title: Glutaminase catalyzes reaction of glutamate to GABA.
abstract: Here, for the first time, we report an NMR spectroscopy study of l-Glutamine (Gln) conversion by Glutaminase (Glnase), which shows that the reaction involves two distinct steps. In the first step, Glnase rapidly hydrolyzes Gln to Glutamate (Glu) (∼16.87 μmol of Gln/min/mg of Glnase) and in the second step, Glu generated in the first step is decarboxylated into gamma-amino butyric acid (GABA) with a much slower rate (∼0.185 μmol/min/mg). When Glnase was added to the sample containing l-Glu alone, it was also converted to GABA, at a similar rate as in the second step mentioned above. The rate of Glu decarboxylation into GABA by Glnase is about an order of magnitude lower than that by commonly known enzyme, Glutamate decarboxylase. Potential impact of these findings, on the mechanistic aspects of Gln-Glu shuttle in neuroscience and glutaminolysis in tumors, is discussed.
authors.affiliation: Center for Magnetic Resonance and Optical Imaging, Department of Radiology, University of Pennsylvania, B1 Stellar-Chance Laboratories, 422 Curie Boulevard, Philadelphia, PA 19104, USA.
authors.forename: Ravi Prakash Reddy
authors.initials: RP
authors.lastname: Nanga
authors.affiliation: Center for Magnetic Resonance and Optical Imaging, Department of Radiology, University of Pennsylvania, B1 Stellar-Chance Laboratories, 422 Curie Boulevard, Philadelphia, PA 19104, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: DeBrosse
authors.affiliation: Center for Magnetic Resonance and Optical Imaging, Department of Radiology, University of Pennsylvania, B1 Stellar-Chance Laboratories, 422 Curie Boulevard, Philadelphia, PA 19104, USA.
authors.forename: Anup
authors.initials: A
authors.lastname: Singh
authors.affiliation: Center for Magnetic Resonance and Optical Imaging, Department of Radiology, University of Pennsylvania, B1 Stellar-Chance Laboratories, 422 Curie Boulevard, Philadelphia, PA 19104, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: D'Aquilla
authors.affiliation: Center for Magnetic Resonance and Optical Imaging, Department of Radiology, University of Pennsylvania, B1 Stellar-Chance Laboratories, 422 Curie Boulevard, Philadelphia, PA 19104, USA.
authors.forename: Hari
authors.initials: H
authors.lastname: Hariharan
authors.affiliation: Center for Magnetic Resonance and Optical Imaging, Department of Radiology, University of Pennsylvania, B1 Stellar-Chance Laboratories, 422 Curie Boulevard, Philadelphia, PA 19104, USA. Electronic address: krr@mail.med.upenn.edu.
authors.forename: Ravinder
authors.initials: R
authors.lastname: Reddy
mesh_terms: D001921:Brain / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D005972:Glutaminase / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D005972:Glutaminase; D005968:Glutamate Decarboxylase; D005947:Glucose
keywords: GABA; Glutamate; Glutamic acid decarboxylase; Glutaminase; Glutamine; Glutaminolysis
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