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E L Sutton

Publications and source records attributed to E L Sutton.

3 recordsLinked to original sources
PubMed1998

A US military perspective.

This paper discusses lipid therapy decision-making at the population level within the United States (US) Military Health Services System. The US Military Health Services System serves approximately 8.2 million beneficiaries fairly representative of the general population. Of its $680 million annual pharmacy expenditure, $45-$50 million is spent on lipid-lowering drugs. The military Medical Treatment Facilities (MTF) carry a Tri-Service Drug Formulary list, which serves as a bare minimum to which individual facilities may add other agents. The Department of Defense Pharmacoeconomic Center (PEC) performs cost-effectiveness analyses, establishes the Tri-Service Drug Formulary list and the National Mail Order Pharmacy formulary list, and provides drug treatment guidelines. Hyperlipidemia treatment guidelines published by the Pharmacoeconomic Center in 1995, which recommend the use of niacin, colestipol, and pravastatin, are currently under revision to take into consideration new drugs and new information in the field of lipid-lowering therapies. Future changes to the MTF outpatient formulary management may include the introduction of a Basic Core List of essential agents and a Master Pharmaceutical Agent List comprising the only drugs from which facilities may choose to add to their Basic Core List. These changes are designed to standardize drug availability across military facilities to leverage market share for lower drug prices.

Journal Article↗
PubMed1986

Reaction energetics of a mutant triosephosphate isomerase in which the active-site glutamate has been changed to aspartate.

The essential catalytic base at the active site of the glycolytic enzyme triosephosphate isomerase is the carboxylate group of Glu-165, which directly abstracts either the 1-pro-R proton of dihydroxyacetone phosphate or the 2-proton of (R)-glyceraldehyde 3-phosphate to yield the cis-enediol intermediate. Using the methods of site-directed mutagenesis, we have replaced Glu-165 by Asp. The three enzymes chicken isomerase from chicken muscle, wild-type chicken isomerase expressed in Escherichia coli, and mutant (Glu-165 to Asp) chicken isomerase expressed in E. coli have each been purified to homogeneity. The specific catalytic activities of the two wild-type isomerases are identical, while the specific activity of the mutant enzyme is reduced by a factor of about 1000. The observed kinetic differences do not derive from a change in mechanism in which the aspartate of the mutant enzyme acts as a general base through an intervening water molecule, because the D2O solvent isotope effects and the stoichiometries of inactivation with bromohydroxyacetone phosphate are identical for the wild-type and mutant enzymes. Using the range of isotopic experiments that were used to delineate the free-energy profile of the wild-type chicken enzyme, we here derive the complete energetics of the reaction catalyzed by the mutant protein. Comparison of the reaction energetics for the wild-type and mutant isomerases shows that only the free energies of the transition states for the two enolization steps have been seriously affected. Each of the proton abstraction steps is about 1000-fold slower in the mutant enzyme. Evidently, the excision of a methylene group from the side chain of the essential glutamate has little effect on the free energies of the intermediate states but dramatically reduces the stabilities of the transition states for the chemical steps in the catalyzed reaction.

Aspartic Acid↗