Pyruvate Dehydrogenase

Glycolysis occurs in the cytosol of cells.
Pyruvate enters the mitochondrion to be metabolized further.
Mitochondrial Compartments:
The matrix contains Pyruvate Dehydrogenase, enzymes of Krebs Cycle, and other pathways, e.g., fatty acid oxidation & amino acid metabolism.
The outer membrane contains large VDAC channels, similar to bacterial porin channels, making the outer membrane leaky to ions & small molecules.
The inner membrane is the major permeability barrier of the mitochondrion.
It contains various transport catalysts, including a carrier protein that allows pyruvate to enter the matrix.
It is highly convoluted, with infoldings called cristae.
Embedded in the inner membrane are constituents of the respiratory chain and ATP Synthase.
Pyruvate Dehydrogenase, catalyzes oxidative decarboxylation of pyruvate, to form acetyl-Co
Pyruvate Dehydrogenase: a large complex containing many copies of each of 3 enzymes, E1, E2, & E3.
The inner core of mammalian Pyruvate Dehydrogenase is an icosahedral structure consisting of 60 copies of E2.
At the periphery of the complex are:
30 copies of E1 (itself a tetramer with subunits a2b2).
12 copies of E3 (a homodimer), plus 12 copies of an E3 binding protein that links E3 to E2.
FAD (Flavin Adenine Dinucleotide is derived from the vitamin riboflavin. The dimethylisoalloxazine ring system undergoes oxidation/reduction.
FAD is a prosthetic group, permanently part of E3.
Reaction: FAD + 2 e- + 2 H+