NADH cytochrome b reductase

NADH-CYTOCHROME b REDUCTASE EERROCHELATASE EERROMAGNETIC Eerromagnetic substances,... 

Cytochrome fcs/NADH cytochrome b reductase (human) Reductive detoxification of substituted hydroxylamine carcinogens (K = 200-400 p.M) 27-29, 50... 

Hereditary methemoglobinemia arises from a deficiency of the enzyme that catalyzes this reduction, NADH-cytochrome b reductase. 

This reaction is catalyzed by a complex of three membrane-bound proteins NADH-cytochrome bs reductase, cytochrome b, and a desaturase (Figure 22.32). First, electrons are transferred from NADH to the FAD moiety of NADH-cytochrome b reductase. The heme iron atom of cytochrome h-, is then reduced to the Fe state. The nonheme iron atom of the desaturase is subsequently converted into the Fe state, which enables it to interact with and the saturated fatty acyl CoA substrate. A double bond is... 

CYP oxidation reactions involve a complex series of steps that have been well defined Rose and Hodgson, 2004). The initial step involves the binding of substrate to oxidized CYP, followed by a one-electron reduction catalyzed hy NADPH cytochrome P450 reductase to form a reduced cytochrome-substrate complex. The next several steps involve interaction with molecular oxygen, the acceptance of a second electron from NADPH cytochrome P450 reductase or NADH cytochrome b reductase, followed by the subsequent release of water and the oxygenated product of the reaction. This complicated reaction sequence results in the transfer of one atom of molecular oxygen to the substrate while the other atom is reduced to water. 

The A -desaturase system consists of three major proteins (1) NADH-cytochrome b reductase, (2) cytochrome bj, and (3) a terminal desaturase component (Fig. 3.3). Under most circumstances, electron transport greatly exceeds the activity of the rate-limiting desaturase component. The A -desaturase contains one atom of a nonheme. 

Owing to the wide range of reactions in which flavin coenzymes are involved, a unitary mechanism of action appears unlikely. It seems clear that in enzymes where the fully reduced form is reacting with a one-electron acceptor (such as NADH-cytochrome b-reductase, NADPH-cytochrome c-reductase, and ferridoxin NADP reductase), the mechanism involves flavin semiquinones as intermediates. These are free-radical intermediates and can be detected by electron spin resonance (ESR). Flavin semiquinones can be stabilized because of multiple resonance forms, the odd electron being shared throughout the entire isoalloxazine ring. The free-radical intermediate may be further oxidized or reduced, one electron at a time. A number of enzjmies requir-... 

Benzoate 1,2-dioxygenase was shown to catalyze the conversion of benzoate to l,2-dihydro-l,2-dihydroxybenzoic acid (DHB) in the presence of NADH and oxygen by Reiner et al.205, 206). Yamaguchi et al.61> have demonstrated that the enzyme system consists of two components (A and B),both of which are required for benzoate 1,2-dioxygenase activity. Component A shows NADH-cytochrome c reductase activity and component B appears to be dioxygenase, thus the following reaction scheme is suggested [Eq. (25)]. 

Hackett, C.S., Novoa, W.B., Ozols, J. Strittmatter, P. (1986). Identification of the essential cysteine residue of NADH-cytochrome b5 reductase. Journal of Biological Chemistry 261, 9854-7. 

The mechanism for NADH-cytochrome bs reductase described in Section VII,B was worked out with the soluble enzyme, and the question of its applicability to the interaction of the amphipathic proteins can now be considered. 

This reaction is catalyzed by a complex of three membrane-bound enzymes NADH-cytochrome h reductase, cytochrome b, and a desaturase (Figure 22.29). First, electrons are transferred from NADH to the FAD moiety of NADH-cytochrome b 5 reductase. 

Figure 13.2. Catalytic cycle of cytochrome P450 associated with monooxygenase reactions. (Fe " ), ferricytochrome P450 hs, high spin Is, low spin (Fe " ), ferrocytochrome P450 Fpi, flavoprotein 1-NAJDPH-cytochrome P450 reductase Fpg, NADH-cytochrome bg reductase cyt b cytochrome b, XH, substrate (modified from Ref 6).

Fig. 6. Biosynthesis of ethanolamine plasmalogens by I -alkyl desaturase. Components of the enzyme complex responsible for this unusual desaturation between carbons 1 and 2 of the 0-alkyl chain are (I) NADH cytochrome h, reductase, (II) cytochrome b, and (III) Al -alkyl desaturase, which is cyanide-sensitive. GPE, jn-glycero-3-phosphoethanolamine.

A number of other cytochromes are located in the intermembrane space and the inner surface of the outer mitochondrial membrane. Cyt bs (cytochrome bs) is a small heme protein with a hydrophilic domain of about 95 amino acids and a carboxyl terminus of about 45 hydrophobic amino acids that serve to anchor the protein to the inner surface of the outer mitochondrial membrane.Cyt bs is reduced by NADH-cyt b reductase, also located on the inner surface of the outer membrane. Under conditions of high intermembrane ionic strength, Cc is released from the inner membrane, and can transport electrons from cyt bs on the outer membrane to CcO on the inner membrane. Cyt bs contains protoheme b with the iron atom ligated by two histidine nitrogen atoms. The heme group has a reduction potential of +10 mV versus NHE. Cyt bs is also found on the liver endoplasmic reticulum membrane, where it transfers electrons from NADH-cyt b5... 

Tryptophan synthase, Tryptophan-tRNA synthetase, Methionyl-tRNA synthetase, Tryptophanase 200- 230 NADH-cytochrome b5 reductase, Thloredoxin 220- 250 Prothrombin, Cytochrome b5, Hygromycin B phosphotransferase 2A0- 270 DNA Invertase, Cytochrome oxidase, RNA polymerase s. 

Lamb DC, Kelly DE, Maiming NJ, Kaderbhai MA, Kelly SL (1999) Biodiversity of the P450 catalytic cycle yeast cytochrome b(5)/NADH cytochrome b(5) reductase complex efflciently drives the entire sterol 14-demethylation (CYP51) reaction. FEBS Lett 462 283-288... 

When air is admitted to an anaerobic yeast culture, respiration reaches normal values within about 4 hours [21]. The cytochrome bands at 556 mfi and 580 m/i are replaced by the bands of cytochromes c, b, and a [19]. Additionally, succinate-cytochrome c reductase activity rises. Catalase and cytochrome peroxidase activities increase over 30-fold, as do NADH-cytochrome c reductase, lactate-cytochrome c reductase, and a-glycerophosphate-cytochrome c reductase. Enzymes of the tricarboxylic acid cycle also increase in activity [21]. 

Isoectane extracts only a small fraction of the vitamin E associated with the NADH cytochrome c reductase system. Added lipids could restore the activity of the system because they fulfill nonspecific functions proper to many lipids, including vitamin E. Therefore, added lipids could spare the vitamin E remaining in the isoectane-extracted system for participation in the electron transport chain. This possibility is in keeping with observations made in Mason s laboratory, in which the vitamin E content of the NADH cytochrome c reductase system was completely extracted in that case the activity of the system is restored by a-tocopherol, and apparently by a-tocopherol only. Unfortunately, activity is not restored in all the preparations tested, probably because many uncontrollable factors can influence the preparations. In these experiments, antimycin A acts as a competitive inhibitor of a-tocopherol. Therefore, it appears that vitamin E is in some way involved in electron transport between cytochrome b and cytochrome c. Furthermore, among a number of lipids tested, only tocopherol can prevent antimycin A inhibition of NADH cytochrome c reductase. 

There are three proteins required for the formation of unsaturated fatty acids from precursor saturated acids by the microsomal electron-transport chain. They are NADH-cytochrome reductase, cytochrome 5, and acyl-CoA desaturase. The reaction sequence (Fig. lA) requires molecular oxygen as a proton acceptor, and electrons from NADH. The electron-transport sequence commences with the reductase, passes through cytochrome b, and terminates with the cyanide-sensitive factor, acyl-CoA desaturase (Enoch et al., 1976). Both cytochrome b reductase and cytochrome b are amphipathic proteins in which the redox center is located at the hydrophilic end while the hydrophobic portion binds to lipid moieties (DePierre and Ernster, 1977). Several studies have demonstrated the ability of cytochrome b and cytochrome b reductase to undergo lateral diffusion both in microsomes and in liposomes during the course of electron transfer (Hackenbrock, 1976). 

NADH-cytochrome reductase NADH NAD + FAD Fe respira-tory chain cytochrome b ... 

This impressive reaction is catalyzed by stearoyl-CoA desaturase, a 53-kD enzyme containing a nonheme iron center. NADH and oxygen (Og) are required, as are two other proteins cytochrome 65 reductase (a 43-kD flavo-protein) and cytochrome 65 (16.7 kD). All three proteins are associated with the endoplasmic reticulum membrane. Cytochrome reductase transfers a pair of electrons from NADH through FAD to cytochrome (Figure 25.14). Oxidation of reduced cytochrome be, is coupled to reduction of nonheme Fe to Fe in the desaturase. The Fe accepts a pair of electrons (one at a time in a cycle) from cytochrome b and creates a cis double bond at the 9,10-posi-tion of the stearoyl-CoA substrate. Og is the terminal electron acceptor in this fatty acyl desaturation cycle. Note that two water molecules are made, which means that four electrons are transferred overall. Two of these come through the reaction sequence from NADH, and two come from the fatty acyl substrate that is being dehydrogenated. 

The iron of Hb must be maintained in the ferrous state ferric iron is reduced to the ferrous state by the action of an NADH-dependent methemoglobin reductase system involving cytochrome reductase and cytochrome b. ... 

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