OXIDATIVE PHOSPHORYLATION 19.1 Electron-Transfer Reactions in Mitochondria:- Electrons Are Funneled to Universal Electron Acceptors
Oxidative phosphorylation begins with the entry of electrons into the respiratory chain. Most of these electrons arise from the action of dehydrogenases that collect electrons from catabolic pathways and funnel them into universal electron acceptors—nicotinamide nucleotides (NAD+ or NADP+) or flavin nucleotides (FMN or FAD). Nicotinamide nucleotide–linked dehydroge nases catalyze reversible reactions of the following general types:
Reduced substrate + NAD+ ⇆ oxidized substrate +NADH+ H+
Reduced substrate + NAD+⇆ oxidized substrate+ NADPH+ H+
Most dehydrogenases that act in catabolism are specific for NAD+ as electron acceptor (Table 19–1). Some are in the cytosol, others are in mitochondria, and still others have mitochondrial and cytosolic isozymes. NAD-linked dehydrogenases remove two hydrogen atoms from their substrates. One of these is transferred as a hydride ion (: H+) to NAD+; the other is released as H in the medium (see Fig. 13–15). NADH and NADPH are water-soluble electron carriers that associate reversibly with dehydrogenases. NADH carries electrons from catabolic reactions to their point of entry into the respiratory chain, the NADH dehydrogenase com plex described below. NADPH generally supplies electrons to anabolic reactions. Cells maintain separate pools of NADPH and NADH, with different redox potentials. This is accomplished by holding the ratios of [reduced form]/[oxidized form] relatively high for NADPH and relatively low for NADH. Neither NADH nor NADPH can cross the inner mitochondrial membrane, but the electrons they carry can be shuttled across in directly, as we shall see.
Flavoproteins contain a very tightly, sometimes covalently, bound flavin nucleotide, either FMN or FAD (see Fig. 13–18). The oxidized flavin nucleotide can ac cept either one electron (yielding the semiquinone form) or two (yielding FADH2 or FMNH2). Electron transfer occurs because the flavoprotein has a higher reduction potential than the compound oxidized. The standard reduction potential of a flavin nucleotide, un like that of NAD or NADP, depends on the protein with which it is associated. Local interactions with functional groups in the protein distort the electron orbitals in the flavin ring, changing the relative stabilities of oxidized and reduced forms. The relevant standard reduction potential is therefore that of the particular flavoprotein, not that of isolated FAD or FMN. The flavin nucleotide should be considered part of the flavoprotein’s active site rather than a reactant or product in the electron transfer reaction. Because flavoproteins can participate in either one- or two-electron transfers, they can serve as intermediates between reactions in which two electrons are donated (as in dehydrogenations) and those in which only one electron is accepted (as in the reduction of a quinone to a hydroquinone, described below).
