On the need for regulation of succinate dehydrogenase

It has been known since 1955 that substrates and competitive inhibitors of succinate dehydrogenase activate the enzyme by a process which is believed to involve a conformation change in the enzyme [ 1, 21. The activation is completely reversible, since on removal of the substrate the activated enzyme rapidly reverts to the unactivated (inactive) form [3]. This type of activation has been observed in soluble and particulate preparations, in inner mem- brane preparations and in mitochondria [2-41. More recently a second type of reversible activation of the enzyme was discovered [5, 61. It was noted that in inner membrane preparations (ETP or ETPB) NADH also activates the enzyme reversibly. Studies with suitable inhibitors indicated that NADH itself is not the direct activator, but merely serves to reduce endo- genous ubiquinone, so that the reduced quinone ap- pears to be the immediate activating agent. This con- clusion was verified by two experimental approaches: (1) reduced ubiquinone (CoQ,,H,) is at least as good an activator as NADH in membrane preparations and (2) in pentane-extracted preparations, which are de- void of CoQie, NADH no longer activates, but succi- nate or malonate still do; on reincorporation of the CoQie activation by NADH is restored [S, 61, Acti- vation via CoQ,,H2 is characterized by the same ki- netic and thermodynamic parameters as by substrates, and thus might involve the same type of conformation- al alteration. Since the reduced/oxidized CoQic ratio undergoes