The biochemistry and medical significance of the flavonoids.

Flavonoids are plant pigments that are synthesised from phenylalanine, generally display marvelous colors known from flower petals, mostly emit brilliant fluorescence when they are excited by UV light, and are ubiquitous to green plant cells. The flavonoids are used by botanists for taxonomical classification. They regulate plant growth by inhibition of the exocytosis of the auxin indolyl acetic acid, as well as by induction of gene expression, and they influence other biological cells in numerous ways. Flavonoids inhibit or kill many bacterial strains, inhibit important viral enzymes, such as reverse transcriptase and protease, and destroy some pathogenic protozoans. Yet, their toxicity to animal cells is low. Flavonoids are major functional components of many herbal and insect preparations for medical use, e.g., propolis (bee's glue) and honey, which have been used since ancient times. The daily intake of flavonoids with normal food, especially fruit and vegetables, is 1-2 g. Modern authorised physicians are increasing their use of pure flavonoids to treat many important common diseases, due to their proven ability to inhibit specific enzymes, to simulate some hormones and neurotransmitters, and to scavenge free radicals.

Kinetic analysis of the transient phase and steady state of open multicyclic enzyme cascades.

This paper presents a kinetic analysis of the whole reaction course, i.e. of both the transient phase and the steady state, of open multicyclic enzyme cascade systems. Equations for fractional modifications are obtained which are valid for the whole reaction course. The steady state expressions for the fractional modifications were derived from the latter equations since they are not restricted to the condition of rapid equilibrium. Finally, the validity of our results is discussed and tested by numerical integration. Apart from the intrinsic value of knowing the kinetic behaviour of any of the species involved in any open multicyclic enzyme cascade, the kinetic analysis presented here can be the basis of future contributions concerning open multicyclic enzyme cascades which require the knowledge of their time course equations (e.g. evaluation of the time needed to reach the steady state, suggestion of kinetic data analysis, etc.), analogous to those already carried out for open bicyclic cascades.

Control of the pathogenic conformational change of the prion protein by an attractor of low order.

The molecular vibrations of the infectious part of the prion protein has been studied by the methods of nonlinear dynamics using NMR-data of the protein in solution to test a new hypothesis for the nature of the pathogenic isomerization. The result was that the conformational change accompanying the conversion of the physiological form (PrP(c)) to the pathological (PrP(Sc)) one displays the characteristic properties of an attractor of the dimension 2.7+/-0.2, whereas the dimensions of the C-terminal, potentially infectious half of the physiological and the pathological forms are 5.3+/-0.3 and 3.9+/-0.3, resp. A plot of the average RMS of the vibrations per atom of the amino acids along the peptide chain suggests a pivotal role of E(167) and D(196). The vibrations of these residues are strongly dampened by the pathogenic conformational change suggesting that the neutralization to the hydrophobic form facilitates the isomerisation. This observation lends credence to the hypothesis that the pathological conformational change is released by the charge neutralization of the abundant, basic side chains lining the cleft in PrP(c) by a pK-shift caused by a transient ion flux from an action potential or by an RNA ligand. The attractor ensures that only the two conformers PrP(c) and PrP(Sc)-monomer, which are switching the polyadenylation of mRNA for synaptic proteins on and off, prevail. Some xenogenic PrP(Sc) seem to have a tendency to polymerize irreversibly, which is likely to inhibit the translation, thus killing neurons. The autocorrelation function is dampened (long correlation length for the 3 cases), the Poincaré plot seems to show the cross-section of a dense attractor for PrP(Sc) and a loose one for PrP(c), the Lyapunov exponent is positive and the power spectrum is broad. The Hurst plots of PrP(Sc) and PcP(c) show monofractality. The attractor hypothesis offers a supplement, or an alternative, to the current, inconclusive ideas of the nature of the PrP isomerization. The identification of the control factors may permit the reversal of the fatal conformational change. The dynamic parameters were checked by the interpoint distance method of Judd and by an analysis of the Fourier-transformed data.