NADH equivalents

The inner mitochondrial membrane is impermeable to NADH and NAD+, but NADH equivalents are moved from the cytosol to the matrix by either of two shuttles. NADH equivalents moved in by the malate-aspartate shuttle enter the respiratory chain at Complex I and yield a P/O ratio of 2.5 those moved in by the glycerol 3-phosphate shuttle enter at CoQ and give a P/O ratio of 1.5. 

In fact, the glyceraldehyde 3-phosphate dehydrogenase reaction also consumes NADH, equivalent to two molecules of NADH for each molecule of glucose synthesized. Since each cytosolic NADH would normally be used to generate approximately two ATP molecules via the glycerol 3-phosphate shuttle and oxidative phosphorylation (see Topic L2), this is equivalent to the input of another four ATPs per glucose synthesized. 

Asymmetric reduction of carbonyls has also been achieved by Dupas and coworkers by reaction of achiral NADH equivalents mediated by chiral aluminum Lewis acids [23]. They reduced methyl benzoyl formate with the dihydropyrido[2,3-h]indole 86 and chiral aluminum Lewis acids whose structures are drawn and 89 and 90 (Sch. 12). Asymmetric induction was quite low. Details of the reaction, including the conditions used, were not provided nor were the procedures used for the preparation of the chiral Lewis acids 89 and 90. 

The products of bioreactions can be reduced or oxidized, and all feasible pathways have to be redox neutral. There are several cofactors that transfer redox power in a pathway or between pathways, each equivalent to the reducing power of a molecule of H2, e.g., nicotinamide adenine dinucleotide (NADH), and these have to be included in the stoichiometric balances as H equivalents through redox balancing. For instance, for the reaction of glucose to glycerol (CHs/30), j NADH equivalent is consumed ... 

Other Reducing Agents. 1,4-Dihydropyridines such as 1-benzyl-1,4-di-hydronicotinamide (BNAH) are NADH equivalents capable of acting as good electron donors. These reagents have been used in the reductive desulfonyla-tion of a-nitro,90,91 a-keto,92 and a-cyanosulfones92 under sunlight irradiation. Based on the observed experimental results, these reactions seem to proceed via radical-anion species as shown in Scheme 2.91... 

The p-oxidation cycle (steps 2-5, Figure 23.7) consists of a set of four reactions whose overall form is similar to the last four reactions of the citric acid cycle. Each trip through the sequence of reactions releases acetyl CoA and returns a fatty acyl CoA molecule that has two fewer carbons. One molecule of FADH2, equivalent to two ATP molecules, and one molecule of NADH, equivalent to three ATP molecules, are produced for each cycle of p-oxidation. 

This number is either 3 or 5, depending on the mechanism used to shuttle NADH equivalents from the cytosol to the mitochondrial matrix see Figures 19-27 and 19-28. 

The soluble isozyme is generally considered to take part in the cytoplasmic side of the malate shuttle, providing a means of transporting NADH equivalents, in the form of malate, across the mitochondrial membrane. The mitochondrial enzyme, in addition to its role in the other half of the malate shuttle, is also a necessary component of the tricarboxylic acid cycle. The microbody malate dehydrogenase found in some plants appears to function in the glyoxylate cycle (5) or possibly in photorespiration ( ). 

This is the first of the reactions in which NADH is produced. One molecule of NADH is produced from NAD at this stage by the loss of two electrons in the oxidation. As we saw in our discussion of the pyruvate dehydrogenase complex, each NADH produced leads to the production of 2.5 ATP in later stages of aerobic metabolism. Recall also that there will be two NADH, equivalent to five ATP for each original molecule of glucose. 

Electron transfer pathways depend on reactions in both compartments. For example, NADH is produced in both the cytoplasm and the mitochondria. NADH equivalents from glycolysis must be transported into the mitochondria by the glycerol-phosphate shuttle or malate-aspartate shuttle. Furthermore, ATP that is produced in the mitochondria must be transported specifically to the cytoplasm to support the energy needs of many reactions. 

The hydroxylated fatty acyl CoA undergoes a second oxidation in which the hydroxyl group is oxidized to an oxo-group, yielding NADH (equivalent to 3 X ATP). 

Two or more linked enzyme reactions can lead to a change in the concentration of NADH or NADPH that is equivalent to the concentration of the original analyte. The reference glucose measurement using hexokinase [9001-51-8] and glucose-6-phosphate dehydrogenase [9001-40-5] is an example ... 

NADPH can be produced in the pentose phosphate pathway as well as by malic enzyme (Figure 25.1). Reducing equivalents (electrons) derived from glycolysis in the form of NADH can be transformed into NADPH by the combined action of malate dehydrogenase and malic enzyme ... 

The lower than expected yields can be explained by the nature of methane oxidation to methanol in these bacteria. This reaction, catalysed by methane mono-oxygenase, is a net consumer of reducing equivalents (NADH), which would otherwise be directed to ATP generation and biosynthesis. In simple terms the oxidation of methane to methanol consumes energy, lowering the yield. 

If the glycolytic flux is slow much of the pyruvate formed enters the mitochondria and is oxidized by the citrate cycle and reducing equivalents (2H) from NADH are oxidized indirectly (see below). When the flux is fast there is net production of... 

Reduced nicotinamide-adenine dinucleotide (NADH) plays a vital role in the reduction of oxygen in the respiratory chain [139]. The biological activity of NADH and oxidized nicotinamideadenine dinucleotide (NAD ) is based on the ability of the nicotinamide group to undergo reversible oxidation-reduction reactions, where a hydride equivalent transfers between a pyridine nucleus in the coenzymes and a substrate (Scheme 29a). The prototype of the reaction is formulated by a simple process where a hydride equivalent transfers from an allylic position to an unsaturated bond (Scheme 29b). No bonds form between the n bonds where electrons delocalize or where the frontier orbitals localize. The simplified formula can be compared with the ene reaction of propene (Scheme 29c), where a bond forms between the n bonds. 

There are other reactions apart from NADH reduction (Sect 4.1) where the hydride equivalent shifts between electron donors and acceptors without bond formation between the n bonds. The hydride equivalent transfer must be reactions in the transfer band. In fact, a photochemical reaction between donors and acceptors is similar to thermal reactions between strong donors and acceptors. This further supports the mechanistic spectrum (Scheme 32). 

The reduced NADH of the tespitatoty chain is in turn oxidized by a metalloflavoptotein enzyme—NADH dehydrogenase. This enzyme contains FeS and FMN, is tighdy bound to the tespitatoty chain, and passes te-ducing equivalents on to Q. 

As a result of oxidations catalyzed by the dehydrogenases of the citric acid cycle, three molecules of NADH and one of FADHj are produced for each molecule of acetyl-CoA catabohzed in one mrn of the cycle. These reducing equivalents are transferred to the respiratory chain (Figure 16-2), where reoxidation of each NADH results in formation of 3 ATP and reoxidation of FADHj in formation of 2 ATP. In addition, 1 ATP (or GTP) is formed by substrate-level phosphorylation catalyzed by succinate thiokinase. 

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