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G R Welch

Publications and source records attributed to G R Welch.

66 records · Page 4Linked to original sources
PubMed1983

Protein fluctuation and enzyme activity.

The possible participation of protein fluctuation in enzyme activity is considered in this paper. Fluctuation is defined as vibrations, involving collective motion of a large number of atoms in protein molecules. Kinetic and thermodynamic aspects of protein fluctuation and enzyme-ligand interactions are discussed, paying special attention to the influence of electric fields and environmental microviscosity. A brief analysis of available experimental and theoretical data strongly suggests an interrelationship between protein fluctuation and enzyme function.

Enzymes↗
PubMed1983

Effect of viscosity on enzyme-ligand dissociation. II. Role of the microenvironment.

A theoretical treatment, describing a novel viscosity effect on decomposition of enzyme-ligand complexes, recently appeared (Somogyi et al., 1978). From this approach emerged a mechanistic picture of the manner in which increased viscosity lowers the value of the decomposition rate constant. A refined version of this model is presented herein. The analysis is extended to the molecular microenvironment ultimately responsible for mediating the "viscosity effect." Consideration is given to two major factors: (1) the role of viscosity in attenuating the excess chemical energy and (2) the statistical features of the microviscosity. In view of spatiotemporal inhomogeneity in the liquid structure, the concept of averaged microviscosity is introduced to parametrize the enzyme-ligand recombination probability. Quantitative predictions are consistent with models of liquid structure and with results from enzyme studies. The "viscosity effect" may contribute to substrate compartmentation in organized multi-enzyme systems in vivo.

Enzymes↗
PubMed1975

Influence of an aggregated multienzyme system on transient time: kinetic evidence for compartmentation by an aromatic-amino-acid synthesizing complex of Neurospora crassa.

The aromatic complex of Neurospora crassa is an aggregated multienzyme system which catalyzes five consecutive reactions in the central pathway leading to the biosynthesis of the aromatic amino acids. In an attempt to understand the physiological importance of this complex in particular, as well as the importance of cellular organization of enzyme systems in general, we have isolated the complex and have begun to characterize its catalytic properties. Optimum conditions for the assay of the overall 5-step reaction catalyzed by the partially purified complex have been determined. An analog computer was programmed to represent an unaggregated system of five enzymes with rate constants identical to those found for the constituent enzymes of the complex. By direct comparison, it was shown that the lags (transient times) obtained for the overall reaction were 10-15 times longer for the hypothetical unaggregated system than for the complex. We conclude from these data that the aggregated multienzyme system compartmentalizes intermediate substrates during the course of the overall reaction. We suggest that, in addition to "channeling" intermediates of competing pathways, reduction of the transient time may be an important consequence of the containment of intermediates within a physically associated enzyme sequence. The fact that the aromatic complex exhibits a second catalytic property unique to aggregated enzyme systems, "coordinate activation" [Welch, G.R. & Gaertner, F.H. (1975) Arch. Biochem. Biophys., in press] indicates that the physical association of these enzymes may have more than one physiological function.

Amino Acids↗
PubMed1971

Evidence for distinct kynureninase and hydroxykynureninase activities in Neurospora crassa.

Previous studies have indicated that a single enzyme, "kynureninase," catalyzes the reactions of l-kynurenine to anthranilate and l-3-hydroxykynurenine to 3-hydroxyanthranilate in Neurospora crassa and in other organisms. The present report describes separate enzymes which catalyze these reactions in N. crassa. The first, a kynureninase, preferentially catalyzes kynurenine to anthranilate and is induced over 400-fold by tryptophan or a catabolite of tryptophan. The second, a hydroxykynureninase, is constitutive or noninducible by tryptophan and preferentially catalyzes l-3-hydroxykynurenine to 3-hydroxyanthranilate. The physiological significance of these enzymes may be inferred from the facts that (i) the noninducible enzyme hydroxykynureninase appears to be the main enzyme present in uninduced cells that is capable of catalyzing l-3-hydroxykynurenine to 3-hydroxyanthranilate for the indispensible synthesis of nicotinamide adenine dinucleotide, and (ii) the inducible enzyme kynureninase is induced by tryptophan to a concentration far in excess of that needed to meet the requirements of the cells for nicotinamide adenine dinucleotide, resulting in the excretion of anthranilate into the medium.

Cell-Free System↗
PubMedDate not supplied

Energy coupling and Hill cycles in enzymatic processes.

We review how Hill's work on enzyme catalysis has nurtured our understanding of the mechanism by which enzymes can couple downhill processes to uphill processes. More specifically, we discuss the following questions: (i) Does it make sense to distinguish the chemical potential of the bound ligand from that of the binding enzyme? (ii) To what extent can free-energy transduction be localized at some crucial step in the catalytic cycle? (iii) Need enzymes be optimized so as to even out the profile of basic free energy along the catalytic cycle? (iv) How do continuous models of conformational transitions relate to discrete state diagrams and their kinetic elaborations? We conclude that (1) only in very special cases is it useful to designate a portion of the free energy of the enzyme-ligand complex as the free energy of the bound ligand; (2) only for some mechanisms can free-energy transduction be localized within a part of the catalytic cycle; (3) only in special cases should one expect enzymes to be "optimized" so as to have smooth basic free-energy profiles; and (4) transition rate constants can often be related to conformational diffusion constants, although in certain situations the kinetic description of an enzyme as if jumping between discrete states is impracticable; a diffusion-type description may then be preferable.

Catalysis↗