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Metabolism and excretion of carnitine and acylcarnitines in the perfused rat kidney
Institution:1. ZIEL Institute for Food and Health, Technical University of Munich, Freising, Germany;2. Research Unit Analytical BioGeoChemistry, Helmholtz Zentrum München, Neuherberg, Germany;3. Chair of Analytical Food Chemistry, Technical University of Munich, Freising, Germany;1. Chair of Analytical Food Chemistry, Technical University of Munich (TUM), Freising, Germany;2. Helmholtz Zentrum München, Research Unit, Analytical BioGeoChemistry, Neuherberg, Germany
Abstract:Rat kidneys were perfused for 30 min with a Krebs-Henseleit bicarbonate buffer with 5 mM glucose. Albumin proved superior to pluronic polyols as oncotic agent with regard to carnitine reabsorption in the perfused kidney. The reabsorption of 30 μM (−)-methyl-3H]carnitine was approx. 96% during the first 10 min. At 750 μM the reabsorption decreased to 40%. The tubular reabsorptive maximum (Tmax) was approx. 170 nmol/min per kidney. The fractional reabsorption and clearance of (+)-carnitine, γ-butyrobetaine, and carnitine esters did not deviate significantly from that of (−)-carnitine. (+)-Carnitine was not metabolized by the perfused kidney. In perfusions with (−)-carnitine or (−)-carnitine plus 10 mM α-ketoisocaproate or α-ketoisovalerate increased amounts of acetylcarnitine, isovalerylcarnitine and isobutyrylcarnitine were found. Propionate (5 mM) inhibited acetylcarnitine formation. Isovalerylcarnitine, isobutyrylcarnitine and propionylcarnitine were actively degraded to free (−)-carnitine. In urine, we found a disproportionally high excretion of carnitine or carnitine esters formed in the kidney, compared to the same derivatives when ultrafiltrated. Leakage of metabolites formed in the kidney into preurine may explain this phenomenon.
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