title: Effects of alpha-ketoglutarate on neutrophil intracellular amino and alpha-keto acid profiles and ROS production.
abstract: The aim of this study was to determine the effects of alpha-ketoglutarate on neutrophil (PMN), free alpha-keto and amino-acid profiles as well as important reactive oxygen species (ROS) produced [superoxide anion (O(2) (-)), hydrogen peroxide (H(2)O(2))] and released myeloperoxidase (MPO) activity. Exogenous alpha-ketoglutarate significantly increased PMN alpha-ketoglutarate, pyruvate, asparagine, glutamine, asparatate, glutamate, arginine, citrulline, alanine, glycine and serine in a dose as well as duration of exposure dependent manner. Additionally, in parallel with intracellular alpha-ketoglutarate changes, increases in O(2) (-) formation, H(2)O(2)-generation and MPO activity have also been observed. We therefore believe that alpha-ketoglutarate is important for affecting PMN "susceptible free amino- and alpha-keto acid pools" although important mechanisms and backgrounds are not yet completely explored. Moreover, our results also show very clearly that changes in intragranulocytic alpha-ketoglutarate levels are relevant metabolic determinants in PMN nutrition considerably influencing and modulating the magnitude and quality of the granulocytic host defense capability as well as production of ROS.
authors.affiliation: Clinics of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Giessen and Marburg GmbH, Justus-Liebig-University Giessen, Giessen, Germany. joerg.muehling@chiru.med.uni-giessen.de
authors.forename: Jörg
authors.initials: J
authors.lastname: Mühling
authors.forename: F
authors.initials: F
authors.lastname: Tussing
authors.forename: K A
authors.initials: KA
authors.lastname: Nickolaus
authors.forename: R
authors.initials: R
authors.lastname: Matejec
authors.forename: M
authors.initials: M
authors.lastname: Henrich
authors.forename: H
authors.initials: H
authors.lastname: Harbach
authors.forename: M
authors.initials: M
authors.lastname: Wolff
authors.forename: K
authors.initials: K
authors.lastname: Weismüller
authors.forename: J
authors.initials: J
authors.lastname: Engel
authors.forename: I D
authors.initials: ID
authors.lastname: Welters
authors.forename: T W
authors.initials: TW
authors.lastname: Langefeld
authors.forename: M
authors.initials: M
authors.lastname: Fuchs
authors.forename: M A
authors.initials: MA
authors.lastname: Weigand
authors.forename: M C
authors.initials: MC
authors.lastname: Heidt
mesh_terms: D000328:Adult; D000596:Amino Acids / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D007651:Keto Acids / Q000378:metabolism*; D007656:Ketoglutaric Acids / Q000494:pharmacology*; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000596:Amino Acids; D007651:Keto Acids; D007656:Ketoglutaric Acids; D017382:Reactive Oxygen Species