Paul A. M. Michels
University of Edinburgh
Publications 288
#1Emmanuel Oluwadare Balogun (ABU: Ahmadu Bello University)H-Index: 7
#2Daniel Ken Inaoka (Nagasaki University)H-Index: 11
Last.Kiyoshi Kita (Nagasaki University)H-Index: 46
view all 18 authors...
African trypanosomiasis, sleeping sickness in humans or nagana in animals, is a potentially fatal neglected tropical disease and a threat to 65 million human lives and 100 million small and large l...
#2Citlali VázquezH-Index: 3
Last.Emma SaavedraH-Index: 13
view all 10 authors...
Abstract Trypanothione (T(SH) 2 ) is the main antioxidant metabolite for peroxide reduction in Trypanosoma cruzi ; therefore, its metabolism has attracted attention for therapeutic intervention against Chagas disease. To validate drug targets within the T(SH) 2 metabolism, the strategies and methods of Metabolic Control Analysis and kinetic modeling of the metabolic pathway were used here, to identify the steps that mainly control the pathway fluxes and which could be appropriate sites for thera...
#1W. Zhong (Singapore–MIT alliance)H-Index: 2
#2Jingjing Guo (NAU: Nanjing Agricultural University)
Last.Peter C. Dedon (MIT: Massachusetts Institute of Technology)H-Index: 48
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Abstract In response to the stress of infection, Mycobacterium tuberculosis (Mtb) reprograms its metabolism to accommodate nutrient and energetic demands in a changing environment. Pyruvate kinase (PYK) is an essential glycolytic enzyme in the phosphoenolpyruvate–pyruvate–oxaloacetate node that is a central switch point for carbon flux distribution. Here we show that the competitive binding of pentose monophosphate inhibitors or the activator glucose 6-phosphate (G6P) to MtbPYK tightly regulates...
Abstract Entamoeba histolytica has neither Krebs cycle nor oxidative phosphorylation activities; therefore, glycolysis is the main pathway for ATP supply and provision of carbon skeleton precursors for the synthesis of macromolecules. Glucose is metabolized through fermentative glycolysis, producing ethanol as its main end-product as well as some acetate. Amoebal glycolysis markedly differs from the typical Embden-Meyerhof-Parnas pathway present in human cells: (i) by the use of inorganic pyroph...
2 CitationsSource
#1Héctor Acosta (University of Los Andes)H-Index: 7
#2Richard Burchmore (Glas.: University of Glasgow)H-Index: 34
Last.Wilfredo Quiñones (University of Los Andes)H-Index: 13
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Abstract In Trypanosoma cruzi, the causal agent of Chagas disease, the first seven steps of glycolysis are compartmentalized in glycosomes, which are authentic but specialized peroxisomes. Besides glycolysis, activity of enzymes of other metabolic processes have been reported to be present in glycosomes, such as β-oxidation of fatty acids, purine salvage, pentose-phosphate pathway, gluconeogenesis and biosynthesis of ether-lipids, isoprenoids, sterols and pyrimidines. In this study, we have puri...
3 CitationsSource
#1Peter M Fernandes (Edin.: University of Edinburgh)H-Index: 3
#2James Kinkead (Edin.: University of Edinburgh)H-Index: 1
Last.Malcolm D. Walkinshaw (Edin.: University of Edinburgh)H-Index: 50
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Eukaryotic ATP-dependent phosphofructokinases (PFKs) are often considered unidirectional enzymes catalysing the transfer of a phospho moiety from ATP to fructose 6-phosphate (F6P) to produce ADP and fructose 1,6-bisphosphate (F16BP). The reverse reaction is not generally considered to occur under normal conditions and has never been demonstrated for any eukaryotic ATP-dependent PFKs, though it does occur in PPi-dependent PFKs and has been experimentally shown for bacterial ATP-dependent PFKs. Ev...
#1Alice Rose Mitchell (Edin.: University of Edinburgh)H-Index: 1
#2Meng Yuan (Edin.: University of Edinburgh)H-Index: 3
Last.Malcolm D. Walkinshaw (Edin.: University of Edinburgh)H-Index: 50
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We show here that the M2 isoform of human pyruvate kinase (M2PYK) is susceptible to nitrosation and oxidation, and that these modifications regulate enzyme activity by preventing the formation of the active tetrameric form. The biotin-switch assay carried out on M1 and M2 isoforms showed that M2PYK is sensitive to nitrosation and that Cys326 is highly susceptible to redox modification. Structural and enzymatic studies have been carried out on point mutants for three cysteine residues (Cys424, Cy...
2 CitationsSource
#1Emma SaavedraH-Index: 13
Last.Paul A. M. Michels (Edin.: University of Edinburgh)H-Index: 50
view all 4 authors...
2 CitationsSource
#1Meng Yuan (Edin.: University of Edinburgh)H-Index: 3
#2Iain W. McNae (Edin.: University of Edinburgh)H-Index: 21
Last.Malcolm D. Walkinshaw (Edin.: University of Edinburgh)H-Index: 50
view all 9 authors...
We have tested the effect of all 20 proteinogenic amino acids on the activity of the M2 isoenzyme of pyruvate kinase (M2PYK) and show that, within physiologically relevant concentrations, phenylalanine, alanine, tryptophan, methionine, valine, and proline act as inhibitors, while histidine and serine act as activators. Size exclusion chromatography has been used to show that all amino acids, whether activators or inhibitors, stabilise the tetrameric form of M2PYK. In the absence of amino-acid li...
9 CitationsSource