Oxidation of NADH by chloramines and chloramides and its activation by iodide and by tertiary amines

Irreversible oxidation of reduced nicotinamide nucleotides by neutrophil-derived halogen oxidants (HOCl, chloramines, HOBr, etc.) is likely to be a highly lethal process, because of the essential role of NAD(P)H in important cell functions such as mitochondrial electron transport, and control of the cellular thiol redox state by NADPH-dependent glutathione reductase. Chloramines (chloramine-T, NH(2)Cl, etc.) and N-chloramides (N-chlorinated cyclopeptides) react with NADH to generate the same products as HOCl, i.e., pyridine chlorohydrins, as judged from characteristic changes in the NADH absorption spectrum. Compared with the fast oxidation of NADH by HOCl, k approximately 3 x 10(5) M(-1) s(-1) at pH 7.2, the oxidation by chloramines is about five orders of magnitude slower; that by chloramides is about four orders of magnitude slower. Apparent rate constants for oxidation of NADH by chloramines increase with increasing proton or buffer concentration, consistent with general acid catalysis, but oxidation by chloramides proceeds with pH-independent kinetics. In presence of iodide the oxidation of NADH by chloramines or chloramides is faster by at least two orders of magnitude; this is due to reaction of iodide with the N-halogen to give HOI/I(2), the most reactive and selective oxidant for NADH among HOX species. Quinuclidine derivatives (QN) like 3-chloroquinuclidine and quinine are capable of catalyzing the irreversible degradation of NADH by HOCl and by chloramines; QN(+)Cl, the chain carrier of the catalytic cycle, is even more reactive toward NADH than HOCl/ClO(-) at physiological pH. Oxidation of NADH by NH(2)Br proceeds by fast, but complex, biphasic kinetics. A compilation of rate constants for interactions of reactive halogen species with various substrates is presented and the concept of selective reactivity of N-halogens is discussed.     

Evolutionary Distributions and Competition by Way of Reaction-Diffusion and by Way of Convolution

Evolution by natural selection is the most ubiquitous and well understood process of evolution. We say distribution instead of the distribution of the density of populations of phenotypes across the values of their adaptive traits. A phenotype refers to an organism that exhibits a set of values of adaptive traits. An adaptive trait is a trait that a phenotype exhibits where the trait is subject to natural selection. Natural selection is a process by which populations of different phenotypes decline at different rates. An evolutionary distribution (ED) encapsulates the dynamics of evolution by natural selection. The main results are: (i) ED are derived by way of PDE of reaction-diffusion type and by way of integro-differential equations. The latter capture mutations through convolution of a kernel with the rate of growth of a population. The kernel controls the size and rate of mutations. (ii) The numerical solution of a logistic-like ED driven by competition corresponds to a bounded traveling wave solution of population models based on the logistic. (iii) Competition leads to increase in diversity of phenotypes on a single ED. Diversity refers to change in the number of local maxima (minima) within the bounds of values of adaptive traits. (iv) The principle of competitive exclusion in the context of evolution depends, smoothly, on the size and rate of mutations. (v) We identify the sensitivity—with respect to survival—of phenotypes to changes in values of adaptive traits to be an important parameter: increase in the value of this parameter results in decrease in evolutionary-based diversity. (vi) Stable ED corresponds to Evolutionary Stable Strategy; the latter refers to the outcome of a game of evolution.     

Selective absorption and scattering of light by solutions of macromolecules and by particulate suspensions

For particulate suspensions and for solutions that scatter light measurably the total absorbance A generally contains contributions due to specific absorption (Aa) and scattering of light (As). The quantity As is closely related to the turbidity tau. In general, spectrophotometry of such systems requires proper modification of the spectrophotometer used in order to permit accurate determination of the absorbance A and of the derived quantities Aa and As. Apparent deviation from Beer's law in such systems is often due to inappropriate experimental technique. After a discussion of the parameters that determine the intensity of light scattered by solutes, an account is given of the experimental precautions to be taken for determination of the absorbance of light scattering suspensions and solutions and of techniques for correcting absorbance spectra for scattering of light. Measurement of the turbidity is briefly confronted with determination of the scattering ratio i90 degrees/Io and the impact of erroneous turbidity measurements on derived molecular parameters is discussed.     

Inhibition of the oxidation of acetaldehyde and formaldehyde by hepatocytes and mitochondria by crotonaldehyde

Crotonaldehyde was oxidized by disrupted rat liver mitochondrial fractions or by intact mitochondria at rates that were only 10 to 15% that of acetaldehyde. Although a poor substrate for oxidation, crotonaldehyde is an effective inhibitor of the oxidation of acetaldehyde by mitochondrial aldehyde dehydrogenase, by intact mitochondria, and by isolated hepatocytes. Inhibition by crotonaldehyde was competitive with respect to acetaldehyde, and the Ki for crotonaldehyde was about 5 to 20 microM. Crotonaldehyde had no effect on the oxidation of glutamate or succinate. Very low levels of acetaldehyde were detected during the metabolism of ethanol. Crotonaldehyde increased the accumulation of acetaldehyde more than 10-fold, indicating that crotonaldehyde, besides inhibiting the oxidation of added acetaldehyde, also inhibited the oxidation of acetaldehyde generated by the metabolism of ethanol. Formaldehyde was a substrate for the low-Km mitochondrial aldehyde dehydrogenase, as well as for a cytosolic, glutathione-dependent formaldehyde dehydrogenase. Crotonaldehyde was a potent inhibitor of mitochondrial oxidation of formaldehyde, but had no effect on the activity of formaldehyde dehydrogenase. In hepatocytes, crotonaldehyde produced about 30 to 40% inhibition of formaldehyde oxidation, which was similar to the inhibition produced by cyanamide. This suggested that part of the formaldehyde oxidation occurred via the mitochondrial aldehyde dehydrogenase, and part via formaldehyde dehydrogenase. The fact that inhibition by crotonaldehyde is competitive may be of value since other commonly used inhibitors of aldehyde dehydrogenase are irreversible inhibitors of the enzyme.     

Loss and recovery of excitability by normal and by degenerating nerves deprived of sodium

A study has been made of the loss of excitability in a sodium-free medium and of the recovery of excitability in Ringer's solution by A fibers of normal frog nerves and of nerves in advanced stages of Wallerian degeneration. With normal nerves that are being kept in a sodium-free medium the number of conducting fibers does not undergo a readily detectable decrease in less than 1 to 2 hours; inexcitability of all the A fibers does not develop in less than 7 to 8 hours. During the development of inexcitability the speed of conduction of the still conducting fibers undergoes a progressive decrease; in advanced stages the speed of conduction is not more than one-fifth of the normal speed. The nerve fibers lose the ability to conduct rhythmic trains of impulses earlier than the ability to conduct single impulses. The recovery of excitability in Ringer's solution duplicates in a reverse order the sequence of changes that have been previously observed during the development of inexcitability. The rate of the recovery of excitability in Ringer's solution is higher than the rate of the loss of excitability in the sodium-free medium. With degenerating nerves the effect of the lack of sodium develops qualitatively in the same manner in which it develops with normal nerves. Degenerating nerve fibers, however, become inexcitable in a sodium-free medium earlier than normal fibers. The recovery of the excitability in Ringer's solution takes place in much the same manner in normal and in degenerating nerve fibers. The loss of excitability during Wallerian degeneration is a process that develops simultaneously, or practically so, throughout the entire length of the fibers. The nerve fibers retain a great deal of functional ability throughout the several days which precede the onset of inexcitability and then suddenly become inexcitable.     

Comparison of food webs constructed by evolution and by immigration

We present results contrasting food webs constructed using the same model where the source of species was either evolution or immigration from a previously evolved species pool. The overall structure of the webs are remarkably similar, although we find some important differences which mainly relate to the percentage of basal and top species. Food webs assembled from evolved webs also show distinct plateaux in the number of tropic levels as the resources available to system increase, in contrast to evolved webs. By equating the resources available to basal species to area, we are able to examine the species–area curve created by each process separately. They are found to correspond to different regimes of the tri-phasic species–area curve.