NADPH-dependent

An en2ymatic method for assessing riboflavin deficiency in humans has been developed (74). It is based on the fact that NADPH-dependent glutathione reductase of red cells reflects riboflavin fluctuations. 

FIGURE 25.32 A reaction mechanism for HMGCoA reductase. Two successive NADPH-dependent reductions convert the thioester, HMGCoA, to a primary alcohol. 

Glucuronate is reduced to L-gulonate in an NADPH-dependent reaction L-gulonate is the direct precursor of ascorbate in those animals capable of synthesizing this vitamin. In humans and other primates as well as guinea pigs, ascorbic acid cannot be synthesized because of the absence of L-g ulonolactone oxidase. L-Gulonate is metabolized ultimately to D-xylulose 5-phosphate, a constituent of the pentose phosphate pathway. 

Trinitrophenol is degraded in a reaction involving ring reduction by hydride transfer from an NADPH-dependent F420 reductase (Hofmann et al. 2004). 

Kaufmann F, DR Lovley (2001) Isolation and characterization of a soluble NADPH-dependent Fe(lll) reductase from Geobacter sulfurreducens. J Bacteriol 183 4468-4476. 

An enzyme that catalyzes the reduction of A -piperidein-2-carboxylate to piperidine-2-car-boxylate (r-pipecolate) in the catabolism of o-lysine by Pseudomonas putida ATCC12633 is an NADPH-dependent representative of a large family of reductases that are distributed among bacteria and archaea (Muramatsu et al. 2005). It also catalyzes the reduction of A -pyrrolidine-2-carboxylate to L-proline. 

Chen H, SL Hopper, CE Cemiglia (2005) Biochemical and molecular characterization of an azoreductase from Staphylococcus aureus, a tetrameric NADPH-dependent flavoprotein. AficrofcioZogy ff/W) 151 1433-1441. 

Muramatsu H, H Mihara, R Kakutani, M Yasuda, M Ueda, T Kurihara, N Esaki (2005) The putative malate/ lactate dehydrogenase from Pseudomonas putida is an NADPH-dependent ALpiperideine-2-carboxyl-ate/A -pyrroline-2-carboxylate reductase involved in the catabolism of L-lysine and D-proline. J Biol Chem 280 5329-5335. 

Swaving J, JAM de Bont, A Westphal, A de Kok (1996) A novel type of pyridine nucleotide-disulfide oxidore-ductase is essential for NAD - and NADPH-dependent degradation of epoxyalkanes by Xanthobacter strain Py2. J Bacteriol 178 6644-6646. 

Romanov V, RP Hausinger (1996) NADPH-dependent reductive ortho dehalogenation of 2,4-dichlorobenzoic acid in Corynebacterium sepedonicum KZ-4 and coryneform bacterium strain NTB-1 via 2,4-dichlo-robenzoyl coenzyme A. J Bacteriol 178 2656-2661. 

Fontecave, M., Mansuy, D., Jaouen, M. and Pezerat, H. (1987). The stimulator) effects of asbestos on NADPH-dependent lipid peroxidation in rat liver microsomes. Biochem. J. 241, 561-565. 

Oxatomide (l- 3- [4-(diphenylmethyl)-l-piperazinyl] propyl)-l,3-dihydro-2H-benzimidazol-2-one) is an antiallergy drug. Akamatsu has reported that oxatomide decreases neutrophil-generated superoxide anion and hydrogen peroxide formation in a dose-dependent manner. The authors hypothesize that the drug is inhibiting NADPH-dependent oxygen metabolism within the neutrophil (Akamatsu et al., 1993). 

Kataoka, M., Hoshino-Hasegawa, A., Thiwthong, R. et al. (2006) Gene cloning of an NADPH-dependent menadione reductase from Candidamacedoniensis, and its application to chiral alcohol production. Enzyme and Microbial Technology, 38 (7), 944—951. 

Wada, M., Kataoka, M., Kawabata, H. et al. (1998) Purification and characterization of NADPH-dependent carbonyl reductase, involved in stereoselective reduction of ethyl 4-chloro-3-oxobutanoate, from Candida magnoliae. Bioscience Biotechnology and Biochemistry, 62 (2), 280-285. 

Zhu, D. and Hua, L. (2006) Enantioselective enzymatic reductions of sterically bulky aryl alkyl ketones catalyzed by a NADPH-dependent carbonyl reductase. The Journal of Organic Chemistry, 71 (25), 9484—9486. 

Cundari, T.R., Dinescu, A., Zhu, D. andHua, L. (2007) A molecular modeling study on the enantioselectivity of aryl alkyl ketone reductions by a NADPH-dependent carbonyl reductase. Journal of Molecular Modeling, 13 (6-7), 685-690. 

Enoate reductase reduces a,/3-unsaturated carboxylate ions in an NADPH-dependent reaction to saturated carboxylated anions. Useful chiral synthons can be conveniently prepared by the asymmetric reduction of a triply substituted C—C bond by the action of enoate reductase, when the double bond is activated with strongly polarizing groups [22]. Enoate reductases are not commercially available as isolated enzymes therefore, microorganisms such as baker s yeast or Clostridium sp. containing enoate reductase are used to carry out the reduction reaction. 

DHFR has been the object of intense research for the last few decades. The enzyme catalyses the NADPH-dependent reduction of 7,8-dihydrofolate to 5,6,7,8 tetrahydrofolate, a chemical which participates in the thymidilate synthesis cycle. Thus, the enzyme is crucial in the synthesis of thymidine monophosphate as well as in various one-carbon unit transfer reactions. 

Fig. 1. The metabolic cycle for the synthesis and degradation of poly(3HB). (1) 3-ketothiolase (2) NADPH-dependent acetoacetyl-CoA reductase (3) poly(3HB) synthase (4) NADH-dependent acetoacetyl-CoA reductase (5), (6) enolases (7) depolymerase (8) d-(-)-3-hydroxybutyrate dehydrogenase (9) acetoacetyl-CoA synthetase (10) succinyl-CoA transferase (11) citrate synthase (12) see Sect. 3...

The kind of enantiomer [d-(-)- or l-(+)-] synthesized in the formation of the C4 intermediate varies. The acetoacetyl-CoA reductase (EC 1.1.1.36), which is NADPH-dependent, stereoselectively reduces acetoacetyl-CoA to d-(-)-3-hydroxybutyryl-CoA (R. eutropha [15]). The NADH-dependent reductase catalyzes the reduction of acetoacetyl-CoA to L-(+)-3-hydroxybutyryl-CoA. Afterwards two stereospecific crotonyl-CoA hydratases, l-(+)- and D-(-)-speci-fic, convert the L-(+)-3-hydroxybutyryl-CoA into the D-(-)-isomer (Rhodo-spirillum rubrum [16]). 

The NADPH-dependent reductase is active with C4 to C6 D-(-)-3-hy-droxyacyl-CoAs, it has no activity with L-(+)-substrates, and the reduction of acetoacetyl-CoA yields only D-(-)-3-hydroxybutyryl-CoA. The NADH-de-pendent reductase can use the L-(+)-enantiomers of these compounds and, in addition, C7, C8, and C10 L-(+)-3-hydroxyacyl-CoAs as substrates. From aceto-acetyl-CoA the NADH-dependent reductase produces only L-(+)-3-hydro-xybutyryl-CoA, but in the reverse direction it is active with both substrates [15]. 

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