Moskovitz J, Du F, Bowman CF, Yan SS. Methionine sulfoxide reductase A affects -amyloid solubility and mitochondrial function in a mouse model of Alzheimer’s disease. Am J Physiol Endocrinol Metab 310: E388–E393, 2016. First published January 19, 2016; doi:10.1152/ajpendo.00453.2015.—Accumulation of oxidized proteins, and especially -amyloid (A ), is thought to be one of the common causes of Al...

Zr-monosubstituted Lindqvist-type polyoxometalates (Zr-POMs), (Bu4N)2[W5O18Zr(H2O)3] (1) and (Bu4N)6[{W5O18Zr(μ-OH)}2] (2), have been employed as molecular models to unravel the mechanism of hydrogen peroxide activation over Zr(IV) sites. Compounds 1 2 are hydrolytically stable catalyze epoxidation C═C bonds in unfunctionalized alkenes α,β-unsaturated ketones, well sulfoxidation thioethers. Mon...

Background/aim: The in-vitro microsomal metabolism of (S)-3-((2,4,6-trimethylphenyl)thio)-4-(4-fluorophenyl)-5-(1-(6-methoxynaphtalene-2-yl)ethyl)-4H-1,2,4-triazole (SGK636), an anticancer drug candidate was studied using pig preparations fortified with NADPH to identify the potential S-oxidation and S-dealkylation metabolites.
 Materials methods: In present study, sulfoxide metabolite syn...

In vitro studies were conducted to identify the hepatic cytochrome P450 (CYP) forms involved in the oxidative metabolism of [14C]ABT-761 and its N-dehydroxylated metabolite, [14C]ABT-438, by human liver microsomes. The two compounds were metabolized by parallel pathways, to form the corresponding methylene bridge hydroxy metabolites. There was no evidence of sulfoxidation and/or ring hydroxylat...

Heme and nonheme monoxygenases and dioxygenases catalyze important oxygen atom transfer reactions to substrates in the body. It is now well established that the cytochrome P450 enzymes react through the formation of a high-valent iron(IV)-oxo heme cation radical. Its precursor in the catalytic cycle, the iron(III)-hydroperoxo complex, was tested for catalytic activity and found to be a sluggish...

It is a long-standing mechanistic consensus that the mutation of the proton-shuttle mediator Threonine (T) in Cytochrome P450 enzymes severs the water channel and thereby quenches the formation of the active species: the high-valent iron(IV)-oxo porphyrin p-cation radical species, compound I (Cpd I). Using MD simulations and hybrid QM/MM calculations of P450BM3 we demonstrate that this is not t...

ApoA-I and apoC-II are eluted in two isoforms and apoC-III2 is eluted in three isoforms by reversed phase high performance liquid chromatography (HPLC). The structural basis of these nongenetic heterogeneities was unravelled using HPLC of proteolytic peptides and time-of-flight secondary ion mass spectrometry (TOF-SIMS). In apoA-I, the chromatographic microheterogeneity was caused by the format...

Addition of anionic donors to the manganese(V)-oxo corrolazine complex Mn(V)(O)(TBP8Cz) has a dramatic influence on oxygen-atom transfer (OAT) reactivity with thioether substrates. The six-coordinate anionic [Mn(V)(O)(TBP8Cz)(X)](-) complexes (X = F(-), N3(-), OCN(-)) exhibit a ∼5 cm(-1) downshift of the Mn-O vibrational mode relative to the parent Mn(V)(O)(TBP8Cz) complex as seen by resonance ...