Joseph W. DePierre

Bio: Joseph W. DePierre is an academic researcher from Stockholm University. The author has contributed to research in topics: Epoxide hydrolase & Peroxisome. The author has an hindex of 45, co-authored 204 publications receiving 10738 citations.

Enzyme topology of intracellular membranes

Abstract: PERSPECTIVES AND SUMMARY 202 INTRODUCTION 203 Contemporary Concepts of Membrane Structure 204 Methodology for Studying the Topology of Membranes ... ........ 205 Enzyme topology in the lateral plane ...... 205 Enzyme topology in the transverse plane ........ 206 Lipid topology .... ..... ....... ...... ........ 206 Other methods ......... ......... ....... ... ... ... ..... ... 207 MITOCHONDRIA 207 Morphology 207 The Outer Membrane ......... 207 The Inner Membrane 209 General features ...... ...... ... ...... ... ..... ..... ........ 209 General aspects of lateral topology ...... ........ ...... 210 General aspects of transverse topology ........ ........ ........ 212 The respiratory chain, ATPase, and related energy-transducing systems 214 General features 214 NADH-Q reductase (Camp/ex I) 215 Succinate-Q reductase (Complex II) 217 Ubiquinone ... ..... ....... ...... ..... 218 QHrcytochrome c reductase (Complex III) .... 220 Cytochrome c .... ..... ....... ....... ...... 221 Cytochrome c oxidase (Comp/ex IV) 222 Transhydrogenase .. ..... ..... ..... .... ... ......... ... ... ....... ... ... ........ .... 226 ATPase 227 Ion trans/ocators ... ... ... ........ ... ... ..... 229 Other enzymes . ........ ..... ... ......... ... ... ... ...... .... 230

Microsomal glutathione transferase. Purification in unactivated form and further characterization of the activation process, substrate specificity and amino acid composition.

Abstract: The procedure developed for purification of the N-ethylmaleimide-activated microsomal glutathione transferase was applied successfully to isolation of this same enzyme in unactivated form. The microsomal glutathione transferases, the unactivated and activated forms, were shown to be identical in terms of molecular weight, immunochemical properties, and amino acid composition. In addition the microsomal glutathione transferase purified in unactivated form could be activated 15-fold with N-ethylmaleimide to give the same specific activity with 1-chloro-2,4-dinitrobenzene as that observed for the enzyme isolated in activated form. This activation involved the binding of one molecule N-ethylmaleimide to the single cysteine residue present in each polypeptide chain of the enzyme, as shown by amino acid analysis, determination of sulfhydryl groups by 2,2'-dithiopyridyl and binding of radioactive N-ethylmaleimide. Except for the presence of only a single cysteine residue and the total absence of tryptophan, the amino acid composition of the microsomal glutathione transferase is not remarkable. The contents of aspartic acid/asparagine + glutamic acid/glutamine, of basic amino acids, and of hydrophobic amino acids are 15%, 12% and 54% respectively. The isoelectric point of the enzyme is 10.1. Microsomal glutathione transferase conjugates a wide range of substrates with glutathione and also demonstrates glutathione peroxidase activity with cumene hydroperoxide, suggesting that it may be involved in preventing lipid peroxidation. Of the nine substrates identified here, the enzymatic activity towards only two, 1-chloro-2,4-dinitrobenzene and cumene hydroperoxide, could be increased by treatment with N-ethylmaleimide. This treatment results in increases in both the apparent Km values and V values for 1-chloro-2,4-dinitrobenzene and cumene hydroperoxide. Thus, although clearly distinct from the cytosolic glutathione transferases, the microsomal enzyme shares certain properties with these soluble enzymes, including a relative abundance, a high isoelectric point and a broad substrate specificity. The exact role of the microsomal glutathione transferase in drug metabolism, as well as other possible functions, remains to be established.

The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance.

Abstract: The glutathione S-transferases (GST) represent a major group of detoxification enzymes. All eukaryotic species possess multiple cytosolic and membrane-bound GST isoenzymes, each of which displays distinct catalytic as well as noncatalytic binding properties: the cytosolic enzymes are encoded by at least five distantly related gene families (designated class alpha, mu, pi, sigma, and theta GST), whereas the membrane-bound enzymes, microsomal GST and leukotriene C, synthetase, are encoded by single genes and both have arisen separately from the soluble GST. Evidence suggests that the level of expression of GST is a crucial factor in determining the sensitivity of cells to a broad spectrum of toxic chemicals. In this article the biochemical functions of GST are described to show how individual isoenzymes contribute to resistance to carcinogens, antitumor drugs, environmental pollutants, and products of oxidative stress.A description of the mechanisms of transcriptional and posttranscriptional regulat...

Glutathione transferases--structure and catalytic activity.

Abstract: The glutathione transferases are recognized as important catalysts in the biotransformation of xenobiotics, including drugs as well as environmental pollutants. Multiple forms exist, and numerous transferases from mammalian tissues, insects, and plants have been isolated and characterized. Enzymatic properties, reactions with antibodies, and structural characteristics have been used for classification of the glutathione transferases. The cytosolic mammalian enzymes could be grouped into three distinct classes--Alpha, Mu, and Pi; the microsomal glutathione transferase differs greatly from all the cytosolic enzymes. Members of each enzyme class have been identified in human, rat, and mouse tissues. Comparison of known primary structures of representatives of each class suggests a divergent evolution of the enzyme proteins from a common precursor. Products of oxidative metabolism such as organic hydroperoxides, epoxides, quinones, and activated alkenes are possible "natural" substrates for the glutathione transferases. Particularly noteworthy are 4-hydroxyalkenals, which are among the best substrates found. Homologous series of substrates give information about the properties of the corresponding binding site. The catalytic mechanism and the active-site topology have been probed also by use of chiral substrates. Steady-state kinetics have provided evidence for a "sequential" mechanism.

The functions and regulation of glutathione s-transferases in plants.

Abstract: ▪ Abstract Glutathione S-transferases (GSTs) play roles in both normal cellular metabolism as well as in the detoxification of a wide variety of xenobiotic compounds, and they have been intensively studied with regard to herbicide detoxification in plants. A newly discovered plant GST subclass has been implicated in numerous stress responses, including those arising from pathogen attack, oxidative stress, and heavy-metal toxicity. In addition, plant GSTs play a role in the cellular response to auxins and during the normal metabolism of plant secondary products like anthocyanins and cinnamic acid. This review presents the current knowledge about the functions of GSTs in regard to both herbicides and endogenous substrates. The catalytic mechanism of GST activity as well as the fate of glutathione S-conjugates are reviewed. Finally, a summary of what is known about the gene structure and regulation of plant GSTs is presented.