Topa, formation

The results were further confirmed by resonance Raman spectrometry on comparing the spectra of phenylhydrazone and p-nitrophenylhydrazone of bovine plasma amine oxidase with the derivatized pentapeptides of the active site and the model compound. All these spectra showed great similarity in position (wavenumber) and spectral band intensity, while the spectrum of a PQQ model compound differed markedly [45]. Similar experiments confirmed the presence of topa quinone in porcine kidney, pea seedling and Arthrobacter PI amine oxidases. Moreover, the experimental data obtained for intact enzymes excluded the possibility of an artificial topa quinone formation during the proteolysis and peptide isolation [45]. 

Fig. (3). Mechanism of the substrate oxidation by copper amine oxidases [29]. The scheme shows the roles of copper, topa quinone cofactor and proton abstracting base (Asp) in the catalytic cycle. The oxidized enzyme (a) reacts with an amine substrate giving a Schiff base formation at C-5 of the TPQ (b-c), followed by proton abstraction (d). After hydrolysis and release of the aldehyde, an aminoresorcinol species is formed (e), and the reduced cofactor is reoxidized by molecular oxygen via Cu(I)-semiquinone intermediate (/).

Autocatalytic formation of topa quinone in prokaryotic copper amine oxidases has already been demonstrated several times in vitro. Escherichia coli K-12 produced almost inactive amine oxidase after... 

Hyperuricemia in Lotta Topa ne s case arose as a consequence of over-j production of uric acid. Treatment with allopurinol not only inhibits xan-thine oxidase, lowering the formation of uric acid with an increase in the excretion of hypoxanthine and xanthine, but also decreases the overall synthesis of purine nucleotides. Hypoxanthine and xanthine produced by purine degradation are salvaged (i.e., converted to nucleotides) by a process that requires the consumption of PRPP. PRPP is a substrate for the glutamine phosphoribosyl amidotransferase reaction that initiates purine biosynthesis. Because the normal cellular levels of PRPP and glutamine are below the of the enzyme, changes in the level of either substrate can accelerate or reduce the rate of the reaction. Therefore, decreased levels of PRPP cause decreased synthesis of purine nucleotides. 

The biosynthesis of tunichromes is not yet fully understood, but it seems likely that these compounds are formed by the degradation of polymers of DOPA and TOPA obtained by ribosomal synthesis. Several labeling experiments have shown that phenylalanine and tyrosine are incorporated in vivo in tunichrome An-1 of Ascidia cerat-odes, the only tunichrome present in this species (He et al, 1992 Robinson et al, 1996). Figure 28.34 summarizes a hypothesis that explains the formation of tunichromes Pm-1 and An-1. 

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