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8885dc19690-7503/1/0411:32 AM Page692mac76mac76:385 Chapter 19 Oxidative Phosphorylation and Photophosphorylation acid B-oxidation pathway, and the pathways of amino in the cytosol, others are in mitochondria, and still oth acid oxidation--all the pathways of fuel oxidation ex- ers have mitochondrial and cytosolic isozymes cept glycolysis, which takes place in the cytosol. The NAD-linked dehydrogenases remove two hydrogen selectively permeable inner membrane segregates the atoms from their substrates. One of these is transferred intermediates and enzymes of cytosolic metabolic path- as a hydride ion ( H) to NAD; the other is released ways from those of metabolic processes occurring in the as H in the medium(see Fig. 13-15). NADH and matrix. However, specific transporters carry pyruvate, NADPH are water-soluble electron carriers that associ- fatty acids, and amino acids or their a-keto derivatives ate reversibly with dehydrogenases NADH carries elec into the matrix for access to the machinery of the citric trons from catabolic reactions to their point of entry int acid cycle. ADP and Pi are specifically transported into the respiratory chain, the nadh dehydrogenase com- the matrix as newly synthesized aTP is transported out. plex described below. NADPH generally supplies elec- trons to anabolic reactions. Cells maintain separate Electrons Are funneled to universal pools of NADPH and NADH, with different redox po Electron Acceptors tentials. This is accomplished by holding the ratios of [reduced formyoxidized form relatively high for Oxidative phosphorylation begins with the entry of elec- NADPH and relatively low for NADH. Neither NADHnor trons into the respiratory chain. Most of these electrons NADPH can cross the inner mitochondrial membrane arise from the action of dehydrogenases that collect but the electrons they carry can be shuttled across in- electrons from catabolic pathways and funnel them into directly, as we shall see universal electron acceptors--nicotinamide nucleotides Flavoproteins contain a very tightly, sometimes (NAD* or NADP)or flavin nucleotides (FMN or FAD). covalently, bound flavin nucleotide, either FMN or FAD Nicotinamide nucleotide-linked dehydroge-(see Fig 13-18). The oxidized flavin nucleotide can ac- nases catalyze reversible reactions of the following gen- cept either one electron (yielding the semiquinone eral types form) or two (yielding FADH, or FMNH2). Electron Reduced substrate nad= transfer occurs because the flavoprotein has a higher reduction potential than the compound oxidized. The oxidized substrate + nadh +H+ standard reduction potential of a flavin nucleotide, Reduced substrate NADP+= like that of NAD or NADP, depends on the protein with oxidized substrate NAdPH +H+ which it is associated. Local interactions with functional groups in the protein distort the electron orbitals in the Most dehydrogenases that act in catabolism are spe flavin ring, changing the relative stabilities of oxidized for NAD as electron acceptor (Table 19-1). Some and reduced forms The relevant standard reduction TABLE 19-1 Some Important Reactions Catalyzed by NAD(P)H-Linked Dehydrogen Reaction Location NAD-linked ar-Ketoglutarate CoA +NAD= succinyl-CoA+ CO2+ NADH+ H L-Malate NAd- oxaloacetate NAdh+ H M and C Pyruvate CoA NAd= acetyl-CoA CO 2 NADH +H Glyceraldehyde 3-phosphate Pi+ NAD 1, bisphosphoglycerate NADH+ H Lactate t NAD= pyruvate NADH+ H B-Hydroxyacyl-CoA + NAD+ B-ketoacyl-CoA NADH+ H NADP-linked Glucose 6-phosphate t NADP= 6-phosphogluconate NADPH H NAD- or NADP-linked Glutamate H20+ NAD(P)= a-ketoglutarate NHA NAD(P)H Isocitrate NAD(P)= a-ketoglutarate CO2+ NAD(P)H+ H M and C These reactions and their enzymes are discussed in Chapters 14 through 18.acid -oxidation pathway, and the pathways of amino acid oxidation—all the pathways of fuel oxidation except glycolysis, which takes place in the cytosol. The selectively permeable inner membrane segregates the intermediates and enzymes of cytosolic metabolic pathways from those of metabolic processes occurring in the matrix. However, specific transporters carry pyruvate, fatty acids, and amino acids or their -keto derivatives into the matrix for access to the machinery of the citric acid cycle. ADP and Pi are specifically transported into the matrix as newly synthesized ATP is transported out. 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 dehydrogenases catalyze reversible reactions of the following general types: Reduced substrate NAD oxidized substrate NADH H Reduced substrate NADP oxidized substrate NADPH H Most dehydrogenases that act in catabolism are specific for NAD as electron acceptor (Table 19–1). Some are yz yz 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 complex 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 indirectly, 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 accept 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, unlike 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 692 Chapter 19 Oxidative Phosphorylation and Photophosphorylation TABLE 19–1 Some Important Reactions Catalyzed by NAD(P)H-Linked Dehydrogenases Reaction* Location† NAD-linked -Ketoglutarate CoA NAD succinyl-CoA CO2 NADH H M L-Malate NAD oxaloacetate NADH H M and C Pyruvate CoA NAD acetyl-CoA CO2 NADH H M Glyceraldehyde 3-phosphate Pi NAD 1,3-bisphosphoglycerate NADH H C Lactate NAD pyruvate NADH H C -Hydroxyacyl-CoA NAD -ketoacyl-CoA NADH H M NADP-linked Glucose 6-phosphate NADP 6-phosphogluconate NADPH H C NAD- or NADP-linked L-Glutamate H2O NAD(P) -ketoglutarate NH4 NAD(P)H M Isocitrate NAD(P) -ketoglutarate CO2 NAD(P)H H yz M and C yz yz yz yz yz yz yz yz * These reactions and their enzymes are discussed in Chapters 14 through 18. † M designates mitochondria; C, cytosol. 8885d_c19_690-750 3/1/04 11:32 AM Page 692 mac76 mac76:385_reb: