NAD+ Regeneration: Cellular Energy Production
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Uploaded by AmbitiousPreRaphaelites9938
Université Paris-Saclay
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Summary
This document explains the regeneration of NAD+ in both anaerobic and aerobic conditions. It details the processes of glycolysis, fermentation, and the electron transport chain. Two key shuttle systems, the glycerol-3-phosphate shuttle and the malate-aspartate shuttle, are also examined to understand how NADH is transported from the cytoplasm to the mitochondria and why these processes are crucial for cellular energy production.
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## Regeneration of NAD+ - **NAD+ regeneration in the cell:** - **Limited amount of NAD+ in the cell.** - **Glycolysis needs NAD+** to proceed. - **NADH is a product of glycolysis.** **NAD+ Regeneration in Anaerobic Conditions (Without Oxygen):** * **Glycolysis:** * **Glycerald...
## Regeneration of NAD+ - **NAD+ regeneration in the cell:** - **Limited amount of NAD+ in the cell.** - **Glycolysis needs NAD+** to proceed. - **NADH is a product of glycolysis.** **NAD+ Regeneration in Anaerobic Conditions (Without Oxygen):** * **Glycolysis:** * **Glyceraldehyde-3-phosphate dehydrogenase**: NAD+ is reduced to NADH and H+ * **1,3-bisphosphoglycerate (1,3 BPG)** is formed * **Fermentation Lactic in the Cytosol** * **Pyruvate** is converted to **lactate** by **lactate dehydrogenase**. * **NADH** is oxidized to **NAD+** * **NAD+ is regenerated for glycolysis to continue.** **NAD+ Regeneration in Aerobic Conditions (With Oxygen):** * **Oxidative decarboxylation of pyruvate (in the mitochondria):** * **Pyruvate dehydrogenase complex**: Pyruvate is converted to Acetyl-CoA, CO2, and NADH. * **The electron transport chain**: NADH is oxidized to NAD+ * **ATP is produced.** * **Lactate is not formed.** **NADH Transport from the Cytoplasm to the Mitochondria** * **The Electron Transport Chain:** NADH is oxidized to NAD+ in the mitochondria to generate ATP. * **Mitochondrial membrane is impermeable to NADH.** * **Two shuttle systems transport electrons from NADH in the cytoplasm to the electron transport chain in the mitochondria:** * **Glycerol-3-Phosphate Shuttle:** - NADH (in the cytoplasm) reduces **dihydroxyacetone phosphate** to **glycerol-3-phosphate**. - **Glycerol-3-phosphate** enters the mitochondrion. - **Glycerol-3-phosphate dehydrogenase** oxidizes it, using **FAD** to produce **FADH2** which donates electrons to the electron transport chain (complex II). - **Regenerates NAD+ in the cytoplasm.** * **Malate Aspartate Shuttle:** - **NADH in the cytoplasm**: Reduces **oxaloacetate** to **malate**. - **Malate** enters the mitochondrion. - **Malate dehydrogenase** oxidizes malate to **oxaloacetate,** regenerating **NAD+** in the cytoplasm, and reduces **NAD+** to **NADH** in the mitochondrion. - **Oxaloacetate** is converted to **aspartate** by **aspartate aminotransferase**. - **Aspartate** exits the mitochondrion. - **Aspartate** is converted back to **oxaloacetate** by **aspartate aminotransferase** in the cytosol. - **Oxaloacetate** is then converted back to **malate** by **NADH** to repeat the cycle. **Other Pathways for NAD+ Regeneration:** * **Fermentation:** * **Lactic acid fermentation:** Pyruvate is converted to lactate. * **Alcoholic fermentation:** Pyruvate is converted to ethanol. * **Oxidative decarboxylation of pyruvate:** pyruvate is oxidized to acetaldehyde in the presence of NAD+ **The Malate-Aspartate Shuttle Explained:** * The Malate-Aspartate shuttle is a major way to move reducing equivalents from the cytoplasm into the mitochondria for use in oxidative phosphorylation. * It is named after the two molecules involved in the process: malate and aspartate. * The shuttle works in two steps: 1. **In the cytoplasm:** - NADH reduces **oxaloacetate** to **malate** using **malate dehydrogenase** (cytoplasmic). - **Malate** is transported into the mitochondrial matrix. - **In the mitochondrial matrix:** - Malate is oxidized back to oxaloacetate by **malate dehydrogenase** (mitochondrial), generating **NADH** in the matrix that can enter the electron transport chain. - **Glutamate** donates an amino group to oxaloacetate, converting it to **aspartate**. - **Aspartate** translocates out of the mitochondrion in exchange for **glutamate.** - **Aspartate** is then re-converted to **oxaloacetate** in the cytoplasm by **aspartate aminotransferase**, regenerating **NAD+** in the cytoplasm. **Summary of NAD+ Regeneration:** - **Anaerobic conditions:** The regeneration of NAD+ is accomplished through fermentation - **Aerobic conditions:** The regeneration of NAD+ is accomplished primarily through the electron transport chain in the mitochondria via shuttles such as the malate-aspartate shuttle. - **Both pathways are important to maintain and sustain cellular energy production, particularly under differing oxygen conditions.**
