Uncoupling oxidase pathway

The third uncoupling pathway, or branch point, occurs at the Compound I species VII. If the substrate is bound too far away from the Compound I oxygen, or if the functional group closest to this oxygen is inert to oxidation, the hfetime of VII will be increased and electron-transfer reduction of VII to II can become the dominant reaction. The overall result is the use of two molecules of NAD(P)H to reduce O2 to two water molecules. This is the reaction catalyzed by oxidases and this oxidase uncouphng pathway has been... 

The substrate dependence of the oxidase uncoupling chatmel in CYP3A4 provided more information about productive and non-productive pathways and the role of the lipid bilayer in the overall efficiency of TST hydroxylation [310]. 

This transfer of electrons from cytochrome a to cytochrome aa would be the step in this pathway that is inhibited by cyanide. It should be kept in mind that Dicumarol not only uncouples phosphorylation and oxidation by acting in the electron transport chain at the site of phosphorylation corresponding to the position of vitamin K in the electron transport chain, but Dicumarol is also active at the site of phosphorylation at the level of cytochrome oxidase. 

Figure 3.2 Beneficial effects of folic acid on vascular wall. Folic acid circulates in human body as 5-methyltetrahydrofolate (5-MTHF). 5-MTHF lowers circulating homocysteine (Hey) levels, thus reducing systemic oxidative stress and Hcy-induced activation of prothrombotic mechanisms. In addition, vascular 5-MTHF has a favourable effect on intracellular Hey metabolism, attenuating Hcy-induced activation of NADPH oxidase isoforms (NOXs) in the vascular wall. Furthermore vascular 5-MTHF scavenges per se peroxynitrite (ONOO ) radicals in the vascular wall preventing the oxidation of vascular tetrahydrobiopterin (BH4) associated with endothelial nitric oxide synthase (eNOS) uncoupling and diminished vascular nitric oxide (NO) bioavailability. In total through these effects 5-MTHF lowers vascular oxidative and nitrosative stress. Thus by modulating vascular redox, 5-MTHF inhibits activation of proinffammatory pathways which orchestrate vascular wall inflammation and perpetuate endothelial dysfunction and atherogenesis development (unpublished).

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