Cellular Respiration: Energy Flow

Energy Flow in Cellular Respiration

• Carbohydrates, lipids, and amino acids are key reduced fuels for cells
• Electrons from reduced fuels transfer to reduced cofactors NADH or FADH2
• The energy from NADH and FADH2 assists ATP production in oxidative phosphorylation

Chemiosmotic Theory

• ADP + Pi converts to ATP, while it is thermodynamically unfavorable
• Energy to phosphorylate ADP is from the flow of protons down the electrochemical gradient
• The energy from electron transport helps transport protons against the electrochemical gradient

Chemiosmotic Energy Coupling Requires Membranes

• ATP synthesis needs a proton gradient that can be established across an ion-impermeable membrane
• The Plasma membranes in bacteria can stably establish against ion-impermeable membranes
• The Inner membranes in mitochondria can stably establish against ion-impermeable membranes
• The Thylakoid membranes in chloroplasts can stably establish against ion-impermeable membranes
• Membranes must have proteins coupling the "downhill" electron flow in the electron-transfer chain with the "uphill" proton flow
• Membranes must have a protein coupling the "downhill" flow of protons to ADP phosphorylation

Mitochondrial Compartments

• The outer membrane, relatively porous, facilitates metabolite passage
• The intermembrane space has a similar environment to the cytosol but with a higher proton concentration and lower pH
• The inner membrane is relatively impermeable with a proton gradient, housing electron transport chain complexes and cristae for increased surface area
• The matrix, location of the citric acid cycle and parts of lipid and amino acid metabolism, maintains a lower proton concentration and higher pH

Electron Transport Chain

• The Electron Transport Chain ultimate function is generating electro-chemical potential use in ATP synthesis
• The series of electron carriers are flavin mononucleotide (FMN) or flavin adenine dinucleotide (FAD)
• Other electron carriers are cytochromes a, b, or c and iron-sulfur cluster

Electron Transfer and Reduction Potential

• The transfer order of electrons depends on reduction potential
• ΔG = -n F Δεo determines the change in free energy during electron transfer
• NADH + H+ +1/2 O2 converts to NAD+ + H2O
• ΔG = - 2×96500 × {0.817- (-0.32)} ≈ - 220 kJ/mol

ETC Co-Factors

• Key cofactors in the electron transport chain are:
  • FAD/FMN
  • NADH
  • Coenzyme Q
  • Porphyrin
  • Iron-sulfur clusters

NADH

• The TCA cycle and fatty acid β-oxidation fuel NAD+ reduction with electrons
• Only two electron can get uptaken or released at a time

FMN and FAD

• They can bind covalently to proteins, acting as funnels to distribute electrons
• Accepts two electrons from carriers unstable with single electrons
• Supplies the electrons to acceptors one at a time that can only accept single electrons

Cytochromes

• Cytochromes function as one-electron carriers
• Have Iron-coordinating porphyrin ring derivatives
• Differ by ring additions labeled as a, b, or c

Iron-Sulfur Clusters

• Iron-Sulfur Clusters work as one-electron carriers
• Coordination is achieved by cysteines in the protein
• They contain equal numbers of equal iron and sulfur atoms

Coenzyme Q (Ubiquinone)

• A lipid-soluble conjugated dicarbonyl compound, it readily accepts electrons
• Receiving two electrons, it combines two protons, becoming ubiquinol
• Diffusing freely in the membrane, ubiquinol transfers electrons alongside protons from a membrane side to another
• The mobile electron carrier moves electrons from Complexes I and II to Complex III

Mitochondrial Respiratory Chain

• Protein components of the mitochondrial respiratory chain include:
• NADH Dehydrogenase: mass of 850 kDa, 45 (14) subunits, FMN, Fe-S prosthetic groups
• Succinate Dehydrogenase : mass of 140 kDa, 4 subunits, FAD, Fe-S Prosthetic groups
• Ubiquinone: cytochrome c oxidoreductase: mass of 250 kDa, 11 subunits, Hemes, and Fe-S prosthetic groups
• Cytochrome c: mass of 13 kDa, 1 subunits, Prosthetic groups: Heme
• Cytochrome oxidase mass. of 204 kDa, 13 (3–4) subunits, Hemes; CuA, CuB Prosthetic groups

NADH: Ubiquinone Oxidoreductase (Complex I)

• A large assembly in the mammalian cell
• Over forty polypeptide chains, encoded by nuclear and mitochondrial genes
• The NADH binding site is on the matrix side
• Noncovalently bound flavin mononucleotide (FMN) accepts two electrons from NADH
• Multiple iron-sulfur centers move one electron at a time to the ubiquinone binding site.

Complex I Proton Pump:

• Transferring two electrons from NADH to ubiquinone includes proton transfer from the matrix (N) to the intermembrane space (P)
• Suggested four protons transport per one NADH which is NADH + Q + 5H+N = NAD+ + QH2 + 4 H+P
• Reduced coenzyme Q intakes two protons
• Proton wires are used in transporting protons from a series of amino that go through protonation and deprotonation for the net transfer of a proton

Complex I and Conformational Changes

Electron flow induces conformational changes by:

• Changing the redox state of the protein complex
• Altering transmembrane helices through long-range conformational changes
• Driving oxidation/reduction cycle of coenzyme Q, with quinone binding as key

Succinate Dehydrogenase (Complex II)

• FAD takes electron from succinate
• Iron-sulfur centers moves electrons one at a time, ubiquinone is turned into QH2
• There is no transport of protons
• Its A single enzyme acts as converts succinate to fumarate (citric acid cycle) and captures/donates electrons (electron transport chain)

Complex II Details

• Distance to travel for distance is is 40 Angstroms apart
• Fe-S cluster centers are less than 14 Angstroms part
• Highers the the closeness faster the the transfer rate
• 1 electron at a time is releasedfrom FADH2 to Fe-S to coenzyme Q
• 2 protons are released from Q from water

Ubiquinone: Cytochrome c Oxidoreductase, (Complex III)

• Uses two electrons from QH₂ to reduce two molecules of cytochrome c
• Additional elements are irion-sulfur clusters, cytochrome b, and cytochrome c
• Electron clearance from reduced quinones via the Q-cycle moves four additional protons to the intermembrane space

The Q Cycle

• The Q cycle follows, four protons transport across the membrane per two electrons that reach cyt c
• Then two of the four protons move come from oxidation the first incoming QH2
• For Electrons the pathway is to split twoards the P and N side
• The second molecule of QH₂ is oxidized, and releases releasing protons into the IMS. A molecule is reduced regeneration a QH2 that uptakes protons from matrix
• There is the net transfer of four protons per reduced coenzyme Q

Cytochrome C

• Ubiquinone moves through the membrane, while Cytochrome c moves through the intermembrane space, carrying single electrons from complex I to complex III
• This a heme-containing protein which carries a single electron from the cytochrome bc1 complex to cytochrome oxidase
• The heme iron is either ferrous (Fe3+, oxidized) or ferric (Fe2+, reduced)
• Note, the electron carier that transports a single is ancient protein and is highly conserved

Cytochrome Oxidase (Complex IV)

• This is a a membrane protein comes with 13 subunits in membranes of Mammals
• It Also comes with two heme groups a and a3, and copper ions
• The A: two ions that accept electrons from cyt c
• The B: bonded to heme a3, forming a binuclear center that transfers four electrons to oxygen

Cytochrome Oxidase Function

• Four electrons are released to lower oxygen molecular into a pair ofwater molecules
• Four protons are used from this processes released from the matrix
• Next is passing more from the matrix are going to the intermembrane

Summary of Electron Transport Chain

• For Complex I → Complex IV, 1NADH + 11H+(N) + 1/2O2 converts-> NAD+ + 10H+(P) + H2O
• For Complex II → Complex IV, FADH2 + 6H+(N) + 1/2O2 -> FAD + 6H+(P) + H2O
• The count of protons for transports are linked with ATP synthesization rates

Respirasome

• Multiple Complexes come together to associate in complex 1,3,4 with the complex 2 being freely for tca

ROS

• Reactive Oxygen Species (ROS) are created from the ETC
• The regulation here is mostly from substrate availability, so NADH AND ADP/PI
• Further their are inhibitors, for 1 that are meant to prevent hydrolysis of ATP
• Oxidative phosphorylation from this cascade

Chemiosmotic Model for ATP Synthesis

• Electron movement builds forces from protons(PMF)
• A Direct in how things happen that causes direct pumping, with H removal in Q and water forming
• Energy drives atp synthesization

Synthesization

• The P from the ph of the matrix helps transmembrane
• The pH the matrix contains at at 7.8 helps the the transmembrane and -7 and .15 of the P side
• It all causes the release of KJ into this

ATP synthesis

• In it all their is what is coupled with the electron transport
• P is what drives this by preventing halting of it all
• Next their the ones allow uncouplers that come the from the halts and atp
• All in that is atp for the end use

ATP

• Those functional in matrix of enzymes for hydro
• Transport of gradient
• Energy with phosphorylation used for adp

Explore energy flow in cellular respiration, focusing on the role of carbohydrates, lipids, and amino acids as reduced fuels. Learn how electrons from these fuels transfer to NADH and FADH2, and how this energy drives ATP production through oxidative phosphorylation and chemiosmotic energy coupling.