The present study describes the enzymatic properties and molecular identification of 5'-nucleotidase in soluble and microsomal fractions from rat cardiac ventricles. Using AMP as a substrate, the results showed that the cation and the concentration required for maximal activity in the two fractions was magnesium at a final concentration of 1 mM. The pH optimum for both fractions was 9.5. The apparent K(m) (Michaelis constant) values calculated from the Eadie-Hofstee plot were 59.7+/-10.4 microM and 134.8+/-32.1 microM, with V(max) values of 6.7+/-0.4 and 143.8+/-23.8 nmol P(i)/min/mg of protein (means+/-S.D., n=4) from soluble and microsomal fractions respectively. Western blotting analysis of ecto-5'-nucleotidase revealed a 70 kDa protein in both fractions, with the major proportion present in the microsomal fraction. The presence of these enzymes in the heart probably has a physiological function in adenosine signalling. Furthermore, the presence of ecto-5'-nucleotidase in the microsomal fraction could have a role in the modulation of the excitation-contraction-coupling process through involvement of the Ca(2+) influx into the sarcoplasmic reticulum. The measurement of maximal enzyme activities in the two fractions highlights the potential capacity of the different pathways of purine metabolism in the heart.
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http://dx.doi.org/10.1042/BSR20070039 | DOI Listing |
Eur J Med Chem
February 2025
Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, 63110, USA; Center for Clinical Pharmacology, Washington University School of Medicine and University of Health Sciences and Pharmacy, St. Louis, Missouri, 63110, USA; Department of Pharmaceutical and Administrative Sciences, University of Health Sciences and Pharmacy, St. Louis, Missouri, 63110, USA. Electronic address:
Inhibition of mitochondrial pyruvate transport via the mitochondrial pyruvate carrier (MPC) has shown beneficial effects in treating metabolic diseases, certain cancers, various forms of neurodegeneration, and hair loss. These benefits arise either from the direct inhibition of mitochondrial pyruvate metabolism or from the metabolic rewiring when pyruvate entry is inhibited. However, current MPC inhibitors are either nonspecific or possess poor pharmacokinetic properties.
View Article and Find Full Text PDFArch Pharm (Weinheim)
January 2025
Department of Pharmacy, University of Salerno, Fisciano, Italy.
Inhibiting microsomal prostaglandin E synthase-1 (mPGES-1), an inducible enzyme involved in prostaglandin E (PGE) biosynthesis and tumor microenvironment (TME) homeostasis, is a valuable strategy for treating inflammation and cancer. In this work, 5-methylcarboxamidepyrrole-based molecules were designed and synthesized as new compounds targeting mPGES-1. Remarkably, compounds 1f, 2b, 2c, and 2d were able to significantly reduce the activity of the isolated enzyme, showing IC values in the low micromolar range.
View Article and Find Full Text PDFACS Med Chem Lett
December 2024
Center for the Research and Advancement in Fragments and Molecular Targets (CRAFT), Faculdade de Ciências Farmaceuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo 05508-070, Brazil.
The SARS-CoV-2 pandemic has significantly challenged global public health, highlighting the need for effective therapeutic options. This study focuses on the papain-like protease (PLpro) of SARS-CoV-2, which is a critical enzyme for viral polyprotein processing, maturation, and immune evasion. We employed a combined approach that began with computational models in a virtual screening campaign, prioritizing compounds from our in-house chemical library against PLpro.
View Article and Find Full Text PDFEur J Med Chem
February 2025
School of Pharmacy, Fudan University, Shanghai, 201203, China; School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, 453007, China. Electronic address:
J Med Chem
December 2024
Instituto Nacional de Ciência e Tecnologia em Tuberculose, Centro de Pesquisas em Biologia Molecular e Funcional, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul 90616-900, Brazil.
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