Exchange-mediated dilution of brain lactate specific activity: implications for the origin of glutamate dilution and the contributions of glutamine dilution and other pathways.
The magnitude of metabolic activation is greatly underestimated in autoradiographic studies using [1- or 6-14C]glucose compared to parallel assays with [14C]deoxyglucose indicating that most of the label corresponding to the additional [14C]glucose consumed during activation compared to rest is quickly released from activated structures. Label could be lost by net release of [14C]lactate from brain or via lactate exchange between blood and brain. These possibilities were distinguished by comparison of glucose and lactate specific activities in arterial blood and brain before, during, and after generalized sensory stimulation and during spreading cortical depression. Over a wide range of brain lactate concentrations, lactate specific activity was close to the theoretical maximum, i.e. half that of [6-14C]glucose, indicating that exchange-mediated dilution of lactate is negligible and that efflux of [14C]lactate probably accounts for most of the label loss. Low lactate dilution also indicates that dilution of glutamate C4 fractional enrichment in [13C]glucose studies, currently ascribed predominantly to lactate exchange, arises from other unidentified pathways or factors. Alternative explanations for glutamate dilution (presented in Supporting Information) include poorly labeled amino acid pools and oxidative metabolism of minor substrates in astrocytes to first dilute the astrocytic glutamine pool, followed by dilution of glutamate via glutamate-glutamine cycling.
Dienel
Gerald A
GA
Department of Neurology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA. gadienel@uams.edu
Cruz
Nancy F
NF
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001345:Autoradiography; D001786:Blood Glucose / Q000378:metabolism; D001923:Brain Chemistry / Q000502:physiology*; D013181:Cortical Spreading Depression / Q000502:physiology; D018698:Glutamic Acid / Q000097:blood / Q000378:metabolism*; D005973:Glutamine / Q000097:blood / Q000378:metabolism*; D019344:Lactic Acid / Q000097:blood / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D012677:Sensation / Q000502:physiology
D000596:Amino Acids; D001786:Blood Glucose; D005973:Glutamine; D019344:Lactic Acid; D018698:Glutamic Acid