Energy Metabolism in Muscle

SGD 24-25 August 2009, Year 1 Medicine, Musculoskeletal Block
SGD 23-24 October 2013, Year 1 Medicine, Musculoskeletal Block


Topics covered:

1. Energy sources for muscle contraction
2. Aerobic and anaerobic pathways for energy production in muscle cells
3. # of ATP produced in glucose catabolism
4. Reactions of glycolysis that use or produce energy (2 ATP-utilizing reactions & 3 energy-producing reactions - 2 NADH, 2 ATP, 2 ATP)
5. Severe muscular exercise and plasma lactate level increase
6. Cori cycle and its importance in muscle metabolism
7. Glucose-alanine cycle and its importance in muscle metabolism
8. Reactions of beta-oxidation that use or produce energy (1 ATP-utilising reaction & 2 energy-producing reactions - 1 FADH2, 1 NADH)
9. Products of 1 cycle of beta-oxidation
10. # of ATP produced by oxidation of each NADH and FADH2 in ETC
11. Calculation of net ATP produced from oxidation of 1 palmitic acid (C16:0)
12. Citric acid cycle (Krebs cycle or TCA cycle) - where it occurs and # of energy-producing substances formed (mitochondrial matrix; 3 NADH, 1 FADH2, 1 GTP)
13. Why TCA cycle is an amphibolic pathway (catabolic - oxidation of acetyl CoA, anabolic - TCA intermediates used for biochemical anabolic pathways)
14. Why TCA cycle is an aerobic pathway
15. Chemiosmotic theory of oxidative phosphorylation
16. Inhibitors and uncouplers of ETC
17. Why impairment of ETC causes lactic acidosis

Inhibitors of ETC and DNA mutations lead to reduced activity of ETC

When the respiratory chain is blocked, pyruvate accumulates outside the mitochondria, and when too much pyruvate has accumulated, the cells start to convert it to lactic acid. Many patients with mitochondrial disease have lactic acidosis.

Inhibitors of ETC & DNA mutations cause increased NADH --> increased NADH/NAD+ ratio --> inhibition of PDH --> pyruvate cannot be converted to acetyl CoA --> conversion of pyruvate to lactate --> lactic acidosis

Mitochondrial DNA (mtDNA) encodes 13 subunits of ETC complexes
Nuclear DNA (nDNA) encodes >70 subunits of proteins in oxidative phosphorylation

Cori cycle

The Cori cycle involves the utilization of lactate which is produced by anaerobic glycolysis in non-hepatic tissues such as myocytes (muscle cells) and erythrocytes (red blood cells) as carbon source for hepatic gluconeogenesis. Liver then converts the lactate back into glucose for use by non-hepatic tissues. The gluconeogenic part of Cori cycle utilizes ATP (net consumer of energy, uses an extra 4 ATP) and the Cori cycle canot be sustained indefinitely.

Elimination of nitrogenous wastes

Why does the body make nitrogenous wastes? How does the body process nitrogenous wastes? The body processes nitrogenous wastes in 4 ways - 1) Glutamine, 2) Transamination, 3) Deamination, and 4) Urea. What is the role of glutamine in nitrogenous waste transport? Transamination is converting one amino acid to another. Deamination is removing the amine from an amino acid. Example of transamination and deamination is the glucose-alanine cycle. Urea synthesis occurs in the liver.

Cellular respiration

Cellular respiration is the process in which an organism breaks down fuel (glucose, glycogen, protein, lipids) to capture energy in a usable form (ATP).

Phosphorylation and dephosphorylation

When a phosphate (P) is passed from ATP to another molecule, that molecule gains enegry; this is an endergonic (energy storage) reaction. Likewise, when that phosphate is removed, both energy and heat are given off (an exergonic reaction), and the molecule contains less energy than before.

See diagrams here:

• Glycolysis, Glycolysis
• ATP yield from glucose
• TCA cycle
• Mitochondrion, Mitochondrion
• ETC, ETC, ETC, ETC, ETC, ETC, ETC
• Oxidative phosphorylation
• Cori cycle, Cori cycle
  
• Gluconeogenesis, lactate and Cori cycle
• Glucose-alanine cycle, Glucose-alanine cycle
  
• beta-Oxidation
• Oxidation of palmitate (& everything else about lipids)
• Why minus 2 ATP for palmitate oxidation?
• Chemiosmotic theory
• Mitochondria, ETC and chemiosmotic theory
• Mitochondrial proton leak
• Inhibitors & uncouplers of ETC, Uncouplers of ETC
• Antimicrobials
• Lactic acidosis
• mDNA and nDNA mutations involving ETC complexes and oxidative phosphorylation, nuclear gene mutations, mitochondrial mutants
• Mitochondrial disease, Mitochondrial disease
• Cellular respiration
• Aerobic Energy System
• Cellular Respiration - Harvesting Chemical Energy (very good)
• Cell Biology - Endomembrane system, protein sorting and membrane trafficking (lots of diagrams)

Summary

1. Metabolism - all chemical reactions
2. Anabolic reactions - synthesis; catabolic reactions - breakdown
3. Phosphorylation - add P to a molecule to active/deactivate it; priming
4. Processing of energy-containing nutrients - 3 stages: 1) Digestion, 2) Anabolism/catabolism, and 3) Oxidative breakdown
5. Oxidation-Reduction (redox) reactions - 1) two reactions paired/always coupled, 2) electrons lost/gained, 3) involved coenzymes
6. Coenzymes - nicotinamide adenine dinucleotide (NAD+) and flavin adenine dinucleotide (FAD)
7. Mechanisms of ATP synthesis - 2 ways - 1) Substrate-level phosphorylation (SLP) - direct, and 2) Oxidative phosphorylation (OP) - Chemiosmotic processes - membrane & chemical reactions
8. Carbohydrate metabolism - complete oxidation of glucose - 3 stages - 1) Glycolysis, 2) Citric acid cycle/Krebs cycle/TCA cycle, and 3) ETC/OP
9. Complete oxidation of glucose: C6H12O6 + 6O2 --> 6H2O + 6CO2 + 36 ATP + heat
10. Glycolysis - breakdown of glucose to pyruvate - 3 phases - 1) Sugar activation - uses ATP to make fructose 1,6-biP, 2) Sugar cleavage - fructose 1,6-biP --> glyceraldehyde 3-P & dihydroxyacetone P, 3) Oxidation & ATP formation - 3C sugars oxidized (NAD+ reduced) and Pi attaches to each oxidized fragment. Final products of glycolysis: 6H2O + 6CO2 + 36 ATP + heat
11. Citric acid cycle/Krebs cycle/TCA cycle - fueled by pyruvic acid and free fatty acids (FFA)
12. Formation of acetyl CoA - 3-step process - 1) Decarboxylation, 2) Oxidation - removal of H atoms from pyruvic acid, and 3) Formation of acetyl CoA
13. Electron Transport Chain (ETC) - 1) Accepts H⁺, 2) Protein chain (cofactors), 3) Formation of oxygen, and 4) Release of energy - oxidative phosphorylation --> ATP
14. Mechanism of Oxidative Phosphorylation - 1) H --> H⁺ + e^-, 2) Proton pump --> proton motive force, 3) Electrons shuttled, 4) Formation of water, and 5) H⁺ diffuse --> ATP

PowerPoints

http://slideplayer.com/search/Energy+Metabolism/

http://slideplayer.com/slide/4352474/