Biochemical Energy Production Chapter Twenty Three Biochemical Energy Production

Metabolism The sum total of all the biochemical reactions that take place in a living organism

Cell Structure Metabolic Reactions occur in specific sites within cells Typical animal cell Nucleus Chromosomes in the nucleus contain genetic material Cytoplasm is material between nucleus and cell membrane Mitochondria are where energy-producing reactions occur

Biochemical Energy Production

Biochemical Energy Production © R. Bhatnagar / Visuals Unlimited (a) Representation of a mitochondria. (b) micrograph of a mitochondria crista.

ATP Energy is released as food is oxidized Used to form ATP from ADP and Pi ADP + Pi + Energy ATP In cells, energy is provided by the hydrolysis of ATP (31 kJ/mole of ATP) ATP ADP + Pi + Energy

Biochemical Energy Production

High-Energy Phosphate Compounds Phosphate containing compounds that have a greater free energy of hydrolysis than that of a typical compound The energy of hydrolysis is large because of strong repulsive forces between electronegative atoms Enough energy is released by their hydrolysis to compensate for the energy needed for ATP production

Major Coenzymes in Metabolic Reactions NAD+/NADH FAD/FADH2 Coenzyme A (CoA-SH)

Major Coenzymes in Metabolic Reactions (a) Flavin adenine nucleotide (b) nicotinamide adenine dinucleotide

Major Coenzymes in Metabolic Reactions

Biochemical Energy Production Structural formula for coenzyme A CoA-SH

Coenzyme NAD+ In cells, the oxidation of compounds provides 2H as 2H+ and 2e- that reduce coenzymes NAD+ (nicotinamide adenine dinucleotide) participates in reactions that produce a carbon-oxygen double bond (C=O) Oxidation CH3-CH2-OH  CH3-CHO + 2H+ + 2e- Reduction NAD+ + 2H+ + 2e-  NADH + H+

Coenzyme FAD FAD participates in reactions that produce a carbon-carbon double bond (C=C) Oxidation -CH2-CH2-  -CH=CH- + 2H+ + 2e- Reduction FAD + 2H+ + 2e-  FADH2

Biochemical Energy Production Classification of metabolic intermediate compounds in terms of function.

Free Energies of Hydrolysis of Phosphate Containing Compounds

Biochemical Energy Production Hans Adolf Krebs received the Nobel Prize in medicine. Hulton Archive / Getty Images

Stages of Metabolism Catabolic reactions are organized as stages In Stage 1, digestion breaks down large molecules into smaller ones that enter the bloodstream. In Stage 2, molecules in the cells are broken down to two- and three-carbon compounds

Digestion of Foods Digestion is the first step of catabolism Carbohydrates glucose, fructose, galactose Proteins amino acids Lipids glycerol fatty acids

Stages of Metabolism In Stage 3, compounds are oxidized in the citric acid cycle to provide NADH and FADH2 molecules (reduced forms of coenzymes) In Stage 4, NADH and FADH2 are oxidized in order to provide energy for the production of ATP

Citric Acid Cycle The citric acid cycle: Operates under aerobic conditions only Oxidizes the two-carbon acetyl group in acetyl CoA to CO2 Produces reduced coenzymes NADH and FADH2 and one ATP directly

Reaction 1: Formation of Citrate Oxaloacetate combines with the two carbon acetyl group to form citrate

Reaction 2: Formation of Isocitrate Citrate isomerizes to isocitrate The tertiary –OH group in citrate is converted to a secondary –OH group that can be oxidized

Reaction 3: Oxidative Decarboxylation (1) A decarboxylation removes a carbon as CO2 from isocitrate. The –OH group is oxidized to a ketone, releasing H+ and 2e- that form reduced coenzyme NADH

Reaction 4: Oxidative Decarboxylation (2) In a second decarboxylation, a carbon is removed as CO2 from a-ketoglutarate The 4-carbon compound bonds to coenzyme A, providing H+ and 2e- to form NADH

Reaction 5: Hydrolysis The hydrolysis of the thioester bond releases energy to add phosphate to GDP and form GTP, a high energy compound

Reaction 6: Dehyrogenation In this oxidation, two H are removed from succinate to form a double bond in fumarate FAD is reduced to FADH2

Reaction 7: Hydration of Fumarate Water is added to the double bond in fumarate to form malate

Reaction 8: Dehyrogenation Another oxidation forms a C=O bond The hydrogens from the oxidation form NADH + H+

Summary of Products in the Citric Acid Cycle Oxaloacetate bonds with an acetyl group to form citrate Two decarboxylations remove two carbons as 2CO2 Four oxidations provide hydrogen for 3NADH and one FADH2 A direct phosphorylation forms GTP

Overall Chemical Reaction for the Citric Acid Cycle Acetyl CoA + 3NAD+ + FAD + GDP + Pi + 2H2O 2CO2 + 3NADH + 2H+ + FADH2 + HS-CoA + GTP

Regulation of Citric Acid Cycle Low levels of ATP stimulate the formation of acetyl CoA for the citric acid cycle High ATP and NADH levels decrease the formation of acetyl CoA and slow down the citric acid cycle

Regulation of Citric Acid Cycle The citric acid cycle: Increases its reaction rate when low levels of ATP or NAD+ activate isocitrate dehydrogenase Slows when high levels of ATP or NADH inhibit citrate synthetase (first step in cycle)

Electron Carriers Electron carriers: Accept hydrogen and electrons from the reduced coenzymes NADH and FADH2 Are oxidized and reduced to provide energy for the synthesis of ATP

Oxidation-Reduction Electron carriers are continuously oxidized and reduced as hydrogen and/or electrons are transferred from one to the next Electron carrier A (reduced) Electron carrier B (oxidized) Electron carrier A (oxidized) Electron carrier B (reduced)

Electron Transport Chain A series of biochemical reactions in which electrons and hydrogen ions from NADH and FADH2 are passed to intermediate electron carriers and then ultimately react with molecular oxygen to produce water Most of the enzymes for the Electron Transport Chain are found in the inner mitochondrial membrane (found in the order in which they are needed)

Biochemical Energy Production

Biochemical Energy Production (a) The oxidized form and reduced form of the electron carrier flavin mononucleotide. (b) The oxidized form and reduced form of the electron carrier coenzyme Q.

Biochemical Energy Production (a) CoQH2 carries electrons from both complexes I and II to complex III. (b) NADH is the substrate for the complex I and FADH2 is the substrate for complex II.

Biochemical Energy Production Electron movement through Complex III is initiated by the electron carrier CoQH2.

Biochemical Energy Production The electron-transfer pathway through Complex IV.

Biochemical Energy Production

Biochemical Energy Production Protein complexes I, III, and IV also act as proton pumps.

Chemiosmotic Model In the chemiosmotic model: Complexes I, III, and IV pump protons into the intermembrane space, creating a proton gradient. Protons must pass through ATP synthase to return to the matrix The flow of protons through ATP synthase provides the energy for ATP synthesis (oxidative phosphorylation) ADP + Pi + Energy  ATP

ATP Synthase ATP Synthase has two portions: Protons flow back to the matrix through a channel in the F0 complex. Proton flow provides the energy that drives ATP synthesis by the F1 complex

ATP Production for the Common Metabolic Pathway For every mole of NADH oxidized in the ETC, 2.5 moles of ATP are formed 3 formed in one turn of citric acid cycle (7.5 ATP) For every mole of FADH2 oxidized in the ETC, 1.5 moles of ATP are formed 1 formed in one turn of citric acid cycle (1.5 ATP) GTP is the equivalent of ATP 1 formed in one turn of the citric acid cycle (1 ATP) 10 ATP Overall!!!

Biochemical Energy Production The interconversion of ATP and ADP is the principal medium for energy exchange in the biochemical processes.