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Coordinate activation of a multienzyme complex by the first substrate. Evidence for a novel regulatory mechanism in the polyaromatic pathway of Neurospora crassa

Journal Article · · Arch. Biochem. Biophys.; (United States)

The catalytic efficiencies of four of the five enzymes of the aromatic complex of Neurospora crassa were significantly increased by incubation with the first substrate, 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP). Activation with DAHP was accomplished independently of catalysis by incubating the purified enzyme system in a mixture devoid of requisite cofactors and intermediate substrates. The activity of each enzyme in the complex was subsequently assayed in appropriate complete reaction mixtures. Double-reciprocal plots of the kinetic data were used to determine the effect of DAHP on the catalytic constants of each enzyme. The results for five enzymes, dehydroquinate synthase, dehydroquinase, dehydroshikimate reductase, shikimate kinase, and enolpyruvylshikimate phosphate synthase, were as follows. Incubated in the absence of DAHP (i.e. unactivated) the maximal velocities (V) in relative units were 1, 20, 4, 2, and 5, respectively, and the K/sub m/ values were 0.06, 0.1, 0.04, 0.1, and 0.1 mM for the respective substrates. In direct comparison, when the complex was incubated with DAHP (i.e. activated), the V values were 2, 20, 4, 2, and 5 and the K/sub m/ values were approx.0.01, 0.02, 0.02, 0.1, and 0.02 mM. The concentration of DAHP required for half-maximal activation in each case was approximately 1.0 mM. This suggests but does not prove that a single site, distinct from the catalytic site, is responsible for the coordinate activation. We propose that the physiological importance of the activation involves a novel regulatory device that provides a means for directing the flow of aromatic intermediates from the anabolicpolyaromatic route to a catabolic one in response to the energy charge of the cell. In support of this view are the facts that shikimate kinase was found to be inhibited by ADP and that, as a result of the activation of the other four enzymes in the complex, shikimate kinase becomes rate limiting and catalyzes a nonequilibrium reaction.

Research Organization:
Oak Ridge National Lab., TN
OSTI ID:
7332168
Journal Information:
Arch. Biochem. Biophys.; (United States), Journal Name: Arch. Biochem. Biophys.; (United States) Vol. 172; ISSN ABBIA
Country of Publication:
United States
Language:
English