Effect of fluorocitrate on cerebral oxidation of lactate and glucose in freely moving rats.
Glucose is the primary carbon source to enter the adult brain for catabolic and anabolic reactions. Some studies suggest that astrocytes may metabolize glucose to lactate; the latter serving as a preferential substrate for neurons, especially during neuronal activation. The current study utilizes the aconitase inhibitor fluorocitrate to differentially inhibit oxidative metabolism in glial cells in vivo. Oxidative metabolism of 14C-lactate and 14C-glucose was monitored in vivo using microdialysis and quantitating 14CO2 in the microdialysis eluate following pulse labeling of the interstitial glucose or lactate pool. After establishing a baseline oxidation rate, fluorocitrate was added to the perfusate. Neither lactate nor glucose oxidation was affected by 5 micromol/L fluorocitrate. However, 20 and 100 micromol/L fluorocitrate reduced lactate oxidation by 55 +/- 20% and 68 +/- 12%, respectively (p < 0.05 for both). Twenty and 100 micromol/L fluorocitrate reduced 14C-glucose oxidation by 50 +/- 14% (p < 0.05) and 24 +/- 19% (ns), respectively. Addition of non-radioactive lactate to (14)C-glucose plus fluorocitrate decreased 14C-glucose oxidation by an additional 29% and 38%, respectively. These results indicate that astrocytes oxidize about 50% of the interstitial lactate and about 35% of the glucose. By subtraction, neurons metabolize a maximum of 50% of the interstitial lactate and 65% of the interstitial glucose.
Zielke
H Ronald
HR
Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland 21010, USA. rzielke@umaryland.edu
Zielke
Carol L
CL
Baab
Peter J
PJ
Tildon
J Tyson
JT
D000154:Aconitate Hydratase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D002250:Carbon Radioisotopes; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism*; D002951:Citrates / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D007773:Lactates / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D009068:Movement / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D002250:Carbon Radioisotopes; D002951:Citrates; D004791:Enzyme Inhibitors; D007773:Lactates; C007744:fluorocitrate; D000154:Aconitate Hydratase; D005947:Glucose