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H Kacser

Publications and source records attributed to H Kacser.

9 recordsLinked to original sources
PubMed1992

A strategy for increasing an in vivo flux by genetic manipulations. The tryptophan system of yeast.

Decreases in enzyme activity often have little effect on the flux carried by the pathway. Similarly, up-modulation of single genes, and hence of the dependent enzyme concentrations, is frequently found to be ineffective in increasing the flux in the pathway in which the enzyme occurs. This insensitivity to enzyme variation is demonstrated experimentally for five separate enzymes in the tryptophan synthesis system of yeast, first by down-modulation of the gene dose and secondly by increasing the dose using multi-copy vectors. Such a lack of response is discussed in terms of the concepts of metabolic control analysis. When these five enzymes, however, were simultaneously increased by a multi-copy vector carrying all five genes, a substantial elevation of the flux to tryptophan was observed. These findings revealed a new phenomenon, namely the more than additive effects on the flux of simultaneous elevations of several enzyme activities.

Down-Regulation↗
PubMed1990

Control analysis of transition times in metabolic systems.

The transition time, tau, of a metabolic system is defined as the ratio of the metabolite concentrations in the system, sigma, to the steady-state flux, J. Its value reflects a temporal characteristic of the system as it relaxes towards the steady state. Like other systemic properties, the value of tau will be a function of the enzyme activities in the system. The influence of a particular enzyme activity on tau can be quantified by a Control Coefficient, C tau ei. We show that it is possible to derive a Summation Theorem sigma ni = 1 C tau ei = -1 and a Connectivity Theorem sigma ni = 1 C tau ei.epsilon viSk = -Sk/sigma. We establish a 'sign rule' that predicts the order of positive and negative Control Coefficients in a sequence.

Enzymes↗
PubMed1978

Genetic variation in activity of the enzymes of glycolysis and gluconeogenesis between inbred strains of mice.

Variation in the activity of 21 liver and 15 erythrocyte enzymes between seven inbred strains of mice has been studied in a single area of metabolism, glycolysis and gluconeogenesis. Most of the variation between the strains is genetic. From the variation within and between inbred strains heritabilities (H2) were determined. Out of 35, 26 showed significant values above 0.4. A comparison with previously published work suggests that enzyme activities have mainly dominance and interaction components of variance, and this is discussed in relation to the variation in quantitative characters such as growth. In nine of the pairwise comparisons of the strains, the activity of the enzyme varied more than two-fold. In these cases the genetics and biochemistry of the enzyme was studied; F2 progeny were produced and assessed for segregation, and the heat stability of the enzyme was determined. No unequivocal segregation was observed, although in one case we found a considerable difference in heat stability. The variations found were not considered to be great enough to be useful as models of human inborn errors of metabolism or to study metabolic control. If such variants are to be found, sources of variation other than inbred strains must be used.

Animals↗