Metabolic pathways involving Frd1p, Osm1p, Pdi1p and Ero1p. Under anaerobic conditions the TCA cycle operates as two branches, a reductive path (red color) and an oxidative path (turquoise color). Osm1p catalyses the last step of the reductive branch of the TCA-cycle where fumarate is converted to succinate and FAD is regenerated from FADH2. Frd1p catalyses the same reaction in the cytosol. The regenerated FAD is used inside the ER during the maturation of secretory proteins. The Pdi1p and Ero1p enzymes mediate the oxidative folding of proteins in the ER. When a nascent polypeptide is translocated into the ER the reduced cysteines are oxidised by Pdi1p giving rise to a disulphide bridge in the protein. The reduced Pdi1p is subsequently oxidised by the membrane bound Ero1p which transfers the electrons to oxygen via covalently bound FAD. In vitro experiments have shown that free FAD can act as the electron acceptor in the absence of oxygen.