Table 1.
Enzyme | Substrate | Group | Source/Topology | Comments |
---|---|---|---|---|
Alpha keto glutarate dehydrogenase | Alpha keto glutarate. | NAD+/NADH | FAD of E3 dihydrolipoamide dehydrogenase. Matrix. | ROS production is inhibited by high ATP and aspartate [69] and regulated by reversible thiol oxidation [105]. Favored by high NAD+/NADH ratio. May also produce H2O2. Requires substrate. Ca2+ sensitive. |
Pyruvate dehydrogenase | Pyruvate. | NAD+/NADH | FAD of E3 dihydrolipoamide dehydrogenase. Matrix. | Regulated by reversible thiol oxidation [105] and phosphorylation. ROS production is favored by high NAD+/ NADH ratio. May also produce H2O2. Requires substrate. |
Branched-chain 2-oxoacid dehydrogenase complex | Branched chain 2-oxoacids (e.g., 3-methyl-2-oxopentanoate). | NAD+/NADH | FAD of E3 dihydrolipoamide dehydrogenase. Matrix | Favored by high NAD+/NADH ratio. Requires substrate. |
Aminoadipate dehydrogenase complex | 2-oxoadipate. | NAD+/NADH | FAD of E3 dihydrolipoamide dehydrogenase. Matrix | ROS production is favored by high NADH/NAD+ ratio. Requires substrate. |
sn-glycerol-3-phosphate dehydrogenase | Glycerol 3-phosphate | UQ/UQH2 | UQ binding site but may also involve a flavin. Intermembrane space and matrix. | Ca2+ sensitive—can enhance ROS production at low substrate levels [106]. Requires substrate. Much emanates from complex II. |
Dihydroorotate dehydrogenase | Dihydroorotate | UQ/UQH2 | UQ binding site. Matrix. | Relatively low superoxide producing capacity but can drive other sites to high rates by reducing the Q pool [107]. |
Electron transferring-flavoprotein: ubiquinone oxidoreductase | Electron transferring flavoprotein (involved in lipid + amino acid metabolism). | UQ/UQH2 | May emanate from the flavin but origin is unclear [69]. | ROS production is quite low even when other sites are inhibited [108], suggesting main contribution under native conditions is to reduce the Q pool. |