Metabolism All the chemical reactions in an organism

Catabolic pathways Break down complex molecules into simpler molecules Releases energy Examples? Digestive enzymes break down food to release energy

Anabolic pathway Build complex molecules from simple molecules Consume energy Example: Body links amino acids to form muscle in response to exercise

Free energy

Free energy G The available energy able to perform work when the temperature of a system is uniform Chemical reaction. In a cell, a sugar molecule is broken down into simpler molecules. . Diffusion. Molecules in a drop of dye diffuse until they are randomly dispersed. Gravitational motion. Objects move spontaneously from a higher altitude to a lower one. More free energy (higher G) Less stable Greater work capacity Less free energy (lower G) More stable Less work capacity In a spontaneously change The free energy of the system decreases (∆G<0) The system becomes more stable The released free energy can be harnessed to do work (a) (b) (c) Figure 8.5 

Exergonic reaction Energy is released Reactions are spontaneous (not necessarily quick) and release free energy into the system Figure 8.6 Reactants Products Energy Progress of the reaction Amount of energy released (∆G <0) Free energy (a) Exergonic reaction: energy released

Endergonic reaction Requires energy to proceed. Absorb free energy Figure 8.6 Energy Products Amount of energy released (∆G>0) Reactants Progress of the reaction Free energy (b) Endergonic reaction: energy required

Equilibrium and Metabolism Reactions in a closed system Eventually reach equilibrium Figure 8.7 A (a) A closed hydroelectric system. Water flowing downhill turns a turbine that drives a generator providing electricity to a light bulb, but only until the system reaches equilibrium. ∆G < 0 ∆G = 0

Cells in our body constant flow of materials in and out metabolic pathways cannot reach equilibrium Figure 8.7 (b) An open hydroelectric system. Flowing water keeps driving the generator because intake and outflow of water keep the system from reaching equlibrium. ∆G < 0

ATP - Adenine Phosphate groups Ribose Figure 8.8 NH2 HC CH C N O CH2 H OH N C HC NH2 Adenine Ribose Phosphate groups - CH

Energy coupling Use of exergonic process to drive an endergonic one Means that once ATP is made, the ATP can be used to fuel a process.

ATP Primary source of energy for coupling Made up of adenine bound to ribose and three phosphate groups When ATP is hydrolyzed energy is released in an endergonic reation

Energy is released from ATP When the terminal phosphate bond is broken Figure 8.9 P Adenosine triphosphate (ATP) H2O + Energy Inorganic phosphate Adenosine diphosphate (ADP) P i ATP drives endergonic reactions By phosphorylation, transferring a phosphate to other molecules

ADP When ATP is hydrolyzed it become ADP How many phophates does ADP have? ATP synthesis from ADP + P i requires energy ATP ADP + P i Energy for cellular work (endergonic, energy- consuming processes) Energy from catabolism (exergonic, energy yielding processes) ATP hydrolysis to ADP + P i yields energy Figure 8.12

Cellular respiration

Mitochondria Evidence suggests they were once free living prokaryotes Endosymbiotic theory

Evidence Bilayer membrane Circular DNA separate from that of nuclear DNA Contain ribosomes similar to those of bacteria Formation of new mitochondria is similar to binary fission Mitochondria and prokaryotes are similar size

Catabolic pathways Energy stored in chemical bonds is released when the bond is broken Released energy is used for work – the leftover is released as heat Called catabolism

2 types of Catabolism Fermentation – partial breakdown of sugars that occurs without oxygen

2 types of catabolism Cellular respiration – most efficient catabolic pathway Oxygen is consumed as a reactant, along with organic fuels such as carbohydrates, fats, and proteins to release energy Glucose is primary nutrient used in cellular respiration

Cellular respiration reaction C6H12O6 + 6O2 → 6 CO2 + 6 H2O + ATP Exergonic reaction (energy released is in the form of heat and ATP) ATP used to power all cellular activity

Phosphorylation When something gains a phosphate it is called phosphorylation. When a molecule loses a phosphate what the process called? Dephosphorylation

Stages of cellular respiration Glycolysis Citric acid cycle Oxidative phosphorylation: electron transport and chemiosmosis

Electrons carried via NADH ATP Substrate-level phosphorylation Fig. 9-6-1 Electrons carried via NADH Glycolysis Glucose Pyruvate Cytosol Figure 9.6 An overview of cellular respiration ATP Substrate-level phosphorylation

Electrons carried via NADH Electrons carried via NADH and FADH2 Fig. 9-6-2 Electrons carried via NADH Electrons carried via NADH and FADH2 Glycolysis Citric acid cycle Glucose Pyruvate Mitochondrion Cytosol Figure 9.6 An overview of cellular respiration ATP ATP Substrate-level phosphorylation Substrate-level phosphorylation

Electrons carried via NADH Electrons carried via NADH and FADH2 Fig. 9-6-3 Electrons carried via NADH Electrons carried via NADH and FADH2 Oxidative phosphorylation: electron transport and chemiosmosis Glycolysis Citric acid cycle Glucose Pyruvate Mitochondrion Cytosol Figure 9.6 An overview of cellular respiration ATP ATP ATP Substrate-level phosphorylation Substrate-level phosphorylation Oxidative phosphorylation

Substrate level phosphorylation ATP produced in glycolysis and krebs cycle by substrate level phosphorylation ATP made when enzyme transfers a phosphate group from a substrate molecule to ADP

Enzyme Enzyme ADP P Substrate + ATP Product Fig. 9-7 Figure 9.7 Substrate-level phosphorylation Product

Energy molecules in Cell Resp NAD+ (nicotiniacin) – coenzyme electron acceptor that acts as an oxidizing agent during cellular respiration NADH – when NAD+ receives 2 electrons, and a proton. Used to store energy *Similar molecules FAD, and FADH2

Glycolysis Location: cytosol (cytoplasm) Process 1. 6 -carbon glucose is split into 2 3 -carbon sugars 2. 3-carbon sugars are oxidized to form pyruvate

Net result Energy investment phase: Energy payoff phase: 2 ATP used to split glucose Energy payoff phase: 2 NAD+ is used, and reduced to 2 NADH Energy released from formation of NADH is used to produce 4 ATP BOTTOM LINE: How many ATP are produced? 2 ATP

Is glycolysis aerobic? NO!!! What was the point of making the NADH? Does not require oxygen What was the point of making the NADH? Remember it is an energy storing molecule! If oxygen is present, chemical energy stored in pyruvate and NADH can be used in the next phase of cellular respiratoin

Conversion of pyruvate 1. Pyruvate enters the mitochondrial matrix (active transport) 2. Enzymes catalyze the conversion of pyruvate into Acetyl coenzyme A or Acetyl CoA

CYTOSOL MITOCHONDRION NAD+ NADH + H+ 2 1 3 Acetyl CoA Pyruvate Fig. 9-10 CYTOSOL MITOCHONDRION NAD+ NADH + H+ 2 1 3 Acetyl CoA Figure 9.10 Conversion of pyruvate to acetyl CoA, the junction between glycolysis and the citric acid cycle Pyruvate Coenzyme A CO2 Transport protein

Citric acid cycle (Krebs cycle) Cycle with many steps, each of which is catalyzed by different enzymes. Is this process aerobic or anaerobic?

Pyruvate CO2 NAD+ CoA NADH + H+ Acetyl CoA CoA CoA Citric acid cycle 2 Fig. 9-11 Pyruvate CO2 NAD+ CoA NADH + H+ Acetyl CoA CoA CoA Citric acid cycle 2 CO2 Figure 9.11 An overview of the citric acid cycle FADH2 3 NAD+ FAD 3 NADH + 3 H+ ADP + P i ATP

Krebs cycle (con’t) Each turn of the cycle requires one acetyl CoA Must make 2 turns to get the products

Net results of Krebs Cycle 4 CO2 2 ATP 6 NADH 2 FADH2 Carbon is released during the krebs cycle! (remember the formula)

Review How many total molecules of ATP have been produced so far?

Oxidative phosphorylation Powered by redox reactions NADH and FADH2 are used in the next steps to make LOTS of ATP 90% of ATP made in cellular respiration made by this method

Electron transport chain Electron transport chain produces energy used to make ATP during oxidative phosphorylation

Figure 9.13 Free-energy change during electron transport NADH 50 2 e– NAD+ FADH2 2 e– FAD Multiprotein complexes  40 FMN FAD Fe•S  Fe•S Q  Cyt b Fe•S 30 Cyt c1 IV Free energy (G) relative to O2 (kcal/mol) Cyt c Cyt a Cyt a3 20 Figure 9.13 Free-energy change during electron transport e– 10 2 (from NADH or FADH2) 2 H+ + 1/2 O2 H2O

Electron transport chain Consists of molecules (mostly proteins) embedded in inner mitochondrial membrane Millions located in inner mitochondrial membrane!!

Electron transport chain Proteins have molecules on top that alternately oxidize and reduce Accepting electrons reduces Donating electrons oxidizes Initial electron acceptor is a flavoprotein (FMN) that accepts an electron from NADH

Figure 9.13 Free-energy change during electron transport NADH 50 2 e– NAD+ FADH2 2 e– FAD Multiprotein complexes  40 FMN FAD Fe•S  Fe•S Q  Cyt b Fe•S 30 Cyt c1 IV Free energy (G) relative to O2 (kcal/mol) Cyt c Cyt a Cyt a3 20 Figure 9.13 Free-energy change during electron transport e– 10 2 (from NADH or FADH2) 2 H+ + 1/2 O2 H2O

Electron transport chain FADH2 also donates electrons at a lower energy level!! Provides one-third less energy for ATP synthesis if electron donor is FADH2 instead of NADH

Electron transport chain Electrons are passed down a series of remaining molecules until they reach oxygen Most of the remaining molecules are called cytochromes Cytochromes-membrane bound, electron accepting proteins in the ETC

Figure 9.13 Free-energy change during electron transport NADH 50 2 e– NAD+ FADH2 2 e– FAD Multiprotein complexes  40 FMN FAD Fe•S  Fe•S Q  Cyt b Fe•S 30 Cyt c1 IV Free energy (G) relative to O2 (kcal/mol) Cyt c Cyt a Cyt a3 20 Figure 9.13 Free-energy change during electron transport e– 10 2 (from NADH or FADH2) 2 H+ + 1/2 O2 H2O

Electron transport chain FINAL ELECTRON ACCEPTOR – oxygen Binds with 2 hydrogen ions to form water (remember formula!!)

Look at the picture again. Where is high energy located? Where is low energy located? That means the reaction is endergonic or exergonic? exergonic

Result of electron transport chain Energy from electrons used to create a proton motive force that will be used in chemiosmosis to make ATP

Chemiosmosis Embedded in the mitochondrial inner membrane are ATP synthases. What does “ase” mean the protein is?

Chemiosmosis 1. Energy from ETC is used to pump H+ against concentration gradient (proton-motive force) What type of transport is this? 2. H+ move through ATP synthases down the concentration gradient 3. Movement of H+ drives the oxidative phosphorylation of ADP to ATP

i INTERMEMBRANE SPACE H+ Stator Rotor Internal rod Cata- lytic knob Fig. 9-14 INTERMEMBRANE SPACE H+ Stator Rotor Internal rod Figure 9.14 ATP synthase, a molecular mill Cata- lytic knob ADP + P ATP i MITOCHONDRIAL MATRIX

Electron transport chain 2 Chemiosmosis Fig. 9-16 H+ H+ H+ H+ Protein complex of electron carriers Cyt c V Q   ATP synthase  2 H+ + 1/2O2 H2O FADH2 FAD NADH NAD+ Figure 9.16 Chemiosmosis couples the electron transport chain to ATP synthesis ADP + P ATP i (carrying electrons from food) H+ 1 Electron transport chain 2 Chemiosmosis Oxidative phosphorylation

ATP production Glyolysis – 2 ATP Krebs cycle – 2 ATP Oxidative phosphorylation – 34 ATP TOTAL ATP – 36 ATP

Fig. 9-17 CYTOSOL Electron shuttles span membrane MITOCHONDRION 2 NADH or 2 FADH2 2 NADH 2 NADH 6 NADH 2 FADH2 Glycolysis Oxidative phosphorylation: electron transport and chemiosmosis 2 Pyruvate 2 Acetyl CoA Citric acid cycle Glucose + 2 ATP + 2 ATP + about 32 or 34 ATP Figure 9.17 ATP yield per molecule of glucose at each stage of cellular respiration About 36 or 38 ATP Maximum per glucose: