Nicotinamide adenine dinucleotide mitochondrial oxidation

Insects poisoned with rotenone exhibit a steady decline ia oxygen consumption and the iasecticide has been shown to have a specific action ia interfering with the electron transport iavolved ia the oxidation of reduced nicotinamide adenine dinucleotide (NADH) to nicotinamide adenine dinucleotide (NAD) by cytochrome b. Poisoning, therefore, inhibits the mitochondrial oxidation of Krebs-cycle iatermediates which is catalysed by NAD. 

It is well known that the selective transport of ions through a mitochondrial inner membrane is attained when the oxygen supplied by the respiration oxidizes glycolysis products in mitochondria with the aid of such substances as flavin mononucleotide (FMN), fi-nicotinamide adenine dinucleotide (NADH), and quinone (Q) derivatives [1-3]. The energy that enables ion transport has been attributed to that supplied by electron transport through the membrane due to a redox reaction occurring at the aqueous-membrane interface accompanied by respiration [1-5],... 

The oxidation of reduced jS-nicotinamide adenine dinucleotide (NADH) by quinone derivatives (Q) by has been investigated extensively, since the reaction was considered to be essential in the proton transport and the energy accumulation occurring at the mitochondrial inner membrane [2]. However, most of fundamental work in this field has been done in homogeneous solutions [48-52] though the reaction in living bodies has been believed to proceed at the solution membrane interface. 

Figure 6.1 Pathways involved in glucose oxidation by plant cells (a) glycolysis, (b) Krebs cycle, (c) mitochondrial cytochrome chain. Under anoxic conditions. Reactions 1, 2 and 3 of glycolysis are catalysed by lactate dehydrogenase, pyruvate decarboxylase and alcohol dehydrogenase, respectively. ATP and ADP, adenosine tri- and diphosphate NAD and NADHa, oxidized and reduced forms of nicotinamide adenine dinucleotide PGA, phosphoglyceraldehyde PEP, phosphoenolpyruvate Acetyl-CoA, acetyl coenzyme A FP, flavoprotein cyt, cytochrome e, electron. (Modified from Fitter and Hay, 2002). Reprinted with permission from Elsevier...

ROS play a critical role in initiation of apoptosis through changes in mitochondrial permeability, andpoly(ADP-ribose) polymerase (PARP) activation. These processes provide additional mechanisms for oxidative damage in acute neural trauma and neurodegenerative diseases (Warner et al., 2004). PARP activation is accompanied by the depletion of nicotinamide adenine dinucleotide, NAD. Depletion of NAD leads to depletion of ATP, which in turn promotes neuronal cell death (Zhang etal., 1994 Ishikawaetal., 1999). 

Figure 1 The mitochondrial respiratory chain. Electron transfer (brown arrows) between the three major membrane-bound complexes (I, III, and IV) is mediated by ubiquinone (Q/QH2) and the peripheral protein c)dochrome c (c). Transfer of protons hnked to the redox chemistry is shown by blue arrows red arrows denote proton translocation. NAD+ nicotinamide adenine dinucleotide, FMN flavin mononucleotide, Fe/S iron-sulfur center bH,bi, and c are the heme centers in the cytochrome bc complex (Complex III). Note the bifurcation of the electron transfer path on oxidation of QH2 by the heme bL - Fe/S center. Complex IV is the subject of this review. N and P denote the negatively and positively charged sides of the membrane, respectively...

Oxidative phosphorylation The process by which adenosine triphosphate (ATP) is synthesized from a hydrogen ion gradient across the mitochondrial inner membrane. The hydrogen ion gradient is formed by the action of protein complexes in the mitochondrial membrane that sequentially transfer electrons from the rednced cofactors nicotinamide adenine dinucleotide (NADH) and FADH to molecnlar oxygen. Movement of hydrogen ions back into the mitochondrion via ATP synthase drives the synthesis of ATP. 

Glutamate dehydrogenase A mitochondrial enzyme present in all tissues that metabolizes amino acids. It catalyzes the oxidative deamination of glutamate to a-ketoglutarate using NAD+ as the electron acceptor to also produce nicotinamide adenine dinucleotide (NADH) and ammonia. The enzyme uses the reducing equivalents of nicotinamide adenine dinucleotide phosphate (NADPH) to perform the reverse reaction. 

Fenaminosulf reduces respiration in sensitive fungi. Thus, it inhibits the mitochondrial oxidation of nicotinamide adenine dinucleotide (NADH) in Pythium (Tolmsoff, 1962). On the other hand, in nonsensitive fungi (Rhizoctonia solani) a reductase has been identified which decomposes the active substance. But... 

The oxidation reactions involved are catalyzed by a series of nicotinamide adenine dinucleotide (NAD+) or flavin adenine dinucleotide (FAD) dependent dehydrogenases in the highly conserved metabolic pathways of glycolysis, fatty acid oxidation and the tricarboxylic acid cycle, the latter two of which are localized to the mitochondrion, as is the bulk of coupled ATP synthesis. Reoxidation of the reduced cofactors (NADH and FADH2) requires molecular oxygen and is carried out by protein complexes integral to the inner mitochondrial membrane, collectively known as the respiratory, electron transport, or cytochrome, chain. Ubiquinone (UQ), and the small soluble protein cytochrome c, act as carriers of electrons between the complexes (Fig. 13.1.1). 

Figure 3.8. Structures of vitamins or vitamin-derived molecules that function in oxidation-reduction reactions. The oxidation of these redox groups in the inner mitochondricil membrane contributes to the electron transport chain that carries electrons from the oxidation of glucose to oxygen and in the process pumps protons from one side to the other of the inner mitochondrial membrane (see Chapter 8 for details). The proton gradient thus formed is used to phosphorylate ADP to form 32 of the 36 ATPs resulting from the oxidation of one glucose molecule to six CO2 and six H2O molecules. A Vitamin B3, also called niacin or nicotinic acid, becomes converted to the amide (nicotinamide) and dressed up with a ribose sugar. Then, in a manner like that of riboflavin in B becomes phosphorylated to form nicotinamide mononucleotide (NMN) or further reacted with the addition of adenosine monophosphate (AMP) to form nicotinamide adenine dinucleotide (NAD). B Vitamin B2, also known as riboflavin, is shown converted to the forms involved in redox reactions such as those of the electron transport chain. (From Biochemistry, Second Edition, D. Voet and J. Voet, Copyright 1995, John Wiley Sons, New York. Reprinted with permission of John Wiley Sons, Inc.)...

Strolin-Benedetti et al., 2006). Most of these are zinc-containing cytosolic enzymes that use nicotinamide adenine dinucleotide/reduced nicotinamide adenine dinucleotide (NAD+/NADH) as the cofactor. In contrast, aldehyde dehydrogenases utilize NAD-I- and catalyze the irreversible oxidation of aldehydes to carboxylic acids (Testa and Kramer, 2007 Strolin-Benedetti et al., 2006 Marchitti et al., 2008). Some forms of aldehyde dehydrogenases are cytosolic and others are mitochondrial ... 

---