Biological Oxidation-Reduction Reactions and Metabolic Pathway Regulation

13.4 Biological Oxidation-Reduction Reactions

Oxidation Levels of Carbon in Biomolecules

  • Most Oxidized Form of Carbon in Cells: Carbon is in its most oxidized state.

  • Most Reduced Form of Carbon in Cells: Carbon is in its most reduced state.

  • Definitions:

    • Oxidation (Catabolism): The process that releases energy.

    • Reduction (Anabolism): The process that requires energy.

Example of Biological Redox Reactions

  • Oxidation of Ferrous Ion by Cupric Ion:

    • Reaction: extFe2++extCu2+<br>ightleftharpoonsextFe3++extCu+ext{Fe}^{2+} + ext{Cu}^{2+} <br>ightleftharpoons ext{Fe}^{3+} + ext{Cu}^+

    • Two Half-Reactions:

    1. extFe2+<br>ightleftharpoonsextFe3++e−ext{Fe}^{2+} <br>ightleftharpoons ext{Fe}^{3+} + e^-

    2. extCu2++e−<br>ightleftharpoonsextCu+ext{Cu}^{2+} + e^- <br>ightleftharpoons ext{Cu}^+

    • Key Roles:

    • Fe²⁺: Oxidized (Electron Donor)

    • Cu²⁺: Reduced (Electron Acceptor)

    • Terms:

    • Reducing Agent: Electron-donating molecule (e.g., Fe²⁺)

    • Oxidizing Agent: Electron-accepting molecule (e.g., Cu²⁺)

    • Conjugate Redox Pair: A pair consisting of an electron donor and an acceptor.

Biological Redox Reaction Example

  • Reaction: extAcetaldehyde+extNADH+extH+<br>ightleftharpoonsextethanol+extNAD+ext{Acetaldehyde} + ext{NADH} + ext{H}^+ <br>ightleftharpoons ext{ethanol} + ext{NAD}^+

  • Half-Reactions:

    1. extAcetaldehyde+2extH++2e−<br>ightleftharpoonsextethanolext{Acetaldehyde} + 2 ext{H}^+ + 2e^- <br>ightleftharpoons ext{ethanol} (Reduction)

    2. extNADH+H+<br>ightleftharpoonsextNAD++2H++2e−ext{NADH} + H^+ <br>ightleftharpoons ext{NAD}^+ + 2H^+ + 2e^- (Oxidation)

  • Key Roles:

    • Acetaldehyde: Reduced (Electron Acceptor)

    • NADH: Oxidized (Electron Donor)

Biological Oxidations Generally Involve Dehydrogenation

  • Dehydrogenation: Reaction where a compound loses two electrons and two hydrogen ions; catalyzed by dehydrogenases.

  • Electrons can be transferred in various forms:

    • As electrons

    • As hydrogen atoms

    • As hydride ions (:H^-$)

    • Through direct combination with oxygen

  • In redox reactions, electrons move from metabolic intermediates to electron carriers and to acceptors with higher electron affinities, releasing energy.

Nernst Equation and Reduction Potentials

  • Reduction Potential (E): A measure of a molecule's affinity for electrons; higher values indicate greater affinity.

  • Equations:

    • ext{ΔE}°' = E°'( ext{e- acceptor}) - E°'( ext{e- donor})</p></li><li><p></p></li><li><p> ext{ΔG}°' = -nF ext{ΔE}°'

  • For a spontaneous reaction: ΔG must be negative, implying E(acceptor) > E(donor).

Hydrogen Electrode

  • Used for measuring standard reduction potential: 2 ext{H}^+ + 2e^-
    ightarrow ext{H}_2</p></li><li><p><strong>StandardPotential(E′º)</strong>:0volts</p></li><li><p>Utilizes:</p><ul><li><p>H2gasequilibratedatelectrodewith1MH+</p></li><li><p>Saltbridge(KClsolution)</p></li></ul></li></ul><h4id="0bf54fe3−b17d−4f6c−82c7−32781f7452f0"data−toc−id="0bf54fe3−b17d−4f6c−82c7−32781f7452f0"collapsed="false"seolevelmigrated="true">StandardReductionPotentialsofImportantHalf−Reactions</h4><ul><li><p><strong>Table13−7a</strong>:Includeshalf−reactionswiththeirrespectivestandardreductionpotentials(</p></li><li><p><strong>Standard Potential (E'º)</strong>: 0 volts</p></li><li><p>Utilizes:</p><ul><li><p>H₂ gas equilibrated at electrode with 1 M H⁺</p></li><li><p>Salt bridge (KCl solution)</p></li></ul></li></ul><h4 id="0bf54fe3-b17d-4f6c-82c7-32781f7452f0" data-toc-id="0bf54fe3-b17d-4f6c-82c7-32781f7452f0" collapsed="false" seolevelmigrated="true">Standard Reduction Potentials of Important Half-Reactions</h4><ul><li><p><strong>Table 13-7a</strong>: Includes half-reactions with their respective standard reduction potentials (E'ºinvolts).</p><ul><li><p>Displaysvalueslike:</p></li><li><p>in volts).</p><ul><li><p>Displays values like:</p></li><li><p> rac{1}{2} ext{O}2 + 2 ext{H}^+ + 2e^- ightarrow ext{H}2 ext{O} ext{ (0.816 V)}</p></li><li><p></p></li><li><p> ext{Fe}^{3+} + e^-
    ightarrow ext{Fe}^{2+} ext{ (0.771 V)}</p></li><li><p>Negativevaluessuggestweakeroxidizingagents.</p></li></ul></li></ul><h4id="e3c61954−8530−4897−860b−024d336e6ed3"data−toc−id="e3c61954−8530−4897−860b−024d336e6ed3"collapsed="false"seolevelmigrated="true">AcetaldehydeReductionExample</h4><ul><li><p><strong>ExampleReactions</strong>:</p><ul><li><p></p></li><li><p>Negative values suggest weaker oxidizing agents.</p></li></ul></li></ul><h4 id="e3c61954-8530-4897-860b-024d336e6ed3" data-toc-id="e3c61954-8530-4897-860b-024d336e6ed3" collapsed="false" seolevelmigrated="true">Acetaldehyde Reduction Example</h4><ul><li><p><strong>Example Reactions</strong>:</p><ul><li><p> ext{NAD}^+ + ext{H}^+ + 2e^-
    ightarrow ext{NADH} + H^+ ext{ (E'º = -0.320 V)}</p></li><li><p>Equivalenttorequiringareversalofsignifreactiondirectionchanges.</p></li></ul></li></ul><h4id="e122f2e6−e8e9−47e1−b2eb−83144c662406"data−toc−id="e122f2e6−e8e9−47e1−b2eb−83144c662406"collapsed="false"seolevelmigrated="true">SampleProblem:CalculatingStandardFree−EnergyChangeΔG’°</h4><ol><li><p>Forthereaction:</p></li><li><p>Equivalent to requiring a reversal of sign if reaction direction changes.</p></li></ul></li></ul><h4 id="e122f2e6-e8e9-47e1-b2eb-83144c662406" data-toc-id="e122f2e6-e8e9-47e1-b2eb-83144c662406" collapsed="false" seolevelmigrated="true">Sample Problem: Calculating Standard Free-Energy Change ΔG’°</h4><ol><li><p>For the reaction: ext{Acetaldehyde} + ext{NADH} + ext{H}^+ ightarrow ext{ethanol} + ext{NAD}^+</p><ul><li><p>Half−reactionsandcorresponding</p><ul><li><p>Half-reactions and correspondingE'°:</p><ul><li><p>1::</p><ul><li><p>1: ext{E'° = -0.197 V}</p></li><li><p>2:</p></li><li><p>2: ext{E'° = -0.320 V}</p></li></ul></li></ul></li><li><p>ActualFreeEnergyChange</p></li></ul></li></ul></li><li><p>Actual Free Energy Change ext{ΔG}when[acetaldehyde]=[NADH]=2.5M,[ethanol]=[NAD+]=0.1M.</p></li></ol><h4id="5c4d4fa9−c1b9−46c5−8786−9606dc39ab18"data−toc−id="5c4d4fa9−c1b9−46c5−8786−9606dc39ab18"collapsed="false"seolevelmigrated="true">NADandNADPasCommonRedoxCofactors</h4><ul><li><p><strong>PyridineNucleotides</strong>:NADandNADPcandissociatefromenzymesafterareaction.</p></li><li><p><strong>NAD+</strong>to<strong>NADH</strong>:CommonlyinvolvestransferringhydridefromalcoholtoNAD+.</p></li></ul><h4id="2f5bc994−8971−4b1d−952c−3aac2caef6fa"data−toc−id="2f5bc994−8971−4b1d−952c−3aac2caef6fa"collapsed="false"seolevelmigrated="true">ReducingEquivalent</h4><ul><li><p><strong>Definition</strong>:Asingleelectronequivalentparticipatinginanoxidation−reductionreaction,regardlessofthetransfermethod.</p></li></ul><h4id="0d9d225b−f82f−4b8f−a023−3ba47c487445"data−toc−id="0d9d225b−f82f−4b8f−a023−3ba47c487445"collapsed="false"seolevelmigrated="true">FlavinCofactors</h4><ul><li><p>Allowsingleelectrontransfersandpermittheuseofmolecularoxygenasanultimateelectronacceptor.</p></li><li><p>Flavins:Tightlyboundtoproteins,canvaryinreductionpotential,andhaveavitaminsourceofriboflavin.</p></li></ul><h3id="924fdb88−54b2−41b1−9008−18bbcad40b38"data−toc−id="924fdb88−54b2−41b1−9008−18bbcad40b38"collapsed="false"seolevelmigrated="true">13.5RegulationofMetabolicPathways</h3><h4id="81b68245−21bf−4c65−9282−6a6138022601"data−toc−id="81b68245−21bf−4c65−9282−6a6138022601"collapsed="false"seolevelmigrated="true">IntroductiontoMetabolicPathways</h4><ul><li><p><strong>MetabolicPathways</strong>:Connectedandaffecteachother(e.g.,glycanbiosynthesis,lipidmetabolism,energymetabolism).</p></li></ul><h4id="5597cbd4−614a−4ebd−b574−2096abd4777b"data−toc−id="5597cbd4−614a−4ebd−b574−2096abd4777b"collapsed="false"seolevelmigrated="true">CellsandOrganismsMaintainDynamicSteadyState</h4><ul><li><p>Inametabolicallyactivecell,intermediatesareconsumedandformedatequalrates,maintainingconstant[S]withfluxratewhen [acetaldehyde] = [NADH] = 2.5 M, [ethanol] = [NAD+] = 0.1 M.</p></li></ol><h4 id="5c4d4fa9-c1b9-46c5-8786-9606dc39ab18" data-toc-id="5c4d4fa9-c1b9-46c5-8786-9606dc39ab18" collapsed="false" seolevelmigrated="true">NAD and NADP as Common Redox Cofactors</h4><ul><li><p><strong>Pyridine Nucleotides</strong>: NAD and NADP can dissociate from enzymes after a reaction.</p></li><li><p><strong>NAD+</strong> to <strong>NADH</strong>: Commonly involves transferring hydride from alcohol to NAD+.</p></li></ul><h4 id="2f5bc994-8971-4b1d-952c-3aac2caef6fa" data-toc-id="2f5bc994-8971-4b1d-952c-3aac2caef6fa" collapsed="false" seolevelmigrated="true">Reducing Equivalent</h4><ul><li><p><strong>Definition</strong>: A single electron equivalent participating in an oxidation-reduction reaction, regardless of the transfer method.</p></li></ul><h4 id="0d9d225b-f82f-4b8f-a023-3ba47c487445" data-toc-id="0d9d225b-f82f-4b8f-a023-3ba47c487445" collapsed="false" seolevelmigrated="true">Flavin Cofactors</h4><ul><li><p>Allow single electron transfers and permit the use of molecular oxygen as an ultimate electron acceptor.</p></li><li><p>Flavins: Tightly bound to proteins, can vary in reduction potential, and have a vitamin source of riboflavin.</p></li></ul><h3 id="924fdb88-54b2-41b1-9008-18bbcad40b38" data-toc-id="924fdb88-54b2-41b1-9008-18bbcad40b38" collapsed="false" seolevelmigrated="true">13.5 Regulation of Metabolic Pathways</h3><h4 id="81b68245-21bf-4c65-9282-6a6138022601" data-toc-id="81b68245-21bf-4c65-9282-6a6138022601" collapsed="false" seolevelmigrated="true">Introduction to Metabolic Pathways</h4><ul><li><p><strong>Metabolic Pathways</strong>: Connected and affect each other (e.g., glycan biosynthesis, lipid metabolism, energy metabolism).</p></li></ul><h4 id="5597cbd4-614a-4ebd-b574-2096abd4777b" data-toc-id="5597cbd4-614a-4ebd-b574-2096abd4777b" collapsed="false" seolevelmigrated="true">Cells and Organisms Maintain Dynamic Steady State</h4><ul><li><p>In a metabolically active cell, intermediates are consumed and formed at equal rates, maintaining constant [S] with flux ratev1 = v2$$.

Regulation of Enzyme Amount and Activity

  • Flux Modulation: Can change number of enzyme molecules or catalytic activity of existing enzymes.

  • Time scales can vary from less than a millisecond to several days.

Factors Affecting Enzyme Activity

  • 1. Extracellular Signals: Hormonal, neuronal signals, growth factors.

  • 2. Transcription Factors: Bind specific DNA regions to modulate gene expression.

  • 3. mRNA Degradation: Stability varies based on resistance to degradation.

  • 4. mRNA Translation: Regulated rates affect protein synthesis.

  • 5. Protein Degradation: A short half-life can help proteins reach new steady states faster.

Example Average Half-Life of Proteins in Mammalian Tissues

Tissue

Average Half-Life (days)

Liver

0.9

Kidney

1.7

Heart

4.1

Brain

4.6

Muscle

10.7

Enzyme Sequestration

  • Sequestering enzymes in different compartments reduces their activity.

Impact of Transcriptome on Proteome

  • Changes in the transcriptome can lead to changes in the proteome, affecting the metabolome (balance of metabolites).

  • Transcriptome: Complete set of mRNAs.

  • Proteome: Complete set of proteins.

  • Metabolome: Complete set of low molecular weight metabolites.

Enzymes and Substrate Concentration

  • Michaelis-Menten Kinetics: Enzyme activity sensitive to substrate concentration.

  • When [S] << Km, reaction rate depends linearly on [S].

Allosteric Effectors

  • Allosteric change can convert hyperbolic kinetics to sigmoid kinetics based on substrate concentration, characterized by a Hill coefficient.

Covalent Modifications and Regulatory Proteins

  • Covalent modifications like phosphorylation can rapidly occur upon regulatory signals, altering enzyme activities.