NADPH-dependent enzyme

Shafiee, A., Motamedi, H. and King, A., Purification, characterization and immobilization of an NADPH-dependent enzyme involved in the chiral specific reduction of the keto ester M, an intermediate in the s3mthesis of an anti-asthma drug, montelukast, from Microbacterium campoquemadoensis (MB5614). App/. Microbiol. Biotechnol., 1998, 49, 709-717. 

SHIKIMATE DEHYDROGENASE SULFITE REDUCTASE VALINE DEHYDROGENASE ZEATIN aS-TRANS ISOMERASE NADPH DEHYDROGENASE NAD(P)H DEHYDROGENASE (QUINONE) NADPH-dependent enzymes, ACYL-ACYL-CARRIER-RROTEIN -DESA-TURASE... 

Based on analysis of enzyme preparations, the conversion of isoflavanones to pterocarpans was thought initially to be catalyzed by a single NADPH-dependent enzyme, termed the pterocarpan synthase (PTS). However, it was subsequently shown that in M. sativa the conversion of vestitone to medicarpin involves two enzymes, VR and 7,2 -dihydroxy-4 -methoxyisoflavanol (DMI) dehydratase (DMID). The reaction series from vestitone to the pterocarpan is thought to proceed by the VR-catalyzed reduction of vestitone to DMI, followed by the loss of water and formation of the C-O-C bridge between the heterocycle and the B-ring, catalyzed by DMID. 

Reactions catalyzed by 11 (3-hydroxysteroid and 17(3-hydroxysteroid dehydrogenases, (a) 11 (3-hydroxysteroid dehydrogenase type 1, an NADPH-dependent enzyme, catalyzes the conversion of the inactive steroid, cortisone, to cortisol, which is the biologically active glucocorticoid. 11 (3-hydroxysteroid dehydrogenase type 2, an NAD+-dependent enzyme, catalyzes the reverse direction, (b) 17(3-hydroxysteroid dehy-drogenase type 1, an NADPH-dependent enzyme, catalyzes the reduction of estrone to estradiol. Type 2, an NAD+-dependent enzyme, catalyzes the oxidation of estradiol to estrone. Type 3, an NADPH-dependent enzyme, catalyzes the reduction of androstene dione to testosterone. Type 4, an NAD+-dependent enzyme, catalyzes the oxidation of estradiol to estrone, and androstenediol to dehydroepiandrosterone. 

Sanguinarine 1 is the prototype of benzophenanthridine alkaloids which occur frequently in plants of the family Papaveraceae. It has anticancer activity and has become of commercial interest because of its antibacterial properties. It is known from biosynthetic studies that protopine 2 is a metabolite on the pathway to sanguinarine, and recent work has shown that a microsomal cytochrome P-450 NADPH dependent enzyme will hydroxylate protopine... 

The enzyme that catalyzes the stereospecific reduction of ketopantoic acid to D-pantoic acid was isolated in a crystalline form from Pseudomonas maltophilia [109] (see Tables 4 and 5). It is an NADPH-dependent enzyme and is strictly specific to ketopantoic acid. The observation that mutants lacking this enzyme require either D-pantoic acid or pantothenic acid for growth and that the revertants regain this activity indicates that the enzyme is ketopantoic acid reductase (EC 1.1.1.169) and is involved in the pantothenate biosynthesis. 

The rates of NADPH consumption in liver by the various NADPH-dependent enzymes indicate that GSH reductase has by far the highest rate to detoxify the reactive oxygen species generated by the various sources. 

The later steps of morphine biosynthesis have been investigated in P. somniferum cells and tissue. Notably, in morphine biosynthesis, (S)-reticuline is converted to (R)-reticuline, thereby epimerizing the stereocenter generated by norcoclaurine synthase at the start of the pathway (Fig. Id). (S)-reticuline is converted to (R)-reticuline through a 1,2-dehydroreticuline intermediate. Dehydroreticuline synthase catalyzes the oxidation of (S)-reticuline to 1,2-dehydroreticulinium ion (44). This enzyme has not been cloned but has been purified partially and shown to be membrane-associated. This intermediate then is reduced by dehydroreticuline reductase, an NADPH-dependent enzyme that stereoselectively transfers a hydride to dehydroreti-culinium ion to yield (R)-reticuline. This enzyme has not been cloned yet but has been purified to homogeneity (45). 

The enzyme steroid Sa-reductase is an NADPH-dependent enzyme that catalyzes the conversion of testosterone to dihydrotestosterone, a more potent androgen (Equation 17.54). 

Aflatoxins are metabolized by the NADPH-dependent enzyme system using cytochrome P450. In vitro liver metabolism studies have shown five different types of metabolic pathways for aflatoxin Bl reduction, hydroxylation, hydration, O-de-methylation, and epoxidation. All of these products contain hydroxide groups that allow them to be conjugated with glucuronic acid and sulfate, thus becoming detoxified. 

Following the formation of S-norcoclaurine, hydroxylation at C3 with subsequent methylation yields S-reticuline.24 Although the R form corresponds to the correct stereochemistry of morphine at C9, both R and S isomers of reticuline have been found to act as precursors for thebaine, codeine and morphine and it is therefore apparent that S-reticuline is con-verted to its R form.25 Inversion is best explained by formation of an intermediate 1,2-dehydroreticulinium ion 22, followed by stereospecific reduction to yield R-reticuline, Figure 3. An NADPH-dependent enzyme, 1,2-dehydroreticuline... 

Studies by Hodgson and Casida (1960, 1961) were the first investigations of CM oxidation by microsomal NADPH-dependent enzymes. There is evidence that oxidation is the more important route for some CM metabolism, not only in a pharmacokinetic but also in a toxicological perspective because, unlike hydrolysis that usually generates detoxication products, oxidative metabolites often retain the CM ester bond and can sometimes have more potent anti-ChE activity (Oonnithan and Ca.sida, 1968). 

The mutagenicity of the dinitropyrenes in the Salmonella/S9 assay was markedly reduced by NADPH-dependent enzyme activity. However, when the cytosol and microsome enzymes in the S9 preparation were separated, the activity increased in assays containing cytosol enzymes and decreased in the presence of... 

A key branch point in tropane alkaloid biosynthesis is the conversion of tropinone into either tropine or pseudotropine (or i/ -tropine), which possess opposite stereochemistry at the 3-hydroxyl position. Two different NADPH-dependent enzymes catalyze the stereospecilic reduction of tropinone the 3-carbonyl of tropinone is reduced to the 3a-hydroxy group of tropine by tropinone reductase I (TR-I) and to the 3jS-hydroxy group of pseudotropine by tropinone reductase II (TR-II). Genes encoding both TR-I and TR-II have been identified in the tropinone... 

Several studies have reported the production in microorganisms of plant enzymes that are involved in alkaloid biosynthesis [29, 99-102], In this sense, Unterlinner et al. [100] have cloned and expressed in Escherichia coli four cDNAs encoding for different isoforms of the Codeinone reductase NADPH-dependent enzyme isolated from Papaver somniferum. In this report has been investigated the substrate specificity of the enzyme and the structural analysis, being the first report about the cloning and expression of genes of the biosynthetic pathway of morphine [90],... 

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