NADH dependent enzyme

The preference of many NADH-dependent enzymes for either re or si face of their respective substrates is known => some of these enzymes become exceptionally useful stereoselective reagents for synthesis. 

Rhin(bpy)3]3+ and its derivatives are able to reduce selectively NAD+ to 1,4-NADH in aqueous buffer.48-50 It is likely that a rhodium-hydride intermediate, e.g., [Rhni(bpy)2(H20)(H)]2+, acts as a hydride transfer agent in this catalytic process. This system has been coupled internally to the enzymatic reduction of carbonyl compounds using an alcohol dehydrogenase (HLADH) as an NADH-dependent enzyme (Scheme 4). The [Rhin(bpy)3]3+ derivative containing 2,2 -bipyridine-5-sulfonic acid as ligand gave the best results in terms of turnover number (46 turnovers for the metal catalyst, 101 for the cofactor), but was handicapped by slow reaction kinetics, with a maximum of five turnovers per day.50... 

NICOTINAMIDE COENZYMES (SREC-TRAL PROPERTIES) NADH-dependent enzymes, AQUACOBALAMIN REDUCTASES BENZENE 1,2-DIOXYGENASE DEHYDROASCORBATE REDUCTASE GLUTAMATE SYNTHASE GLYOXYLATE REDUCTASE 3-HYDROXYBENZOATE 6-MONOOXY-GENASE... 

MISCELLANEOUS REACTIONS OF DIHYDROPYRIDINES Additional tests for net hydride transfers initiated by single-electron transfer include the use of substrates in which such pathways would necessarily involve readily ring-opened cyclopropylmethyl or readily cyclized 5-hexenyl radicals. Products from these radical reactions are not formed in NAD+/ NADH dependent enzymic reductions or oxidations (Maclnnes et al., 1982, 1983 Laurie et al., 1986 Chung and Park, 1982). Such tests have also been applied in non-enzymic reductions. Thus cyclopropane rings in cyclopropyl 2-pyridyl ketones, or imines of formylcyclopropane (van Niel and Pandit, 1983, 1985 Meijer et al., 1984) survive Mg+2 catalysed reduction by BNAH or Hantzsch esters but are opened by treatment with tributylin hydride. 

Equation 21 depicts the reaction of the simplest NAD+/NADH-dependent enzyme, alcohol dehydrogenase153. This enzyme performs the last reaction in ethanol fermentation. Indicated in the equation is the fundamental finding on such reactions first reported by Westheimer, Vennesland and coworkers154-157. The hydrogen transfer is not only direct in both directions (as opposed to solvent-mediated), but is totally stereospecific in both directions for both the coenzyme and the substrate. The pro-R hydrogen is transferred from both the coenzyme and the substrate ethanol. This was an observation of enormous implications for NAD+-dependent reactions, in particular, and enzyme catalyzed reactions, in general, that has been borne out by literally hundreds of examples. 

The answer is e. (Murray, pp 190—198. Scriver, pp 1521—1552. Sack, pp 121-138. Wilson, pp 287-317.) The major fate of acetoacetyl CoA formed from condensation of acetyl CoA in the liver is the formation of 3-hydroxy-3-methylglutaryl CoA (HMG CoA). Under normal postabsorp-tive conditions, HMG CoA production occurs in the cytoplasm of hepatocytes as part of the overall process of cholesterol biosynthesis. However, in fasting or starving persons, as well as in patients with uncontrolled diabetes mellitus, HMG CoA production occurs in liver mitochondria as part of ketone body synthesis. In this process, HMG CoA is cleaved by HMG CoA lyase to yield acetoacetate and acetyl CoA. The NADH-dependent enzyme P-hydroxybutyrate dehydrogenase converts most of the acetoacetate to P-hydroxybutyrate, These two ketone bodies, acetoacetate and P-hydroxybutyrate, diffuse into the blood and are transported to peripheral tissues. 

One of the metabolites of LSD in the human body is 2-oxy-lsd. It is formed by liver microsomes by an NADH-dependent enzyme, ... 

Equation 21 depicts the reaction of the simplest NAD /NADH-dependent enzyme, alcohol dehydrogenase . This enzyme performs the last reaction in ethanol fermentation. Indicated in the equation is the fundamental finding on such reactions first reported by Westheimer, Vennesland and coworkers The hydrogen transfer is not only... 

Whilst the whole-cell approach has proved invaluable, the associated problems of overmetabolism and side reactions can be encountered. Another way to counter the problems of high cost in using isolated BVMOs is to use an NADH dependent enzyme, as NADH retails at approximately one tenth of the cost of NADPH. The Type 2 DKCMOs from Pseudomonas putida ATCC 17453 (= NCIMB 10007) are NADH dependent, and Grogan et al. were successftd in applying a complement of these enzymes, termed MOl, to the transformation of bicyclo[3.2.0]hept-2-en-6-one, to yield another enantiodivergent mix of lactones enantiomeric to those obtained... 

The reductive activation steps required by this antibiotic make it likely that, under prooxidant conditions, alternative toxicity mechanisms may be involved. After reductive activation, e.g., by NADPH- and NADH-dependent enzymes, MMC can be partly diverted from DNA alkylation in an oxidative environment by redox interaction with oxygen, leading to formation of reactive oxygen species (ROS). " ROS, then, may... 

The report that NADPH-HPR was located in the cytosol (11, 12) and the previous knowledge that hydroxypyruvate was able to leak out of the peroxisome (13, 14) enhanced speculation that NADPH-HPR could have the same function as peroxisomal NADH-HPR. It would appear that the evidence collected from LaPr 88/29, the first reported mutant plant of any species lacking NADH-HPR activity, that these speculations may be correct and that the alternative NADPH activity may form a useful backup to the NADH-dependent enzyme If in fact NADPH-HPR is present at higher concentrations in LaPr 88/29, it may explain some of the unusual characteristics associated with this mutant ... 

LaPr 88/29, provides a means for unrestricted study of the NADPH-dependent enzyme. From Table 1 it is possible to evaluate the contribution of the peroxisomal NADH-dependent enzyme to the total NADPH-dependent activity. It appeared that 81% of the total NADPH-dependent activity in wild-type barley, was due to the NADH-dependent enzyme, a figure that agrees with the earlier speculation of 75-85% (10), based on measurements of NADH and NADPH-dependent HPR in spinach. 

Kojima M, Toda F, Hattori K (1980) The cyclodextrin-nicotinamide compound as a dehydrogenase model simulating apoenzyme-coenzyme-substrate ternary complex system. Tetrahedron Lett 21 2721-2724 Kojima M, Toda F, Hattori K (1981) 3 Cyclodextrin-nicotinamide as a model for NADH dependent enzyme. J Chem Soc Perkin Trans 1 1647-1651... 

Taking all these results into consideration, the most plausible mechanism for VB A formation from 9 to 5 are illustrated in Figure 10. After the dehydration of the intramolecular aldol product [11], the double bond delocalized as 12 and the NADH-dependent enzyme delivered the hydride from the Si face at C4 or from the Re face at C3 (29). 

P(3HB) is one of the most commonly produced and most extensively studied SCL-PHA. Fig. 8.3 elucidates the enzymatic pathway for the biosynthesis of P(3HB). The biosynthetic pathway of P(3HB) synthesis involves three major reactions and three key enzymes. The first reaction is the condensation of two acetyl-CoA molecules (derived fiom the TCA cycle) to form acetoacetyl CoA. This reaction is catalysed by the enzyme fi-ketothiolase, which is encoded by the phaA gene. The second reaction is the reduction of acetoacyl CoA to (R)-3-hydroxybutyryl CoA. This reaction is catalysed by the NADH-dependent enzyme acetoacetyl-CoA... 

Also we have already reported syntheses of a- and 3-CD-nicotinamide as models for an NADH dependent enzyme. Tiie corresponding reduced forms were more stable in aqueous solution, and showed a large rate enhancement (15-50 times greater) in the reduction of ninhydrin, compared with monomeric NADH[4]. 

The preference of many NADH-dependent enzymes for either the re or si face of their respective substrates is known. This knowledge has allowed some of these enzymes to become exceptionally useful stereoselective reagents for synthesis. One of the most widely used is yeast alcohol dehydrogenase. Others that have become important are enzymes from thermophilic bacteria (bacteria that grow at elevated temperatures). Use of heat-stable enzymes (called extremozymes) allows reactions to be completed faster due to the rate-enhancing factor of elevated temp>erature (over 100 °C in some cases), although greater enantioselectivity is achieved at lower temperatures. 

A detailed mechanism of the transfer of hydride to a carbonyl group of a NADH dependent enzyme, R)-2-... 

Applications of lactate dehydrogenase L-Lactate dehydrogenases (LDH) prepared from mammalian and bacterial sources, are available commercially. They are known to produce (2S)-a-hydoxy acids with different hydrocarbon side-chains by reduction of a-keto acids in high enantiomeric purities and good chemical yields (Figure 12.10). As NADH-dependent enzymes, LDHs are used in combination with other enzymes, such as formate dehydrogenase (FDH), to regenerate the co-factor in situ. 

Hagler, L., Coppes, R. I., and Herman, R. H., 1976, Metmyoglobin reductase Identification of reduced nicotinamide adenine dinucleotide (NADH)-dependent enzyme activity from bovine heart which reduces metmyoglobin. Fed. Proc. 35 1423. 

The reduction of DANT by NADH-dependent enzymes similar to the pyridine-nuleotide-dependent reduction of 4-nitrobenzoate described by Angermaier and Simon (2) could be excluded for the Desulfovibrio isolate (39). Figure 10 summarizes the complete reduction of trinitrotoluene in pure cultures of strictly anaerobic bacteria, including the main processes and enzymes involved. 

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