Biochemistry Chapter: Cellular Respiration

Electron Transport Chain Overview

• The Electron Transport Chain (ETC) is vital for cellular respiration, located in the inner mitochondrial membrane.
• It drives ATP production through oxidative phosphorylation.
• The process starts with electrons from reduced substrates (NADH and FADH2), generated in glycolysis and the citric acid cycle.
• These electrons are transferred through protein complexes (I, II, III, IV) and electron carriers, ultimately reducing oxygen to form water.
• Energy released during electron flow pumps protons (H+) from the mitochondrial matrix to the intermembrane space, creating an electrochemical gradient.
• This gradient provides the energy for ATP synthase to convert ADP and inorganic phosphate (Pi) to ATP.

Oxidative Fuel Production

• The ETC is part of a larger process, including glycolysis and the citric acid cycle.
• These pathways supply the electron carriers (NADH and FADH2) for the ETC.
• NADH produces approximately 2.5 ATP molecules.
• FADH2 produces approximately 1.5 ATP molecules.
• Proton pumping coupled with electron flow establishes the essential proton gradient for ATP synthesis.

Mechanism of Proton Pumping

• The ETC involves four main complexes.
• Complex I accepts electrons from NADH, pumping 4 H+ ions into the intermembrane space.
• Complex II accepts electrons from FADH2 but does not pump protons.
• Complex III transfers electrons via the Q cycle, pumping 4 H+ across the membrane.
• Complex IV receives electrons from cytochrome c, reducing O2 to H2O and pumping 2 H+.
• The total protons pumped contribute to the proton-motive force that drives ATP synthesis.

Role of ATP Synthase

• ATP synthase utilizes the electrochemical potential from the proton gradient.
• As protons flow back into the mitochondrial matrix through ATP synthase, energy is released, converting ADP and inorganic phosphate (Pi) into ATP.
• This process is essential for cellular energy production.

Summary of Electron Transport Chain Process

• Electrons from NADH and FADH2 are transferred through the ETC.
• The transfer process pumps protons into the intermembrane space, creating a gradient.
• Oxygen acts as the final electron acceptor, forming water.
• The proton gradient drives ATP synthesis via ATP synthase.

Oxidative Phosphorylation

• Oxidative phosphorylation is a crucial metabolic process occurring in the mitochondria.
• It produces ATP through the electron transport chain (ETC) and chemiosmosis.
• The process uses energy from electron transfer from electron donors, such as NADH and FADH2, to oxygen (final electron acceptor).
• The overall reaction is NADH + 1/2O2 + H+ → NAD+ + H2O.
• Energy release from NADH-to-O2 transfer drives ATP synthesis.

Role of Electron Carriers

• Electron carriers (NADH and FADH2) play a critical role in oxidative phosphorylation.
• NADH produces approximately 2.5 ATP.
• FADH2 produces approximately 1.5 ATP.
• These carriers donate electrons to the ETC, passing them through protein complexes in the inner mitochondrial membrane.

Complex I: NADH Dehydrogenase

• Complex I, also known as NADH dehydrogenase, plays a key role in the electron transport chain (ETC).
• NADH is oxidized to NAD+ releasing two electrons (2e-).
• Electrons are transferred through Flavin mononucleotide (FMN) and Iron-sulfur clusters.
• Four protons (4H+) are pumped into the intermembrane space per two electrons transferred.
• Coenzyme Q (CoQ) receives transferred electrons and is reduced to QH2 (ubiquinol).

Complex II: Succinate Dehydrogenase

• Complex II, also known as succinate dehydrogenase, is part of the electron transport chain (ETC).
• It catalyzes the conversion of succinate to fumarate in the citric acid cycle.
• FAD is reduced to FADH2, releasing two electrons (2e-).
• Electrons are transferred through Fe-S clusters to CoQ, which reduces to QH2.
• Complex II does not pump protons (H+) across the inner mitochondrial membrane.

Complex III: Q-Cytochrome C Oxidoreductase

• Complex III, also known as Q-cytochrome c oxidoreductase, is involved in the electron transport chain (ETC).
• QH2 binds to heme bL, then heme bH, where it is oxidized to Q, releasing 2 protons (2H+) and two electrons (2e-).
• Electrons are transferred through iron-sulfur (Fe-S) clusters to cytochrome c, which then carries electrons to complex IV.
• Complex III pumps 4 protons into the intermembrane space during the Q cycle.

Complex IV: Cytochrome C Oxidase

• Complex IV (cytochrome c oxidase) is the final complex in the electron transport chain (ETC).
• It receives electrons from cytochrome c, requiring four cytochrome c molecules to transfer a total of 4 electrons.
• Electrons bind with copper subunits.
• Four protons (4H+) and O2 are used to reduce oxygen to form two water molecules (2H2O).
• Complex IV pumps two protons (2H+) into the intermembrane space per two electrons it transfers.

Summary of Proton Pumping

• Complex I pumps 4 protons.
• Complex II does not pump protons.
• Complex III pumps 4 protons.
• Complex IV pumps 2 protons.
• The proton-motive force generated by these complexes drives ATP synthesis by ATP synthase.

ATP Synthase Mechanism

• ATP synthase is a crucial enzyme for ATP production.
• It consists of F0 and F1 portions.
• The F0 portion is embedded in the inner mitochondrial membrane and is responsible for proton translocation.
• The F1 portion protrudes into the mitochondrial matrix and is the site of ATP synthesis.
• Protons flow back into the matrix through the F0 portion, driving the rotation of the c ring and the F1 portion, which catalyzes ATP synthesis from ADP and inorganic phosphate (Pi).

Shuttle Mechanisms

• Malate-Aspartate Shuttle: Electrons from cytosolic NADH are transferred to the mitochondrial matrix via malate and aspartate.
• Glycerol-3-Phosphate Shuttle: Transfers electrons from cytosolic NADH to FAD in the mitochondrial membrane, generating FADH2.

Mitochondrial Dysfunction: MERRF

• Myoclonic Epilepsy with Ragged Red Fibers (MERRF) is a mitochondrial disorder.
• It is maternally inherited and results in disruptions in the synthesis of proteins involved in oxidative phosphorylation.
• Clinical features may include; myoclonic seizures, hearing loss, lactic acidosis, exercise intolerance, and poor night vision.
• The results are due to accumulations of inactive mitochondria, leading to impaired ATP production.

ATP-ADP Translocation

• The ATP-ADP translocator facilitates the exchange of ATP and ADP across the inner mitochondrial membrane.
• ATP, in a net charge of -4, is exported from the matrix.
• ADP, with a net charge of -3, is imported into the matrix.
• This process involves Adenine nucleotide translocase as a carrier.
• Proton gradient drives the transport.

Role of Uncoupling Proteins

• Uncoupling protein 1 (UCP-1), primarily located in brown adipose tissue, allows protons (H+) to flow back into the mitochondrial matrix without passing through ATP synthase.
• The process utilizes these protons for heat production instead of ATP synthesis.

Reduction Potentials

• Reduction potential measures the tendency of a chemical species to acquire electrons.
• A higher reduction potential indicates a greater tendency for reduction.
• Reduction potentials are used to predict which species will act as electron donors and acceptors in chemical reactions.

Theoretical ATP Yield

• Electron transfer from NADH generates approximately 2.5 ATPs.
• Electron transfer from FADH2 generates approximately 1.5 ATPs.
• Glycolysis, pyruvate oxidation, and the citric acid cycle contribute to the overall ATP yield.
• The theoretical maximum ATP yield from glucose oxidation is 30-32 ATPs

Reactive Oxygen Species (ROS) Formation

• ROS are formed through homolytic cleavage, resulting in unpaired electrons.
• Key reactions for ROS formation include the Fenton and Haber-Weiss reactions.
• ROS can damage DNA, lipids, proteins, and enzymes, leading to various cellular effects.

Antioxidants

• Antioxidants neutralize the harmful effects of ROS.
• Enzymes such as superoxide dismutase, catalase, and peroxidase contribute to this process.
• Other antioxidants include vitamins C and E, buffering ions (like Fe and Cu), and specific proteins.

Nonshivering Thermogenesis

• Nonshivering thermogenesis is a metabolic process in warm-blooded animals.
• It generates heat by using energy from nutrient oxidation to release heat instead of converting to ATP.
• Uncoupling protein 1 (UCP-1) plays a crucial role in the process, found primarily in brown adipose tissue.
• Activation typically in response to cold environments.

Fructose Metabolism

• Fructose metabolism is primarily in the liver and muscle tissue.
• In muscles, fructose is phosphorylated into fructose-6-phosphate and enters glycolysis.
• In the liver, fructose is phosphorylated to fructose-1-phosphate.
• Fructose-1-phosphate is spilt into dihydroxyacetone phosphate and glyceraldehyde.
• Glyceraldehyde and dihydroxyacetone phosphate can enter glycolysis.

Test your knowledge on cellular respiration, ATP synthesis, and the biochemistry of mitochondria. This quiz covers key concepts including the roles of NADH, FADH2, and the proton gradient. Explore how energy is produced at the cellular level!