Citric Acid Cycle: Krebs Cycle/TCA cycle

• Energy metabolism begins with mastication and digestion, breaking down food, but no energy is extracted at this stage.
• Cells use organic compounds and enzymes to extract energy from chemical bonds to generate adenosine triphosphate (ATP).
• Energy-rich compounds proceed through three fundamental cycles: glycolytic, tricarboxylic acid (TCA), and oxidative phosphorylation.
• Glucose enters the glycolytic cycle, moves to the TCA cycle, and concludes with oxidative phosphorylation.
• ATP is produced, carbon dioxide (CO2) is released, and water (H2O) is formed throughout these energy cycle processes.
• These cycles provide a universal pathway for nutrients from various food sources, with nutrient proportions depending on animal type, diet, and physiological conditions.

Citric Acid Cycle

• The Citric Acid Cycle, or Krebs cycle/TCA cycle, is a vital metabolic pathway in cellular respiration.
• The Citric Acid Cycle is named after its founding compound, citrate, and Sir Hans Krebs.
• Krebs formulated its reactions into a cycle, occurring in the mitochondria
• The Citric Acid Cycle is essential for oxidizing acetyl residues (as acetyl-CoA) and reducing coenzymes.
• Coenzymes contribute to ATP synthesis, the cell's energy currency.
• Glucose, fatty acids, and most amino acids are metabolized into acetyl-CoA or cycle intermediates in the final common pathway for the aerobic oxidation of carbohydrates, lipids, and proteins.
• It plays a role in gluconeogenesis, lipogenesis, and amino acid interconversion.
• Oxygen (O2) is utilized, carbon dioxide (CO2) is produced as molecular intermediates are oxidized.
• ATP generation through oxidative phosphorylation requires electrons from NADH and FADH2, produced during the TCA cycle.
• Oxidation of one acetyl-CoA molecule yields three NADH and one FADH2.
• Oxidation of electron transport chain carriers yields 12 ATP: nine from NADH, two from FADH2, and one from substrate-level phosphorylation.
• The TCA cycle is regulated at three enzymatic steps by citrate synthase, isocitrate dehydrogenase, and a-ketoglutarate dehydrogenase.
• Enzyme activities are influenced by the cell's energy status.
• High ATP, NADH, and succinyl-CoA indicate a high energy state, inhibiting enzymes
• elevated ADP levels signal low energy, stimulating the cycle's operation.
• The citric acid cycle's primary function is to generate energy in ATP form.
• The TCA cycle is the final pathway for nutrient oxidation, metabolized into acetyl-CoA or cycle intermediates.
• The TCA cycle is an amphibolic process, serving both catabolic and anabolic functions.

Electron Transport System and Oxidative Phosphorylation

• Biological oxidation involves exothermic oxidation processes in living organisms, releasing energy.
• Energy transitions from higher to lower states, converting heat energy into chemical energy (ATP) via phosphorylation.
• Biological oxidation includes adding oxygen, removing hydrogen, or removing electrons.
• Redox reactions involve simultaneous oxidation and reduction facilitated by oxido-reductases, classified into five groups: oxidases, aerobic dehydrogenases, anaerobic dehydrogenases, hydro-peroxidases, and 5-oxygenases.
• Key coenzymes include flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD).

Electron Transport Chain

• The electron transport chain is a vital metabolic pathway where energy-rich molecules like glucose are oxidized to produce carbon dioxide and water.
• Reduced coenzymes, NADH and FADH2, donate electrons to the ETC, releasing energy to transport protons across the inner mitochondrial membrane, establishing a proton gradient that drives ATP synthesis from ADP and Pi.
• Coupling electron transport with ATP synthesis is oxidative phosphorylation.

Mitochondrial Structure

• The mitochondrion has an outer and specialized inner membrane separated by an intermembrane space.
• The outer membrane is permeable to various ions and small molecules, while the inner membrane is impermeable to most small ions and needs specialized transport systems for ion movement.
• The inner membrane is rich in proteins, with over half involved in oxidative phosphorylation.
• Inside the mitochondrion, the matrix contains enzymes for substrate oxidation, like pyruvate and fatty acids.
• The matrix hosts biochemical processes like the TCA cycle, alongside essential molecules like NAD+, FAD, ADP, and Pi, necessary for ATP production as well as mitochondrial DNA (mtDNA), RNA, and ribosomes.
• The inner mitochondrial membrane contains five protein complexes (I, II, III, IV, and V) that interact with mobile electron carriers like coenzyme Q and cytochrome c to facilitate electron transfer along the ETC.
• Electrons combine with oxygen and protons, forming water.
• Oxidative phosphorylation enables aerobic organisms to capture energy from respiratory substrates efficiently.
• Cyanide and carbon monoxide can inhibit oxidative phosphorylation.
• Transferring electrons from donors to acceptors releases energy for ATP formation through electron transport chains.
• The electron transport system and oxidative phosphorylation are vital for energy production in aerobic organisms, playing a crucial role in cellular respiration and metabolism.