HSS2305-L6

Carbohydrate (Fatty Acid) Metabolism in the Mitochondria

• Mitochondria are the powerhouses of the cell, involved in vital processes including energy production (ATP), anabolism, calcium homeostasis, and apoptosis.
• TCA/Krebs/Citric Acid Cycle is a key step in cellular respiration, occurring in the mitochondrial matrix.
  • The cycle starts with the condensation of Acetyl-CoA (2 Carbons) with oxaloacetate (OAA; 4 C) to form citrate (6 C).
  • During the cycle, 2 carbons are lost as CO2, regenerating OAA.
  • The cycle produces 4 pairs of electrons carried by NADH and FADH2.
  • These electron carriers are then transported to the electron transport chain.
• Glycolysis is an anaerobic pathway that occurs in the cytosol, breaking down glucose into pyruvate.
  • It produces 2 ATP, 2 NADH, and 2 Pyruvate per glucose molecule.
  • Pyruvate can be further catabolized aerobically or anaerobically.
• PDH (Pyruvate Dehydrogenase) is a multienzyme complex that transforms and transports pyruvate into the mitochondrial matrix.
  • It decarboxylates pyruvate to form a 2-carbon acetyl group.
  • The acetyl group is transferred to Coenzyme A (HS-CoA) to produce Acetyl-CoA.
  • This process requires NAD+ and produces NADH.
  • The overall reaction is: Pyruvate + HS-CoA + NAD+ → Acetyl-CoA + CO2 + NADH + H+
• β (Fat)-Oxidation is a stepwise process that breaks down fatty acids in the mitochondrial matrix.
  • It produces Acetyl-CoA, which can then enter the TCA cycle.
  • It also generates reducing equivalents (NADH and FADH2).

Oxidative Phosphorylation

• Electron Transport Chain is located in the inner mitochondrial membrane, utilizing electrons from NADH and FADH2.
  • These electrons pass through a chain of protein complexes (I-IV).
  • Complex I (NADH dehydrogenase) and Complex II (Succinate Dehydrogenase) receive electrons from NADH and FADH2, respectively.
  • Electron transport through the chain pumps H+ ions from the mitochondrial matrix to the intermembrane space.
  • This generates a proton gradient and mitochondrial membrane potential.
  • Oxygen is consumed at Complex IV (Cytochrome oxidase) as the final electron acceptor.
• ATP Synthase (Complex V) uses the potential energy from the proton gradient to produce ATP through chemiosmosis.
  • Each NADH yields approximately 2-3 ATP molecules.
  • Each FADH2 yields approximately 2 ATP molecules.
  • The theoretical yield of ATP per glucose molecule is 36.
  • However, actual yield is typically lower, between 28-32 ATP per glucose.

ATP

• Adenosine Triphosphate (ATP) is the universal energy currency of the cell.
  • It stores chemical energy that can be released through hydrolysis, forming ADP (adenosine diphosphate) and inorganic phosphate.
  • This reaction releases approximately 7.3 kcal/mole of free energy.
  • ATP powers essential cellular processes:
    • Active transport of molecules and ions
    • Nerve impulses
    • Maintenance of cell volume
    • Protein phosphorylation
    • Muscle contraction
    • Cilia and flagella beating
    • Bioluminescence

ATP: Other Functions

• Cell Signalling: ATP serves as a substrate in signal transduction pathways by kinases, which phosphorylate proteins and lipids. ATP is also utilized by adenylyl cyclase to produce cyclic AMP, a second messenger molecule.
• Anabolism: ATP is a monomer used in the synthesis of RNA and DNA (after conversion to deoxyATP).

Cataplerosis

• Cataplerosis refers to the use of metabolic intermediates from the TCA cycle for anabolic processes.
  • These intermediates are utilized in the synthesis of various anabolic molecules.
  • Example: Oxaloacetate can be used for gluconeogenesis.
• Mitochondrial Matrix contains circular DNA (mtDNA), ribosomes, and enzymes essential for the TCA cycle and other metabolic processes.

Mitochondrial Structure

• Mitochondrial Membranes are highly proteinaceous, containing approximately 50% protein in the outer membrane and 75% in the inner membrane.
• Outer Membrane:
  • Highly permeable due to the presence of Porin, a large pore-forming protein.
  • Allows the exchange of ions, small molecules, NADH, and ATP.
• Inner Membrane:
  • Contains the electron transport chain and cristae, which are invaginations or folds that increase the surface area.
  • Largely impermeable to most molecules, except for:
    • O2
    • CO2
    • H2O
  • Contains specialized transport systems (uniports and antiports) for specific metabolites.
  • The regulated permeability is key for the bioenergetics of the cell.
• Matrix:
  • The innermost compartment of the mitochondria.
  • Contains:
    • mtDNA
    • Ribosomes
    • Enzymes for the TCA cycle, β-oxidation, and other metabolic pathways.
  • Can synthesize RNA and proteins.

Mitochondrial DNA (mtDNA)

• Encodes for 13 proteins, all part of the electron transport chain.
• Multiple copies of mtDNA exist within each cell, typically more than nuclear genes.
• Inherited primarily from mothers through the oocyte mitochondria.
• Used to track human migration and evolution because it mutates at a faster rate than nuclear DNA.
• Single nucleotide polymorphisms can be used to study maternal ancestry.
• However, most mitochondrial proteins are encoded by nuclear DNA, not mtDNA.

Mitochondrial Dynamics

• Mitochondrial Biogenesis: the creation of new mitochondria.
• Mitophagy: the selective degradation of old or dysfunctional mitochondria via autophagy.
  • Autophagy involves lysosomal recycling of cellular components.
• Fusion: mitochondria can fuse with one another, creating larger and interconnected networks.
• Fission: mitochondria can divide into two daughter mitochondria.
  • The endoplasmic reticulum (ER) might play a role in inducing fission.
  • Fusion and fission are crucial for maintaining the number, length, and interconnection of mitochondria.

Explore the intricate processes of carbohydrate metabolism, particularly the roles of mitochondria in energy production through the TCA cycle and glycolysis. This quiz covers major concepts like the transformation of Acetyl-CoA and the importance of NADH and FADH2 in cellular respiration.