THE KREBS CYCLE (Citric Acid Cycle).pptx

The Krebs cycle is a central metabolic pathway in cellular respiration that occurs in the mitochondrial matrix of eukaryotes (and the cytoplasm of prokaryotes). It functions as a cyclic series of enzymatic reactions that oxidizes acetyl-CoA (derived from carbohydrates, fats, and proteins) to carbon dioxide (CO₂) while generating high-energy electron carriers (NADH, FADH₂) and ATP (or GTP).

1. The Kreb’s cycle( citric acid cycle)

2. INTRODUCTION The Krebs cycle, also called the citric acid cycle or TCA cycle, is a series of chemical reactions in the mitochondria.It is the central pathway of energy production in cells.Breaks down acetyl-CoA (from carbohydrates, fats, proteins) into CO₂.Produces NADH and FADH₂, which fuel the electron transport chain to make ATP.Provides building blocks for amino acids, fatty acids, and other biomolecules.

3. Brief History on the Kreb’s cycle The cycle was discovered in 1937 by Sir Hans Adolf Krebs, a German-born British biochemist.
He proposed the cycle as the main pathway for cellular respiration.
Krebs received the Nobel Prize in Physiology or Medicine in 1953 for this discovery.
The cycle is also known as the citric acid cycle (first product formed) or the tricarboxylic acid (TCA) cycle.

4. Location of the Krebs Cycle The Krebs cycle takes place in the mitochondrial matrix, the innermost compartment of the mitochondria.
Mitochondria are known as the “powerhouse of the cell” because they are the main site of energy production.
The mitochondrion has a double-membrane structure:
Outer membrane: smooth and permeable to small molecules.
Inner membrane: highly folded into cristae, housing the electron transport chain.
The matrix contains the enzymes that drive the Krebs cycle.
This location is important because it keeps the cycle close to the electron transport chain (ETC) in the inner mitochondrial membrane, where NADH and FADH₂ (produced in the cycle) are used to generate ATP.

5. Overview of Cellular Respiration What is Cellular Respiration? Cellular respiration is the process by which cells break down nutrients (mainly glucose, but also fats and proteins) to release energy in the form of ATP (adenosine triphosphate).It is essential for all living cells, as ATP powers activities such as: Muscle contraction, Active transport of molecules across membranes, Biosynthesis of proteins, nucleic acids, and lipids. Overall reaction of cellular respiration : C6H{12}O6 + 6 O2 《——》6 CO2 + 6 H2O + energy {~36–38 ATP} Cellular respiration has three major stages: Glycolysis (in the cytoplasm) Krebs cycle / Citric Acid Cycle (in the mitochondrial matrix) Electron Transport Chain (ETC) & Oxidative Phosphorylation (in the inner mitochondrial membrane)

6. Role of Each Stage Glycolysis Occurs in the cytoplasm. Breaks 1 glucose (6C) into 2 pyruvate (3C).Produces 2 ATP (net gain) and 2 NADH. Anaerobic process (does not require oxygen). 2. Krebs Cycle (Citric Acid Cycle)Occurs in the mitochondrial matrix. Each pyruvate is converted to acetyl-CoA before entering. Produces 2 ATP (or GTP), 6 NADH, 2 FADH₂, and 4 CO₂ per glucose molecule. Aerobic (requires oxygen indirectly). 3. Electron Transport Chain (ETC) & Oxidative Phosphorylation Located in the inner mitochondrial membrane. Uses NADH and FADH₂ from glycolysis and the Krebs cycle. Produces the majority of ATP (~32–34 ATP).Final electron acceptor is oxygen (O₂), forming water (H₂O).

7. Why the Krebs Cycle is Central The Krebs cycle acts as the hub of metabolism because:
It connects the breakdown of carbohydrates, fats, and proteins.
Produces high-energy molecules (NADH, FADH₂) needed for ATP synthesis.
Releases carbon dioxide, which we exhale.
Provides intermediates for biosynthetic pathways (amino acids, fatty acids, nucleotides). Without the Krebs cycle: Cells would not efficiently extract energy from nutrients. Electron transport chain would not have fuel (NADH/FADH₂).Biosynthesis of essential compounds would be impaired.

8. Input to the Krebs Cycle The main input to the Krebs cycle is Acetyl-CoA (2-carbon molecule). Acetyl-CoA is formed from the breakdown of: 1. Carbohydrates :
Glucose undergoes glycolysis → produces pyruvate.
Pyruvate is transported into mitochondria.
Pyruvate is converted into Acetyl-CoA by the enzyme pyruvate dehydrogenase (releasing CO₂ and NADH). 2. Fats (Lipids): Fatty acids undergo β-oxidation → directly generate Acetyl-CoA.

9. 3. Proteins (Amino Acids): Certain amino acids are broken down into intermediates that convert into Acetyl-CoA.
Once formed, Acetyl-CoA combines with oxaloacetate (4C) to form citrate (6C), starting the cycle.
Oxygen is indirectly required because NADH and FADH₂ produced must be oxidized in the Electron Transport Chain (ETC) to keep the cycle running. Input to the Krebs Cycle cont..

10. Steps of the Krebs cycle Step 1: Formation of Citrate The cycle begins when Acetyl-CoA (2C) combines with Oxaloacetate (4C) → forms Citrate (6C). Enzyme : Citrate Synthase. This is an irreversible and highly regulated step, ensuring that acetyl-CoA enters the cycle. Reaction: Acetyl-CoA + Oxaloacetate + H2O  Citrate + CoA-SH

11. Step 2: Isomerization of Citrate to Isocitrate Citrate (6C) is rearranged to form Isocitrate (6C).
Enzyme: Aconitase .
Process involves two steps:
1. Citrate → cis- aconitate (intermediate).
2. cis- aconitate → isocitrate . No energy is produced; this step just prepares citrate for oxidation.

12. Step 3: Oxidative Decarboxylation of Isocitrate Isocitrate (6C) is oxidized and decarboxylated → forms α- Ketoglutarate (5C). Enzyme : Isocitrate Dehydrogenase. Products :1 NADH1 CO₂ (waste product, exhaled).This is a rate-limiting step in the cycle. Step 4: Oxidative Decarboxylation of α- Ketoglutarate α- Ketoglutarate (5C) is converted into Succinyl -CoA (4C). Enzyme : α- Ketoglutarate Dehydrogenase Complex (similar to pyruvate dehydrogenase). Products :1 NADH1 CO₂ (released).This step removes another carbon and produces energy carriers.

13. Step 5: Substrate-Level Phosphorylation Succinyl -CoA (4C) is converted to Succinate (4C). Enzyme : Succinyl -CoA Synthetase (Succinate Thiokinase ). Products :1 ATP (or GTP) by substrate-level phosphorylation.CoA -SH is released. This is the only step in the cycle that directly produces ATP (or GTP). Step 6: Oxidation of Succinate Succinate (4C) is oxidized to Fumarate (4C). Enzyme : Succinate Dehydrogenase (embedded in the inner mitochondrial membrane, also part of ETC Complex II). Product : 1 FADH₂ (enters electron transport chain).

14. Step 7: Hydration of Fumarate Fumarate (4C) is hydrated to form Malate (4C). Enzyme : Fumarase.Simply involves the addition of water (H₂O). No energy molecules are produced in this step. Step 8: Regeneration of Oxaloacetate Malate (4C) is oxidized back into Oxaloacetate (4C). Enzyme : Malate Dehydrogenase. Product : 1 NADH.
Oxaloacetate is regenerated, allowing the cycle to repeat.

15. Conclusion “In the final step, malate is oxidized to regenerate oxaloacetate, catalyzed by malate dehydrogenase. One NADH is produced. This completes the cycle and regenerates the starting molecule, oxaloacetate, so that another acetyl-CoA can enter the cycle.”