The effects of fluorocitrate on renal glutamine, lactate, alanine, and oxygen metabolism in the dog.
Acid-base status is considered the major factor controlling renal NH4+ production from glutamine, with maximal values found in chronic acidosis. However, metabolic inhibitors have been shown to increase NH4+ production without acid-base change; the mechanism for this increase is unclear. Fluorocitrate was administered to dogs with chronic metabolic alkalosis. Following fluorocitrate total renal NH4+ production rose from 32 +/- 5 to 104 +/- 15 mumol/(min.100 mL glomerular filtration rate (GFR] (p less than 0.01) and glutamine extraction rose from 26 +/- 8 to 65 +/- 8 mumol/(min.100 mL GFR) (p less than 0.01). These values approximate maximal values found in chronic acidosis. Lactate utilization fell from 165 +/- 19 to 99 +/- 7 mumol/(min.100 mL GFR) following fluorocitrate (p less than 0.01). Citrate extraction fell to zero and alanine production rose from 27 +/- 4 to 46 +/- 7 mumol/(min.100 mL GFR) (p less than 0.01). Oxygen consumption remained unchanged following fluorocitrate, 584 +/- 29 vs. 549 +/- 29 mumol/(min.100 mL GFR). These results demonstrate that in the presence of metabolic inhibition in the kidney, ATP production remains constant. This is achieved by increased utilization of one substrate, glutamine, when the ATP production from other substrates is reduced. Thus the necessity to maintain constant ATP production appears to modulate renal NH4+ production.
Department of Medicine, St. Boniface General Hospital, Winnipeg, Man., Canada.
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Fine
D000255:Adenosine Triphosphate / Q000378:metabolism; D000409:Alanine / Q000378:metabolism*; D000818:Animals; D002951:Citrates / Q000494:pharmacology*; D004285:Dogs; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005973:Glutamine / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D007773:Lactates / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*
D002951:Citrates; D007773:Lactates; D005973:Glutamine; C007744:fluorocitrate; D000255:Adenosine Triphosphate; D000409:Alanine