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Biomedical subjects

F M Menger

Publications and source records attributed to F M Menger.

4 recordsLinked to original sources
PubMed1992

Analysis of ground-state and transition-state effects in enzyme catalysis.

"The entire and sole source of catalytic power is the stabilization of the transition state; reactant-state interactions are by nature inhibitory and only waste catalytic power". So reads a literature quote expressing the current view on enzyme catalysis proposed by Pauling over 40 years ago. Its validity is now examined by means of a "split-site" model in which an active site is subdivided into a region of binding and a region of reaction. Analysis of the resulting free energy levels clarifies several points of confusion regarding the nature of enzyme catalysis, including why enzyme/substrate complexes form if, indeed, they only "waste catalytic power". Circumstances are defined in which an evolving enzyme can both lower Km (i.e., enhance substrate binding) and improve the forward catalytic rate while never meddling with the transition structure at the reactive site. It is argued that this process is most advantageously viewed as a substrate destabilization embodying "conserved" interactions at the binding region. Classical transition-state stabilization and an "anti-Pauling" effect are both capable of inducing rate accelerations. In certain circumstances, the latter can predominate as it does with many enzyme-like intramolecular reactions. Behavioral modes discussed herein are applicable to the chemistry of catalytic host/guest and enzyme systems.

Catalysis↗
PubMed1991

Evidence for the regulation of the activity of protein kinase C through changes in membrane properties.

We measured the effects of two branched-chain analogs of distearoyl-phosphatidylcholine, containing either a methyl or an n-butyl group at the 8 position, on the bilayer to hexagonal phase transition temperature of dielaidoylphosphatidylethanolamine. The former compound raised the bilayer to hexagonal phase transition temperature while the latter compound lowered it. The opposite effects of these amphiphiles on protein kinase C activity (inhibition and activation, respectively) correlated with their effects on lipid polymorphism. Because of the similarity of the structures of these two compounds, it seems likely that their opposite effects on the activity of protein kinase C is a result of their alteration of the lipid environment of the membrane rather than to binding to a specific site on the protein. We also compared the effects of hexachlorophene on lipid polymorphism and protein kinase C activity at high and at low calcium concentrations. We also found that the effect of hexachlorophene forming a complex with Ca2+ is to increase both the hexagonal phase forming propensity of the membrane as well as to increase the activity of protein kinase C, again demonstrating the correlation between lipid phase propensity and effects on protein kinase C activity.

Animals↗