Biochemistry Unit V: Oxidative Phosphorylation and Metabolism PDF

# Unit-V: Oxidative Phosphorylation and Integration of Metabolism ## Oxidative Phosphorylation - **Chemiosmotic Theory**: Transmembrane differences in proton concentration are the reservoir for the energy extracted from biological oxidation-reduction reactions. - **General Steps**: 1. Flow of...

# Unit-V: Oxidative Phosphorylation and Integration of Metabolism ## Oxidative Phosphorylation - **Chemiosmotic Theory**: Transmembrane differences in proton concentration are the reservoir for the energy extracted from biological oxidation-reduction reactions. - **General Steps**: 1. Flow of electrons through a chain of membrane-bound carriers. 2. The free energy made available by this "downhill" (exergonic) electron flow is coupled to the "uphill" transport of protons across a proton-impermeable membrane, conserving the free energy of fuel oxidation as a transmembrane electrochemical potential. 3. Transmembrane flow of protons down their concentration gradient through specific protein channels provides the free energy for synthesis of ATP, catalyzed by a membrane protein complex (ATP synthase) that couples proton flow to phosphorylation of ADP. - **Oxidative Phosphorylation Begins** with the entry of electrons into the respiratory chain. Most of these electrons arise from the action of dehydrogenases that collect electrons from catabolic pathways and funnel them into universal electron acceptors - NAD+ or NADP+ or FMN or FAD. - **Ubiquinone/coenzyme Q, Cytochromes, and iron-sulfur proteins** also function as electron carriers. - **Sequentially Arranged Electron Carriers** (integral proteins with prosthetic groups). - Direct transfer of electrons (Fe^3+ reduced to Fe^2+). - Transfer as a hydrogen atom (H^+ + e^-). - Transfer as a hydride ion (:H-). ## Diagram of Oxidative Phosphorylation - The diagram shows a membrane with an intermembrane space (P side) and a matrix (N side). - There are four complexes: I, II, III, and IV, each of which transports protons across the membrane. - **Complex I** uses NADH as a source of electrons and transfers them to ubiquinone (Q). - **Complex II** uses succinate as a source of electrons and transfers them to ubiquinone (Q). - **Complex III** carries electrons from reduced ubiquinone to cytochrome c. - **Complex IV** completes the sequence by transferring electrons from cytochrome c to O2. ## Proton-Motive Force - The diagram shows a membrane with a P side and an N side. - The proton pump transports protons from the N side to the P side, creating a concentration gradient of protons across the membrane. - This gradient creates a **proton-motive force**, which drives the synthesis of ATP. ## Chemiosmotic Model - The diagram shows a membrane with an intermembrane space (P side) and a matrix (N side). - The electron transport chain pumps protons across the membrane, creating a proton gradient. - The proton gradient drives the synthesis of ATP by **ATP synthase**. - The chemical potential (ΔpH) is alkaline inside. - The electrical potential (Δψ) is negative inside. ## Rotational Catalysis - The conformational changes central to this mechanism are driven by the passage of protons through the Fo portion of ATP synthase. - The γ subunit rotates in one direction when FoF1 is synthesizing ATP and in the opposite direction when the enzyme is hydrolyzing ATP. ## ATP Yield from Complete Oxidation of Glucose | Process | Direct product | Final ATP | |------------------------------------------|---------------------------------|------------| | Glycolysis | 2 NADH (cytosolic) | 3 or 5\* | | | 2 ATP | 2 | | Pyruvate Oxidation (two per glucose) | 2 NADH (mitochondrial matrix) | 5 | | Acetyl-CoA Oxidation in Citric Acid Cycle | 6 NADH (mitochondrial matrix) | 15 | | (two per glucose) | 2 FADH2 | 3 | | | 2 ATP or 2 GTP | 2 | | Total yield per glucose | | 30 or 32 | \* The number depends on which shuttle system transfers reducing equivalents into the mitochondrion. ## Lipogenic Liver (Well-fed state) - The diagram shows a well-fed liver with insulin being produced by the pancreas. - Glucose is being taken up by the liver and stored as glycogen. - Fatty acids are synthesized by the liver and stored as triacylglycerols (TAG) in adipose tissue. - Insulin stimulates glucose uptake, glycogen synthesis, and fatty acid and triacylglycerol synthesis. ## Glucogenic Liver (Fasting State) - The diagram shows a fasting liver with glucagon being produced by the pancreas. - Glycogen is being broken down and used to produce glucose through gluconeogenesis. - Fatty acids are being broken down and used to produce ketone bodies which can be used as fuel by the brain. - Glucagon stimulates glycogen breakdown, gluconeogenesis, and fatty acid breakdown.