NADPH structure

Figure 4. NADPH structure (A) and the hydride ion transfer pathway (B-D).

The structure of phthalate dioxygenase reductase that transfers electrons directly from NADPH to phthalate dioxygenase has been determined by X-ray crystallography (119). In class II or class III dioxygenases, the ferredoxin obligately transfers electrons from the reductase to the terminal dioxygenase (64a) it can be either a Rieske-type ferredoxin or a ferredoxin containing a 4-cysteine coordinated [2Fe-2S] cluster. 

Matthews DA, Alden RA, Bolin JT, Filman DJ, Freer ST, Hamlin R, Hoi WG, Kisliuk RL, Pastore EJ, Plante FT, Xuong N, Kraut J. Dihydrofolate reductase from Lactobacillus casei. X-ray structure of the enzyme methotrexate-NADPH complex. J Biol Chem 1978 253 6946-54. 

Zinc-containing alcohol dehydrogenases take up two electrons and a proton from alcohols in the form of a hydride. The hydride acceptor is usually NAD(P) (the oxidized form of nicotinamide adenine dinucleotide (NADH) or its phosphorylated derivative, NADPH). Several liver alcohol dehydrogenases have been structurally characterized, and Pig. 17.8 shows the environment around the catalytic Zn center and the bound NADH cofactor. 

Glutathione reductase (GR) catalyzes the reduction of oxidized glutathione (GSSG) to reduced glutathione (GSH) using NADPH provided from the hexose monophosphate pathway. GR, a ubiquitous flavoenzyme, maintains a high value of two for the GSH/GSSG ratio in the red blood cells. l,3-Bis(2-chloroethyl)-nitrosourea (BCNU) selectively inhibits cellular GR. GR is composed of two identical subunits, each of molecular mass 50 kDa (S8). The three-dimensional structure and mechanism of catalysis have been established for human GR (K17). 

Historically, leukocyte NADPH oxidase was the first discovered enzyme of this type the existence of this enzyme in neutrophils was reported in 1962-1966 [59-61]. (As the evidence of superoxide production in biological systems has been obtained several years later, at that time the nature of oxygen species produced by leukocytes was of course unknown.) And only about 10 years later, Babior et al. [62] have shown that the activation of human neutrophils resulted in the production of superoxide. The structure of leukocyte NADPH has been widely discussed and well-established [57]. Superoxide production catalyzed by NADPH oxidase is described by Reaction (5) ... 

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