Scheme 1.
: Oxidation of cytosolic NAD(P)H by DWM and PCM and kinetic parameters of the enzymes involved. Cytosolic NADH is oxidized by the MAL/OAA shuttle: MAL enters mitochondria, then it is converted via mitochondrial MDH (mMDH) in OAA, which is released in the extramitochondrial phase in exchange with entering MAL; once in the extramitochondrial phase, OAA is converted in MAL via cytosolic MDH (cMDH) with NADH consumption. On the basis of the kinetic parameters summarized in Scheme (see later for explanation), at physiological concentration of NADH (less than 1 μm), the oxidation by the NADH DHExt is expected to be negligible (see also Fig. 6). NADPH oxidation occurs as due to NADPH DHExt, whereas cMDH shows no specificity toward NADPH. i.m.m., inner mitochondrial membrane; i.s., intermembrane space; o.m.m., outer mitochondrial membrane.