxyacetone (DHAP) is converted Produces  glyceraldehyde-3-phosphate (G3P)  Enzyme used Triosephosphate-isomerase  This is the last step of the initial energy investment phase Total of 2 ATP invested End result is 2 G3P molecules

Because there are now 2 molecules of G3P at the end of the initial energy investment phase, all the reactions in the energy payoff phase (6 to 10) are DOUBLED!!

 Step 6 2 electrons and 2 protons are removed from G3P NAD ⁺ accepts both electrons and a proton (becoming NADH) Other proton is released into cytosol Phosphate group is attached Produces  Two 1,3-bisphosphoglycerate  Enzyme used Triosephosphate-dehydrogenase

 Step 7 A phosphate group from 1,3-bisphosphoglycerate is transferred to ADP Produces 2 ATP Two 3-phosphoglycerate  Enzyme used Phosphoglycerate kinase  ATP is produced by Substrate-level phosphorylation

 Step 8 3-phosphoglycerate is rearranged Phosphate group is shifted from 3- carbon to 2-carbon Produces  Two 2-phosphoglycerate  This process is done via mutase reaction Shifting of a chemical group to another within the same molecule  Enzyme used phosphoglucomutase

 Step 9 Electrons are removed from one part of 2-phosphoglycerate and delivered to another part of the molecule Produces  Two H ₂ O molecules  Two Phosphoenolpyruvate  Enzyme used Enolase

 Step 10 Final phosphate group is transferred from phosphoenolpyruvate (PEP) to ADP Produces  2 ATP  Two Pyruvate molecules  Enzyme used Pyruvate kinase  ATP is produced by Substrate-level phosphorylation

 Phosphate groups are attached to ADP from a substrate forming ATP (enzyme catalyzed reaction)  ALL ATP molecules are produced this way in Glycolysis

 Initial energy investment phase 2 ATP are consumed  Energy payoff phase 4 ATP produced 2 NADH molecules are synthesized Overall NET reaction; Glucose + 2 ADP + 2 P i + 2 NAD ⁺ → 2 pyruvate + 2 ATP + 2 NADH + 2H ⁺  62 kJ of energy is stored by the synthesis of 2 ATP molecules  Rest of the free energy is stored in the 2 pyruvate molecules

 Remember glycolysis occurs in the cytosol of the cell  The Citric Acid Cycle (next step) occurs in the mitochondrial matrix  Pyruvate must pass through the inner and outer membrane of the mitochondrion

 Multi-step process Outer membrane  Pyruvate diffuses across the outer membrane through large pores of mitochondrion Inner membrane  Pyruvate-specific membrane carrier is required Inside Matrix  Pyruvate is converted into an acetyl group  Acetyl group is bonded to coenzyme A  Produces an acetyl-CoA complex

Conversion of pyruvate to acetyl-CoA Involves 2 Reactions 1. Decarboxylation reaction  Carboxyl group (-COO ⁻ ) of pyruvate is removed  Produces  CO ₂ 2. Dehydrogenation reaction  2 electrons and a proton are transferred  Produces  NADH  H ⁺ in solution Net reaction 2 pyruvate + 2 NAD ⁺ + 2 CoA → 2 acetyl-CoA + 2 NADH + 2 H⁺ + 2 CO₂

 Acetyl group reacts with the sulfur atom of coenzyme A  Acetyl-CoA is the molecule that will start the Citric Acid Cycle

 Discovered by Sir Hans Krebs ( ) Consists of 8 enzyme catalyzed reaction ALL ATP are produced by substrate-level phosphorylation hill.com/sites/ /student_view0/chapte r25/animation__how_the_krebs_cycle_works__qu iz_1_.html hill.com/sites/ /student_view0/chapte r25/animation__how_the_krebs_cycle_works__qu iz_1_.html

 Step 1 2-carbon acetyl group carried by coenzyme A is transferred to oxaloacetate Produces  Citrate  Enzyme used Citrate synthase

 Step 2 Citrate is rearranged into its isomer Produces  Isocitrate  Enzyme used Aconitase

 Step 3 Isocitrate is oxidized Produces  α-ketoglutarate  NADH  CO ₂  H ⁺  Enzyme used Isocitrate dehydrogenase

 Step 4 α-ketoglutarate is oxidized Produces  Succinyl CoA  CO ₂  NADH  Enzyme used α-ketoglutarate dehydrogenase

 Step 5 CoA is released from succinyl CoA Produces  Succinate  Energy released converts GDP to GTP which couples production of ATP  Enzyme used Succinyl CoA synthetase  GTP Activates substrate to produce ATP

 Step 6 Succinate is oxidized Produces  Fumarate  FADH ₂  Enzyme used Succinate dehydrogenase  FADH ₂ Nucleotide-based molecule Electron carrier

 Step 7 Fumarate is converted with the addition of H ₂ O Produces  Malate  Enzyme used Fumarase

 Step 8 Malate is oxidized Produces  Oxaloacetate  NADH  H ⁺  Enzyme used Malate dehydrogenase

 2 molecules of pyruvate are converted to Acetyl-CoA  Citric Acid Cycle goes through two turns for every single glucose molecule that is oxidized 1 Turn: Acetyl-CoA + 3 NAD ⁺ + FAD + ADP + P i → 2 CO ₂ + 3 NADH + 3 H ⁺ + FADH ₂ + ATP + CoA ATP is synthesized by substrate level phosphorylation coupled by GTP

 ALL of the carbon atoms that make up a glucose molecule are converted into CO ₂ oxidation of pyruvate acetyl groups

Total # of NET Molecules Produced NADH FADH ₂ CO ₂ ATP Glycolysis2002 Pyruvate Oxidation 2020 Citric Acid Cycle 6242

 Process that extracts potential energy that is stored in NADH and FADH ₂ These molecules were formed during glycolysis, pyruvate oxidation, and citric acid cycle  This energy is used to synthesize additional ATP (A lot more)

 Occurs on the inner mitochondrial membrane  Facilitates the transfer of electrons from NADH and FADH ₂ to O ₂

 Composed of 4 Complexes  Complex I, NADH dehydrogenase  Complex II, succinate dehydrogenase  Complex III, cytochrome complex  Complex IV, cytochrome oxidase 2 Electron shuttles  Ubiquinone (UQ)  Hydrophobic molecule – shuttles electrons from complex I and II to complex III  Cytochrome C (cyt c)  Shuttles electrons from complex III to complex IV

 Complexes I, III, IV Each has a cofactor  Each cofactor has increasing electronegativity  Alternate between reduced and oxidized states  Electrons move towards more electronegative molecules (downstream)  Final electron acceptor – OXYGEN (most electronegative)  Pulls electrons from complex IV  hill.com/sites/ /student_view0/chapter25/animation__electron_transport_system_and_atp_synthesis__quiz_1_.htm l hill.com/sites/ /student_view0/chapter25/animation__electron_transport_system_and_atp_synthesis__quiz_1_.htm l

 Final electron acceptor Removes two electrons from complex IV Reacts with 2 H ⁺ to produce H ₂ O  BUT WE BREATH IN O ₂ NOT A SINGLE O  So for every O ₂ molecule Pulls a total of 4 electrons through the electron transport chain 2 H ₂ O molecules are produced  Pulling 4 electrons from complex IV triggers a chain reaction between other complexes!!

 Starts with O ₂  Pulls electrons through the chain of complexes  NADH is least electronegative but contains most free energy  O ₂ has highest electronegativity but contains least amount of free energy

 Electron Transport from NADH or FADH ₂ to O ₂ does not produce any ATP!!  What does?  Proton Gradient Transport of H ⁺ ions across the inner mitochondrial membrane from the matrix into the inter-membrane space  Creates  Proton-Motive Force Chemical gradient (difference in concentrations) Electro potential gradient is created (because of the positive charge on Hydrogen atom)

 The ability of cells to use the proton- motive force to do work  Synthesizes ATP using electrochemical gradient  Uses ATP synthase enzyme ATP is synthesized using oxidative phosphorylation

 Relies on ATP synthase Forms a channel which H ⁺ ions can pass freely H ⁺ ions cause the synthase to rotate harnessing potential energy to synthesize ATP

 NADH produced during glycolysis is in cytosol Transported into mitochondria via two shuttle systems  Malate-aspartate shuttle  Glycerol-phosphate shuttle Glycolysis2 ATP Citric Acid Cycle2 ATP Electron Transport34 ATP Total38 ATP

 For every NADH that is oxidized About 3 ATP are synthesized 10 NADH x 3 ATP = 30 ATP  For every FADH ₂ About 2 ATP are synthesized 2 FADH ₂ x 2 ATP = 4 ATP  Total of 34 ATP synthesized by electron transport chain

 38 ATP produced  Hydrolysis of ATP yields 31kJ/mol  31 kJ/mol x 38 ATP = 1178 kJ/mol  Glucose contains 2870 kJ/mol of energy Only 41% of the energy in glucose in converted into ATP The rest is lost as thermal energy

 Brain cells, muscle cells Need burst of ATP during periods of activity  Creatine phosphate pathway Creatine is phosphorylated High energy molecule Stored within cell Used to generate additional ATP when needed creatine + ATP → creatine phosphate + ADP creatine phosphate → creatine + ATP

 Uncoupling Proteins in mitochondria provide a different path for H ⁺ Instead of producing ATP, thermal energy is released  Brown adipose tissue Important for the maintenance of body temperature  Hibernating mammals

 Amount of energy an organism expends over a specified time Increase energy use when work increses  Basal metabolic rate (BMR) kJ/m²/h Amount of energy used during a state of rest Higher % of body fat reduces metabolic rate

 Regulated Feedback inhibition  Enzyme used Phosphofructokinase  Inhibited by High levels of ATP High levels of citrate  Activated by Low levels of ADP Low levels of AMP  Glucose Stored as glycogen

 Disaccharide carbohydrates Hydrolyzed into glucose, fructose, galactose Glycogen is hydrolyzed by enzymes in liver  Produce glucose-6-phosphate  Fats Triglycerides  Hydrolyzed into glycerol  Converted into glyceraldehyde-3-phosphate  Fatty Acids  Split into 2 carbon fragments  Become acetyl groups – attach to CoA  Proteins Hydrolyzed into amino acids  -NH ₂ is removed and the rest enters as pyruvate, acetyl groups

 Two pathways Fermentation (not a form of respiration)  Uses an organic molecule as a final electron acceptor  Does not use an electron transport chain Anaerobic respiration  Uses an inorganic substance as the final electron acceptor  Uses an electron transport chain

 Absence of oxygen  Reactions used to oxidize NADH Allows glycolysis to continue  Two forms Ethanol fermentation Lactic acid fermentation

 Occurs in Bacteria, yeasts  Process Pyruvate is decarboxylated Produces acetaldehyde Acetaldehyde oxidizes NADH  Products CO ₂ Ethanol NAD ⁺ Facultative anaerobes - survive with or without oxygen

 Final reaction: pyruvate + NADH + H ⁺ → NAD ⁺ + CO ₂ + ethanol  Glycolysis included (2 pyruvate molecules) glucose + 2 ADP + 2 P i → 2 ATP + 2CO ₂ + 2 ethanol Fermentation produces only 2 ATP!!!

 Occurs in humans when Demand for ATP exceeds the rate at which O ₂ can be supplied  Process Pyruvate is converted into lactate Lactate regenerates NAD ⁺ Glycolysis continues

 Final reaction pyruvate + NADH + H ⁺ → NAD ⁺ + lactate  Glycolysis included glucose + 2 ADP + 2P i → lactate + 2ATP Fermentation only produces 2 ATP!!!

 Obligate anaerobes Cannot survive in the presence of oxygen Lack mitochondria Have electron transport chains Inorganic terminal electron acceptor  Sulfate SO ₄ ² ⁻  Nitrate NO ₃⁻  Iron ion Fe³ ⁺ Many prokaryotes, protists