title: The ratio of acetate-to-glucose oxidation in astrocytes from a single 13C NMR spectrum of cerebral cortex.
abstract: The (13) C-labeling patterns in glutamate and glutamine from brain tissue are quite different after infusion of a mixture of (13) C-enriched glucose and acetate. Two processes contribute to this observation, oxidation of acetate by astrocytes but not neurons, and preferential incorporation of α-ketoglutarate into glutamate in neurons, and incorporation of α-ketoglutarate into glutamine in astrocytes. The acetate:glucose ratio, introduced previously for analysis of a single (13) C NMR spectrum, provides a useful index of acetate and glucose oxidation in the brain tissue. However, quantitation of relative substrate oxidation at the cell compartment level has not been reported. A simple mathematical method is presented to quantify the ratio of acetate-to-glucose oxidation in astrocytes, based on the standard assumption that neurons do not oxidize acetate. Mice were infused with [1,2-(13) C]acetate and [1,6-(13) C]glucose, and proton decoupled (13) C NMR spectra of cortex extracts were acquired. A fit of those spectra to the model indicated that (13) C-labeled acetate and glucose contributed approximately equally to acetyl-CoA (0.96) in astrocytes. As this method relies on a single (13) C NMR spectrum, it can be readily applied to multiple physiologic and pathologic conditions. Differences in (13) C labeling of brain glutamate and glutamine have been attributed to metabolic compartmentation. The acetate:glucose ratio, introduced for description of a (13) C NMR (nuclear magnetic resonance) spectrum, is an index of glucose and acetate oxidation in brain tissue. A simple mathematical method is presented to quantify the ratio of acetate-to-glucose oxidation in astrocytes from a single NMR spectrum. As kinetic analysis is not required, the method is readily applicable to analysis of tissue extracts. α-KG = alpha-ketoglutarate; CAC = citric acid cycle; GLN = glutamine; GLU = glutamate.
authors.affiliation: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA; Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA.
authors.forename: Isaac
authors.initials: I
authors.lastname: Marin-Valencia
authors.forename: M Ali
authors.initials: MA
authors.lastname: Hooshyar
authors.forename: Kumar
authors.initials: K
authors.lastname: Pichumani
authors.forename: A Dean
authors.initials: AD
authors.lastname: Sherry
authors.forename: Craig R
authors.initials: CR
authors.lastname: Malloy
mesh_terms: D000085:Acetates / Q000378:metabolism*; D000105:Acetyl Coenzyme A / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000737:chemistry / Q000378:metabolism*; D002540:Cerebral Cortex / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D007656:Ketoglutaric Acids / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000737:chemistry / Q000378:metabolism; D010084:Oxidation-Reduction
chemical_list: D000085:Acetates; D007656:Ketoglutaric Acids; D005973:Glutamine; D018698:Glutamic Acid; D000105:Acetyl Coenzyme A; D005947:Glucose
keywords: acetate; glia; glucose; neuron