Bioenergetics Flashcards

Bioenergetics

• Life is an energy-intensive process.

• Energy is required for muscle movement, cell creation, substance transport via blood, compound breakdown and synthesis, wound healing, and brain information processing.

Metabolism

• Metabolism is the sum of catabolism and anabolism.

• Catabolism:

  • Breakdown of larger molecules into smaller ones.

  • Oxidation and release of energy.

  • Involves nutrients and products of catabolism.

  • Produces energy and reducing agents for excretion.

  • Examples: Polysaccharides to Monosaccharides

• Anabolism:

  • Synthesis of small molecules into larger ones.

  • Requires energy.

  • Involves products of anabolism, including proteins and nucleic acids.

  • Example: Anabolism of proteins

Redox Reactions (Oxidation-Reduction)

• Oxidation:

  • Loss of electrons.

  • Example: Glucose loses electrons (and hydrogens).

• Reduction:

  • Gain of electrons. (gain e–)

  • Example: Oxygen gains electrons (and hydrogens).

• OIL RIG: Oxidation Is Loss, Reduction Is Gain.

• LeoGer: Loss of Electrons is Oxidation, Gain of Electrons is Reduction.

• Overall Reaction of Cellular Respiration (a Redox Reaction):

  • \C6H{12}O6 + 6O2 \rightarrow 6H2O + 6CO2 + ATP

  • Glucose is oxidized to carbon dioxide, and oxygen is reduced to water.

Mitochondria: The site of cellular Respiration

Outer Membrane:

• • Contains transport proteins for shuttling pyruvate into the mitochondrion.

• Inner Membrane:

  • Contains the Electron Transport Chain (ETC) and ATP synthase for oxidative phosphorylation.

• Cristae:

  • Highly folded to increase the surface area-to-volume ratio (SA:Vol ratio).

• Intermembrane Space:

  • Small space to quickly accumulate protons.

• Matrix:

  • Contains appropriate enzymes and a suitable pH for the Krebs cycle.

Adenosine Triphosphate (ATP)

• ATP is composed of:

  • Adenine

  • Ribose (together forming adenosine)

  • Three phosphate groups

• Contains 2 high-energy bonds (phosphoric anhydride bonds) and 1 phosphodiester bond.

• Hydrolysis of a phosphoric anhydride bond liberates more energy than hydrolysis of a phosphoric ester bond.

• The 3 phosphate groups (closest to furthest from the ribose sugar) are called alpha ($\alpha$), beta ($\beta$), and gamma ($\gamma$).

ATP Function

• Hydrolysis of the terminal phosphate (anhydride) of ATP produces ADP, phosphate ion, and 7.3 kcal/mol of energy.

• Hydrolysis of a phosphoric anhydride liberates more energy than hydrolysis of a phosphoric eater.

• ATP and ADP contain 2 high-energy phosphoric anhydride bonds.

• ATP is a universal carrier of phosphate groups.

• ATP is also a common currency for the storage and transfer of energy.

• The energy released by the breakdown (hydrolysis) of ATP is used to power many energy-requiring cellular reactions.

• \ATP + H2O \rightarrow ADP + H2PO_4^- + 7.3 kcal/mol

Common Catabolic Pathway

• The two parts of the Common Catabolic Pathway:

  • Citric Acid Cycle (also called the Tricarboxylic Acid Cycle (TCA) or Krebs cycle)

  • Electron Transport Chain Oxidative Phosphorylation/Chemiosmosis } Oxidative Phosphorylation

• Four principal compounds in the common catabolic pathway:

  • AMP, ADP, and ATP

  • NAD^+/NADH

  • FAD/FADH_2

  • Coenzyme A (CoA or CoA-SH)

NAD^+ (Nicotinamide Adenine Dinucleotide)

• A biological oxidizing agent, an electron acceptor that can oxidize other substances by accepting their electrons.

• Contains an AMP unit and a nicotinamide moiety linked by a glycosidic bond.

• The plus sign on NAD^+ represents the positive charge on the nitrogen.

NAD^+/NADH

• NAD^+ is a cofactor found in all living cells and exists in 2 forms:

  • NAD^+: a two-electron oxidizing agent and is reduced to NADH

  • NADH: a two-electron reducing agent that donates electrons and is oxidized to NAD^+

• NADH is an electron and hydrogen ion-transporting molecule.

• \NAD^+ + 2e^- + H^+ \rightleftharpoons NADH

• The reaction donates a hydride ion (H⁻), comprising two electrons and one proton, to NAD^+. This transfer reduces NAD^+ to NADH. The remaining proton (H^+$) from the substrate is released into the surrounding solution.

FAD/FADH_2

• FAD (Flavin adenine dinucleotide) is also a biological oxidizing agent.

• FAD is a two-electron oxidizing agent and is reduced to FADH_2

• FADH_2 is a two-electron reducing agent oxidized to FAD.

• FADH_2 is also a hydrogen ion-transporting molecule.

• FAD + 2H^+ + 2e^- \rightleftharpoons FADH_2

Coenzyme A (CoA)

• An acetyl-carrying group.

• Like NAD^+ and FAD, CoA contains a unit of ADP (Adenosine diphosphate).

• CoA is also written as CoA-SH to emphasize that it contains a Sulfhydryl group.

• The vitamin part of coenzyme A is pantothenic acid

• The acetyl group of acetyl CoA is bound as a high-energy thioester.

• Acetyl coenzyme A (An acyl CoA): CH_3-C(=O)-S-CoA

Intermediates in Chemical Reactions

• In Chemistry, an intermediate is a molecule or substance or compound formed from the reactants and reacts further to produce the final essential product(s).

• Most chemical reactions are stepwise (step by step) which take more than one basic or primary step to complete the entire process.

• In the process of converting biomolecules into several intermediates in the TCA Cycle, NADH & FADH_2 are formed.

• These 2 energy-rich molecules proceed to another series of chemical reactions in the Electron Transport Chain (ETC).

Glycolysis Overview

• Glycolysis occurs in the cytosol.

• Glycolysis in the Cytoplasm.

• Citric Acid Cycle in the Mitochondria

• Glucose is converted into pyruvate.

• Two molecules of ATP and two molecules of NADH are produced.

• Tricarboxyic Acid Cycle (TCA) refers to the 3 carboxyl group (-COOH) found in the first 2 intermediates of the cycle: • Citrate & • Isocitrate

• Pyruvate is transported into the mitochondrion.

• Pyruvate is converted to Acetyl CoA with the release of CO_2.

• Acetyl CoA enters the Citric Acid Cycle.

Glycolysis Stages

• Energy Investment Stage:

  • Glucose is phosphorylated and converted to fructose 6-phosphate, then phosphorylated again to fructose 1,6-bisphosphate.

  • Requires 2 ATP.

• Energy Harvesting Stage:

  • Fructose 1,6-bisphosphate is split into two 3-carbon molecules, which are converted to pyruvate.

  • Produces 4 ATP and 2 NADH.

• Net gain: 2 ATP, 2 NADH, and 2 pyruvate molecules.

Citric Acid Cycle and Electron Transport Chain

• The Citric Acid Cycle occurs in the mitochondria.

• Acetyl-CoA is oxidized to CO2, producing ATP, NADH, and FADH2.

• NADH and FADH_2 then donate electrons to the Electron Transport Chain.

• The electron transport chain pumps H+ ions into the intermembrane space that creates an electrochemical gradient.

• The gradient is then used by ATP synthase to produce ATP from ADP and inorganic phosphate.

Tricarboxylic Acid Cycle (TCA) notes

• Tricarboxylic Acid Cycle (TCA) refers to the 3 carboxyl groups (-COOH) found in the first 2 intermediates of the cycle:

  • Citrate

  • Isocitrate

• The overall reaction of the Tricarboxylic Acid Cycle is:

  • CH3C(=O)SCoA + GDP + Pi + 3 NAD^+ + FAD + 2H2O \rightarrow 2 CO2 + CoA + GTP + 3 NADH + FADH_2 + 3H^+

• Single Cycle:

  • 2 x CO_2

  • 1 x ATP

  • 1 x FADH_2

  • 3 x NADH + H^+

• Two Cycles:

  • 2x ATP

  • 2x FADH_2

  • 6 x NADH + H^+

Citric Acid Cycle Overview

• Overview: the 2-carbon acetyl group of acetyl CoA is fed into the cycle and two CO_2 are given off.

• There are 4 oxidation steps in the cycle.

• FAD \rightarrow FADH2, NAD^+ \rightarrow NADH, NAD^+ \rightarrow NADH, CO2, NAD^+ \rightarrow NADH, CO_2

Steps of the Citric Acid Cycle

• Step 1: Condensation of acetyl CoA with Oxaloacetate

  • The high-energy thioester of acetyl CoA is hydrolyzed.

  • This hydrolysis provides the energy to drive Step 1.

  • Citrate synthase, an allosteric enzyme, is inhibited by NADH, ATP, and succinyl-CoA.

• Step 2: Dehydration and rehydration, catalyzed by aconitase, gives isocitrate

  • Citrate and aconitate are achiral; neither has a stereocenter

• Step 3: Oxidation of isocitrate followed by decarboxylation gives α-ketoglutarate

  • Isocitrate dehydrogenase is an allosteric enzyme; it is inhibited by ATP and NADH, and activated by ADP and NAD^+.

• Step 4: Oxidative decarboxylation of α-ketoglutarate to succinyl-CoA

  • The two carbons of the acetyl group of acetyl CoA are still present in succinyl CoA

  • This multienzyme complex is inhibited by ATP, NADH, and succinyl CoA; it is activated by ADP and NAD^+

• Step 5: Formation of succinate

  • The two \CH_2-COO^- groups of succinate are now equivalent.

  • This is the first, and only, energy-yielding step of the cycle; a molecule of GTP is produced.

• Step 6: Oxidation of succinate to fumarate

• Step 7: Hydration of fumarate to L-malate

  • Malate is chiral and can exist as a pair of enantiomers; It is produced in the cycle as a single stereoisomer.

• Step 8: Oxidation of malate

  • Oxaloacetate now can react with acetyl CoA to start another round of the cycle by repeating Step 1.

Control of the Citric Acid Cycle

• Controlled by 3 feedback mechanisms

  • Citrate synthase: inhibited by ATP, NADH, and succinyl CoA; also product inhibition by citrate

  • Isocitrate dehydrogenase: activated by ADP and NAD^+, inhibited by ATP and NADH

  • α-Ketoglutarate dehydrogenase complex: inhibited by ATP, NADH, and succinyl CoA; activated by ADP and NAD^+

ATP production through the Citric Acid Cycle

• The citric acid cycle doesn’t produce much ATP directly.

• However, it can make a lot of ATP indirectly, by way of the NADH and FADH_2 it generates.

• These electron carriers, NADH and FADH_2, will connect with the last stage of cellular respiration, depositing their electrons into the ETC to drive synthesis of ATP molecules through oxidative phosphorylation.

• The TCA Cycle is a central driver of cellular respiration. It takes Acetyl-CoA produced by the oxidation of pyruvate and originally derived from glucose.

• The reduced electron carriers NADH and FADH_2 generated in the TCA cycle will pass their electrons into the ETC. Through oxidative phosphorylation, most of the ATP molecules produced in cellular respiration are generated.

ETC and Chemiosmosis: Oxidative Phosphorylation

• Electron Transport Chain (ETC): pathway that forms ATP as a result of the transfer of electrons from NADH & FADH2 to O2 by a series of electron acceptors

• ETC is powered by the movement of electrons through a series of electron acceptors (proteins) embedded in the inner membrane of the mitochondrion

• Oxidative Phosphorylation: made up of 2 closely connected processes: electron transport chain (ETC) and chemiosmosis

• In ETC, electrons from NADH & FADH_2 supercharge the protein complexes (I, III, and IV) and enable them to pump out H ions (H^+$) into the intermembrane space.

• energy released in these electron transfers is used to form a chemical gradient resulting in the synthesis of ATP proton gradient = difference in the concentrations of H ions (H^+$) or protons between the mitochondrial matrix and intermembrane space

Why Oxygen Is Needed

• Oxygen is needed so cells can use this molecule during oxidative phosphorylation, the final stage of cellular respiration.

• In the electron transport chain of Oxidative Phosphorylation, electrons are passed from one electron acceptor to another, and energy released in these electron transfers is used to form an electrochemical gradient.

• Oxygen sits at the end of the electron transport chain, where it accepts electrons and picks up protons to form water.

• If oxygen isn’t there to accept electrons, the electron transport chain will stop running, and ATP will no longer be produced by chemiosmosis.

• Without enough ATP, cells can’t carry out the reactions they need to function, and, after a long enough period of time, may even die.

Entry Points to the Electron Transport Chain

• All of the electrons that enter the ETC come from NADH and FADH_2, the 2 molecules produced during earlier stages of cellular respiration: glycolysis, pyruvate oxidation, and the citric acid cycle.

• NADH is very good at donating electrons in redox reactions (that is, its electrons are at a high energy level), so it can transfer its electrons directly to complex I, turning back into NAD^+.

• As electrons move through complex I in a series of redox reactions, energy is released, and the complex uses this energy to pump protons from the matrix into the intermembrane space.

• FADH_2 is not as good at donating electrons as NADH (that is, its electrons are at a lower energy level), so it cannot transfer its electrons to complex I. Instead, it feeds them into the transport chain through complex II, which does not pump protons across the membrane.

Key Players of the Electron Transport Chain

• Protein complexes I, II, III, and IV

• NADH & FADH_2 (2 electron carriers)

• Coenzyme Q

• Cytochrome C

• In a series of oxidation-reduction reactions, electrons from FADH2 and NADH are transferred from one complex to the next until they reach O2

• O2 is reduced to H2O

• As a result of electron transport, protons are pumped across the inner membrane to the intermembrane space.

• O2 + 4H^+ + 4e^- \rightarrow 2H2O + energy

Electron Transport Chain (ETC) & Oxidative Phosphorylation Process

• FMN receives the hydrogen from the NADH and 2 electrons. It also picks up a proton from the matrix. In this reduced form, it passes the electrons to iron-sulfur clusters that are part of the complex, and forces two protons into the intermembrane space.

• Complex: A structure consisting of a central atom, molecule, or protein weakly connected to surrounding atoms, molecules, or proteins.

• Ubiquinone: A lipid soluble substance that is a component of the electron transport chain and accepts electrons from complexes I and II.

Overview of Complexes in ETC process

• Complex I

  • This large complex contains several iron-sulfur (FeS) clusters, and coenzyme Q

  • Complex I oxidizes NADH to NAD^+

  • Some of the energy released in the oxidation of NAD^+ is used to move 2H+ from the matrix into the intermembrane space.

• Complex II

  • Complex II oxidizes FADH_2 to FAD

  • The energy released in this reaction is not sufficient to pump protons across the membrane.

• Complex III

  • Complex III delivers electrons from CoQH_2 to Cytochrome c (Cyt c)

  • Complex III has two channels through which the two H+ from each CoQH_2 oxidized are pumped from the matrix into the intermembrane space.

• Complex IV

  • electrons flow from Cyt c (oxidized) in Complex III to Cyt a3 in Complex IV

  • From Cyt a3 electrons are transferred to O_2

  • During this redox reaction, hydrogen ions (H^+$) are pumped from the matrix into the intermembrane space.

• Summing the reactions of Complexes I – IV: 6 H^+ are pumped out per NADH and four H^+ per FADH_2

Chemiosmotic Theory

• To explain how electron and H^+ transport produce the chemical energy of ATP, Peter Mitchell proposed the Chemiosmotic theory

• The energy-releasing oxidations give rise to proton pumping and a pH or proton gradient is created across the inner mitochondrial membrane.

• There is a higher concentration of H^+ in the intermembrane space than the mitochondrial matrix.

• This proton gradient provides the driving force to propel protons back into the mitochondrial matrix through the enzyme complex called proton translocating ATPase or ATP synthase.

Proton Pumps and ATP Synthase

• Complexes I, III, and IV of the ETC are proton pumps. As electrons move energetically downhill, the complexes capture the released energy and use it to pump H^+ ions from the matrix to the intermembrane space.

• This pumping of ions forms proton gradient between the mitochondrial matrix and the intermembrane space. The gradient is aka the proton-motive force.

• Like many other ions, protons can't pass directly through the phospholipid bilayer of the membrane because its core is too hydrophobic.

• H^+ ions can move down their concentration gradient only with the help of channel proteins that form hydrophilic channels across the membrane.

• $\Sigma$ In the inner mitochondrial membrane, H^+ ions have just 1 channel available: a membrane enzyme known as ATP synthase.

• $\Sigma$ Conceptually, ATP synthase is a lot like a turbine in a hydroelectric power plant. Instead of being turned by H_2O, it’s turned by the flow of H^+ ions moving down their chemical or proton gradient.

• $\Sigma$ As ATP synthase turns, it catalyzes the addition of a phosphate to ADP (phosphorylation) and form the ATP.

Protons and ATP Synthesis

• The protons (H^+$ ions) required to synthesize one ATP molecule via chemiosmosis in mitochondria is generally estimated to be approximately 3.7 to 4 H^+ ions per ATP.

• This estimate accounts for the protons needed to drive the ATP synthase enzyme and those required for transporting ATP, ADP, and Pi across the mitochondrial membranes. ATP synthase enzyme (F0F1-ATP synthase) utilizes the proton gradient across the inner mitochondrial membrane to drive the synthesis of ATP from ADP and Pi

• The number of protons translocated per ATP synthesized depends on the structure of the ATP synthase, particularly the number of c-subunits in the F_0 portion.

• In mammalian mitochondria, the c-ring typically consists of 8 subunits, leading to an estimate of about 2.7 H^+ ions required for ATP synthesis.

• However, additional H+ (protons) are consumed in transporting ATP out of the mitochondrion and importing ADP and phosphate into the matrix.

• This transport process is coupled with proton movement, adding approximately one more H^+ per ATP synthesized.

• Therefore, the total proton requirement per ATP molecule is approximately 3.7 to 4 H^+ ions.

• This proton-to-ATP ratio is crucial for understanding the efficiency of oxidative phosphorylation and the overall yield of ATP during cellular respiration.

Coupling of Oxidation and Phosphorylation

• Protons flow back into the matrix through channels in the F_0 unit of ATP synthase.

• The flow of protons is accompanied by formation of ATP in the F_1 unit of ATP synthase.

• ADP + Pi \rightarrow ATP + H2O

• The Functions of Oxygen Gas (molecular oxygen) are:

  • oxidize NADH to NAD^+ and FADH_2 to FAD so that these molecules can return to participate in the citric acid cycle

  • provide energy for the conversion of ADP to ATP

Chemiosmosis: The Energy-Coupling Mechanism

• ATP synthase is the enzyme that actually makes ATP

• ATP synthesis is driven by collapse of proton gradient

• Intermembrane space:

  • low pH = higher [H^+$]

• Mitochondrial matrix:

  • high pH = lower [H^+$]

Overall Reactions of Oxidative Phosphorylation

• The overall reactions of oxidative phosphorylation are:

• Oxidation of each NADH gives 3ATP.

• Oxidation of each FADH_2 gives 2 ATP.

• NADH + 3ADP + 1/2 O2 + 3Pi + H^+ \rightarrow NAD^+ + 3ATP + H_2O

• FADH2 + 2ADP + 1/2 O2 + 2Pi \rightarrow FAD + 2ATP + H2O

Energy Yield

• The Energy Yield A portion of the energy released during electron transport is now built into ATP.

• For each two-carbon acetyl unit entering the citric acid cycle, we get 3 NADH and 1 FADH_2.

• For each NADH oxidized to NAD^+, we get 3 ATP (1 NADH : 3 ATP)

• For each FADH2 oxidized to FAD, we get 2 ATP (1 FADH2 : 2 ATP)

• Thus, the yield of ATP per two-carbon acetyl group oxidized to CO2 is: 3 NADH 3 ATP NADH = 9 ATP 1 FADH2 2 ATP FADH_2 = 2 ATP 1 GTP = 1 ATP = 12 ATP

ATP Yield From Glucose Metabolism

• Site of Chemical Reaction

  • Cytosol

    • Glycolysis: Activation of glucose (4 – 2 = 2)

    • Phosphorylation: producing 2 NADH

    • Dephosphorylation: -> 2 pyruvate

  • Matrix of Mitochondria

    • Pyruvate Oxidation 2 pyruvate -> Acetyl-CoA

    • Producing 2 NADH

    • Citric Acid Cycle (2GTP = 2ATP)

  • Inner membrane of Mitochondrion

    • Oxidative Phosphorylation Producing 12 ATPs for each pyruvate

  • Total 36

Catabolic Pathways: Carbohydrate, Lipid, and Protein Metabolism

• Pathway refers to the sequence of steps that a chemical reaction undergoes from reactants to products. This includes:

  • the formation of intermediates and transition states

  • the associated energy changes throughout the process

  • the mechanism by which a reaction proceeds

  • the breaking and forming of chemical bonds

Catabolism of Biomolecules

• Catabolism or Breakdown of Biomolecules and their generated products for ATP production

  • Glucose --> Pyruvate through Glycolysis

  • Glycerol --> Dihydroxyacetone phosphate through Glycolysis

  • Fatty acid --> Acetyl CoA, NADH, FADH_2 through b-Oxidation

  • Protein --> Acetyl-CoA, Glucose, and Urea (excretion)

Glycolysis

• Glycolysis: a series of 10 enzyme-catalyzed reactions by which glucose is oxidized to 2 molecules of pyruvate

• During glycolysis, there is net conversion of 2ADP to 2ATP.

• \C6H{12}O6 \rightarrow 2 CH3 (=O)COO^- + 2 H^+

• \C6H{12}O6 + 2 ADP + 2 Pi \rightarrow 2 CH_3 (=O)COO^- + 2 ATP

Glycolysis Reactions Overview

• Reaction 1: Phosphorylation of α-D-glucose

  • A-D-Glucose-6-phosphate acts as a feedback inhibitor for hexokinase, preventing excessive phosphorylation of glucose.

• Reaction 2: Isomerization of glucose 6-phosphate to fructose 6-phosphate

• Reaction 3: Phosphorylation of fructose 6-phosphate

  • Phosphofructokinase is a key regulatory enzyme in glycolysis. Its activity increases when ATP levels are low to accelerate glycolysis.

• Reaction 4: Cleavage of fructose 1,6-bisphosphate to 2 triose phosphates

• Reaction 5: Isomerization of triose phosphates

• Reaction 6: Oxidation of -CHO group of D-glyceraldehyde 3-phosphate

• Reaction 7: transfer of a phosphate group from 1,3-bisphosphoglycerate to ADP

• Reaction 8: isomerization of 3-phosphoglycerate to 2-phosphoglycerate.

• Reaction 9: dehydration of 2-phosphoglycerate

• Reaction 10: phosphate transfer to ADP

Sum of Glycolysis Reactions

• Summing these 10 reactions gives the net equation for glycolysis:

• \C6H{12} O6 + 2 NAD^+ + 2 HPO4^{2-} + 2 ADP \rightarrow 2 CH3 (=O)COO^- + 2 NADH + 2 ATP + 2 H2O + 2 H^+

Pyruvate Metabolism

• Pyruvate is most commonly metabolized in one of three ways, depending on the type of organism and the presence or absence of O_2

  • Plants and animals use Aerobic conditions

    • Acetyl CoA Citric acid cycle

  • Contracting muscle uses anaerobic conditions

    • Lactate

  • Fermentation in yeast uses anaerobic conditions

    • Ethanol

Need for NAD+ and Regeneration

• A key to understanding the biochemical logic behind 2 of these reactions of pyruvate is to recognize that glycolysis needs a continuing supply of NAD^+

• If no oxygen is present to reoxidize NADH to NAD^+, then another way must be found to reoxidize it.

Anaerobic Conditions: Reduction of Pyruvate to Lactate

• In vertebrates under anaerobic conditions, the most important pathway for the regeneration of NAD^+ is reduction of pyruvate to lactate.

• Pyruvate, the oxidizing agent, is reduced to lactate.

• C6 H1 2 O6 Glucose 2 CH3 CHCOO- + 2 H+ OH Lactate lactate fermentation

High Levels of Lactate in Muscles

• While reduction to lactate allows glycolysis to continue, it increases the concentration of lactate and also of H^+ in muscle tissue

• When blood lactate reaches about 0.4 mg/100 mL, muscle tissue becomes almost completely exhausted.

Regeneration of NAD+ by Yeast

• Yeasts and several other organisms regenerate NAD^+ by this 2-step pathway:

  • decarboxylation of pyruvate to acetaldehyde

  • Acetaldehyde is then reduced to ethanol. NADH is the reducing agent. Acetaldehyde is reduced and is the oxidizing agent in this redox reaction.

Aerobic Conditions: Oxidative Decarboxylation of Pyruvate

• Under aerobic conditions, pyruvate undergoes oxidative decarboxylation

• The carboxylate group is converted to CO_2$$

• The remaining 2 carbons are converted to acetyl group of acetyl CoA
  Pyruvate CH3 CSCoA + CO2 + NADH O Acetyl-CoA oxidative decarboxylation CH3 CCOO- + NAD+ + CoASH O

ATP Produced from Glycolysis

• Step 1, 2, 3 Activation (glucose fructose 1,6-bisphosphate

• Step 5, 6, 9, 12 13 Oxidative phosphorylation (2 glyceraldehyde 3-phosphate 1,3-bisphosphoglycerate), produces 2NAD + + H+

• Step 1,6 Phosphate transfer to ADP from 1,3-bisphosphoglycerate and phosphoenolpyruvate

• Step 12 Oxidative decarboxylation 2 (pyruvate acetyl CoA), produces 2(NAD + + H+)

• Step 13 Oxidation to two acetyl CoA in the citric acid cycle etc.

Glycerol Enters Glycolysis

• Glycerol enters glycolysis via dihydroxyacetone phosphate.

• Glycerol is catabolized in the glycolysis pathway and yields 20 ATP molecules

Fatty Acids and Energy

• Fatty acids in triglycerides are the principal storage form of energy for most organisms.

• Hydrocarbon chains are a highly reduced form of carbon.

• The energy yield per gram of fatty acid oxidized is greater than that per gram of carbohydrate oxidized.

Beta-Oxidation of Fatty Acids

• b-Oxidation of Fatty Acids a series of 5 enzyme-catalyzed reactions that cleaves carbon atoms, 2 at a time from the carboxyl end of a fatty acid

• Reaction 1: the fatty acid is activated by conversion to an acyl CoA; activation is equivalent to the hydrolysis of 2 high-energy phosphate anhydrides.

• Reaction 2: oxidation of the α,b carbon-carbon single bond to a carbon-carbon double bond.

• Reaction 3: Hydration of the C=C double bond to give a 2° alcohol.

• Reaction 4: Oxidation of the 2°alcohol to a ketone.

• Reaction 5: cleavage of the carbon chain by a molecule of CoA-SH

Repetition and Unsaturated Fatty Acids

• This cycle of reactions is then repeated on the shortened fatty acyl chain and continues until the entire fatty acid chain is degraded to acetyl CoA.

• b-Oxidation of unsaturated fatty acids proceeds in the same way, with an extra step that isomerizes the cis double bond to a trans double bond.

Energy Yield from Beta-Oxidation

• Yield of ATP per mole of stearic acid (18 carbon)

Total ATP Produced from Fatty Acid Breakdown

• Before β-oxidation begins, the fatty acid is activated to form palmitoyl-CoA consuming 2 ATP equivalents

• Palmitic acid undergoes 7 cycles of β-oxidation, producing:

  • 7 NADH → 7 × 2.5 ATP = 17.5 ATP

  • 7 FADH₂ → 7 × 1.5 ATP = 10.5 ATP

  • 8 Acetyl-CoA (each cycle yields one, plus one from the final cleavage)

Additional Notes on Citric Acid Cycle

• Each of the 8 Acetyl-CoA molecules enters the TCA cycle, generating:

  • 3 NADH → 3 × 2.5 ATP = 7.5 ATP

  • 1 FADH₂ → 1 × 1.5 ATP = 1.5 ATP

  • 1 GTP → 1 ATP

Final ATP Calculation Examples Given

*Total ATP Calculation: Palmitic Fatty Acid (16 carbon)
** ATP from β-oxidation 17.5 (NADH) + 10.5 (FADH₂)… 28 ATP
** ATP from TCA cycle…………….. 80 ATP
** Subtotal…………………………….. 108 ATP
** Subtracting 2 ATP used in activation: 108 - 2 = 106 ATP

**ATP calculation for myristic fatty acid (14 carbon)
*** Acetyl-CoA………… 70 ATP
*** NADH…….…………. 15 ATP
*** FADH₂ …….……….. 9 ATP
*** Activation Cost…. - 2 ATP

*** Total Net ATP Yield: 92 ATP
**ATP Yield Calculation Of Myristic fatty acid (14 Carbon)

• Fixed Values
  *Variable Values

*Acetly CoA 8 = 80 ATP
Beta Oxidation Cycle = 7 = 28 ATP
Fatty Acid Activation Fixed Value = -2 ATP - 2 ATP Total Net 106 Atp

*Total ATP Calculation: Stearic Fatty Acid (18 carbon)

• 1. Beta oxidation Cycles. Each cycle produces:
  *Total from β-oxidation: 8 FADH₂ × 1.5 ATP = 12 ATP

• 8 NADH × 2.5 ATP = 20 ATP Total = 32 ATP

1. . Citric Acid Cycle (TCA Cycle) The 9 acetyl-CoA molecules enter the TCA cycle. Each acetyl-CoA yields:

• 3 NADH → 7.5 ATP

• . Beta
  1 FADH₂ → 1.5 ATP
  1 GTP → 1.0 ATP*2. . Activation of Stearic Acid (18 carbons) Before β-oxidation begins, stearic acid is activated to form stearoyl-CoA, a process that consumes 2 ATP equivalents. Stearic acid undergoes 8 cycles of β-oxidation (each cycle shortens the fatty acid chain by 2 carbons, and an 18-carbon chain yields 9 acetyl-CoA molecules).

Protein Catabolism

• Oxidative deamination the amino group of an amino acid is removed and an a-ketoacid is formed

• Deamination produces Ammonia which is toxic if accumulated. The liver converts ammonia to urea to be excreted in urine.

• Diets that are excessively high in proteins may overwhelm the kidneys with nitrogenous wastes and cause renal