Cellular Respiration and TCA Cycle

Aerobic Metabolism: TCA Cycle and Oxidative Phosphorylation

• The TCA cycle, also known as the Krebs cycle, Citric acid cycle, or Tricarboxylic acid cycle, is a key process in aerobic metabolism.
• The TCA cycle is a common terminal pathway for the catabolism of sugars, fats, and amino acids.
• The TCA cycle occurs in the mitochondrial matrix of all tissues with mitochondria, except for red blood cells and white muscle fibers.

TCA Cycle Reactions

• The TCA cycle consists of 8 enzyme-catalyzed reactions that convert acetyl-CoA into CO2.
• The reactions involve the conversion of acetyl-CoA to citrate, isocitrate, α-ketoglutarate, succinyl-CoA, succinate, fumarate, malate, and oxaloacetate.
• The TCA cycle produces NADH and FADH2 as reduced cofactors, which are essential for energy trapping and biosynthesis.

Energy Yield of TCA Cycle

• The TCA cycle produces 3 NADH and 1 FADH2, which result in a net gain of 12 ATP through oxidative phosphorylation.
• The TCA cycle also produces 1 GTP, which is equivalent to 1 ATP.

Electron Transport Chain and Oxidative Phosphorylation

• The electron transport chain is a series of electron carriers with increasing electron affinity and decreasing redox potential.
• The electron transport chain is located in the inner mitochondrial membrane.
• Oxidative phosphorylation occurs when the electrons from NADH and FADH2 are passed through the electron transport chain, resulting in the synthesis of ATP from ADP and Pi.

Irreversibility of Key Stages

• Three enzyme steps in the TCA cycle are highly exergonic and irreversible: citrate synthase, isocitrate dehydrogenase, and α-ketoglutarate dehydrogenase.### Electron Transport Chain

• The electron transport chain is a process of transferring H atoms to oxygen, located in the mitochondria, and occurs in most tissues and cell types, except for red blood cells.

• The function of the electron transport chain is to trap energy and directly phosphorylate ADP to produce ATP.

Mitochondrial Compartments

• Oxidative phosphorylation takes place in association with the inner compartments of the mitochondria.
• The components of the electron transport chain are "buried" in the inner mitochondrial membrane.

NADH and NAD+

• NADH is the reduced form of nicotinamide adenine dinucleotide, with 2H atoms.
• NAD+ is the oxidized form of nicotinamide adenine dinucleotide.

Stepwise Transfer of H Atoms to O2

• The stepwise transfer of H atoms to O2 involves the transfer of 2H atoms from NADH to O2, resulting in the formation of H2O.

Components of the Electron Transport Chain

• H pair acceptors: Flavin cofactors, Coenzyme Q (CoQ).
• Electron acceptors: Iron sulphur proteins, Cytochrome proteins.

The Electron Transport Chain

• The electron transport chain consists of complexes I, III, and IV, which pump protons across the membrane, creating a proton and an electrochemical gradient.
• The energy of the proton gradient is used for the synthesis of ATP from ADP by the F0, F1- ATP synthase.

ATP Synthesis

• The mechanism of ATP synthesis involves the transfer of electrons from the electron transport chain to ATP synthase, resulting in the formation of ATP from ADP and Pi.

Control of Electron Transport

• The rate of electron transport is controlled by the levels of ADP and ATP, described as respiratory control, or 'tightly-coupled' oxidative phosphorylation.
• Increased [ADP] increases the rate of O2 uptake, while increased [ATP] decreases O2 uptake.

Inhibitors and Uncouplers

• Inhibitors of oxidative phosphorylation: CN-, rotenone, CO.
• Uncouplers of oxidative phosphorylation: dinitrophenol (DNP), thermogenin protein in brown adipose tissue.

ATP Production

• The complete oxidation of 1 molecule of glucose results in the production of 32 or 30 x ATP.
• The ATP yield from NADH reoxidation is 2.5 ATP, and from FADH2 reoxidation is 1.5 ATP.