Pyruvate dehydrogenase
Localization of Krebs Cycle: The Krebs Cycle occurs in the matrix of mitochondria, while glycolysis takes place in the cytosol of cells. Pyruvate enters the mitochondrion to be metabolized further.
Mitochondrial compartments
The mitochondrion is comprised of several compartments:
- Outer membrane: Contains large channels and is leaky to ions and small molecules.
- Intermembrane space: The space between the inner and outer membranes.
- Inner membrane: Contains infoldings called cristae, which house components of the respiratory chain and ATP Synthase. It acts as the major permeability barrier and contains transport catalysts, including a carrier protein for pyruvate entry into the matrix.
- Matrix: Contains the Pyruvate Dehydrogenase complex, Krebs Cycle, and enzymes for fatty acid oxidation and amino acid metabolism.
Pyruvate dehydrogenase complex
The Pyruvate Dehydrogenase catalyzes the oxidative decarboxylation of pyruvate to form acetyl-CoA, with a free energy change (G) of -33.4 kJ/mol. It is a large complex consisting of multiple copies of three enzymes: E1, E2, and E3.
- Core of the complex: Consists of 60 copies of E2.
- Periphery of the complex: Includes 30 copies of E1 (a tetramer with α and β subunits), 12 copies of E3 (a homodimer), and 12 copies of an E3 binding protein linking E3 to E2.
Pyruvate dehydrogenase subunits
| Enzyme | Abbreviated | Prosthetic Group |
|---|---|---|
| Pyruvate Dehydrogenase | E1 | Thiamine pyrophosphate (TPP) |
| Dihydrolipoyl Transacetylase | E2 | Lipoamide |
| Dihydrolipoyl Dehydrogenase | E3 | FAD |
The Pyruvate Dehydrogenase Complex requires five different coenzymes: TPP, FAD, CoA, NAD, and lipoate. Four of these coenzymes are derived from vitamins: Thiamin (TPP), riboflavin (FAD), pantothenate (CoA), and niacin (NAD).
The E. coli Pyruvate Dehydrogenase Complex has a molecular weight of approximately 4600 kDa and a diameter of about 300 Å.
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