전한울
2018년 12월 19일
- Summary of Brain Glucose Metabolism:
Glucose is the primary energy source for the brain, fulfilling critical functions including ATP production, oxidative stress management, and synthesis of neurotransmitters. Neuronal glucose oxidation exceeds that in astrocytes, but both increase proportionally with excitatory neurotransmission. The glutamate-glutamine cycle between neurons and astrocytes is tightly coupled to glucose metabolism. Aerobic glycolysis occurs during brain activation even when oxygen is sufficient. Three major pathways contribute to glucose utilization in excess of oxygen: glycolysis, the pentose phosphate shunt, and glycogen turnover. Adrenergic regulation influences aerobic glycolysis. Nutritional therapy and vagus nerve stimulation provide translational approaches from metabolism to clinical treatment of brain disorders.
<논문요약>
I. Introduction
A. Glucose: The Brain's Obligatory Fuel
Earliest studies in 1920s-1930s showed carbohydrate as major fuel
Respiratory quotient (RQ) of 1.00 indicates carbohydrate metabolism
Glucose established as major energy source for brain
Most glucose oxidized to CO2 + H2O, some converted to lactate
B. Minor Oxidative Substrates
Short-chain monocarboxylic acids, octanoate, decanoate
Fatty acids readily oxidized by astrocytes
Amino acids can be oxidized but contribute less than glucose
C. Glucose-Derived ATP and Carbon
Brain relies on glucose catabolism for ATP generation
Glucose is precursor for many compounds synthesized in brain
~70% of energy demands associated with neuronal signaling
~30% for nonsignaling activities
D. Assay Methods
Radioactive and stable isotopes used to track metabolism
Development of [14C]DG and [18F]FDG methods for imaging
Magnetic resonance spectroscopy (MRS) for metabolic studies
E. Metabolic Rates
Whole-brain CMRglc in humans ~0.2-0.3 μmol/g/min
Brain consumes ~91g glucose/day
Whole-brain CMRO2 ~3.3-4.2 ml/100g/min or 1.5-1.9 μmol/g/min
F. High Oxidative Rate
Brain recognized as highly oxidative organ
Can increase CMRO2 by 2-3 fold for at least 2 hours
Higher metabolic rate during development
G. Consequences of Insufficient Glucose or Oxygen
Hypoglycemia or hypoxia can degrade brain function
Severity depends on magnitude and duration of deficit
Even with acclimatization, cognitive deficits can occur at high altitudes
H. Perspective
Glucose fulfills many essential functions in brain
Quantitative assays of glucose utilization and pathway fluxes
Complexities of glucose involvement in neurotransmission
Controversial topics: astrocyte-neuron lactate shuttling, aerobic glycolysis, glycogen roles
II. Glucose Metabolism and Metabolic Assays
A. Major Pathways of Glucose Metabolism in Brain
1. Glucose delivery to brain
Transported via GLUT transporters
Brain-to-plasma distribution ratio ~0.2
Maximal transport capacity 2-3 fold greater than resting utilization
2. ATP generation from glucose catabolism
Glycolysis produces 2 ATP
Oxidation produces ~30 ATP
Total yield ~32 ATP per glucose molecule oxidized
doi:10.1152/physrev.00062.2017
Glucose is the long-established, obligatory fuel for brain that fulfills many critical functions, including ATP production, oxidative stress management, and synthesis of neurotransmitters, neuromodulators, and structural components. Neuronal glucose oxidation exceeds that in astrocytes, but both rates increase in direct proportion to excitatory neurotransmission; signaling and metabolism are closely coupled at the local level. Exact details of neuron–astrocyte glutamate– glutamine cycling remain to be established, and the specific roles of glucose and lactate in the cellular energetics of these processes are debated. Glycolysis is preferentially upregulated during brain activation even though oxygen availability is sufficient (aerobic glycolysis). Three major pathways, glycolysis, pentose phosphate shunt, and glycogen turnover, contribute to utilization of glucose in excess of oxygen, and adrenergic regulation of aerobic glycolysis draws attention to astrocytic metabolism, particularly glycogen turnover, which has a high impact on the oxygen– carbohydrate mismatch. Aerobic glycolysis is proposed to be predominant in young children and specific brain regions, but re-evaluation of data is necessary. Shuttling of glucose- and glycogen-derived lactate from astrocytes to neurons during activation, neurotransmission, and memory consolidation are controversial topics for which alternative mechanisms are proposed. Nutritional therapy and vagus nerve stimulation are translational bridges from metabolism to clinical treatment of diverse brain disorders