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5-Methyltetrahydrofolate Is Reabsorbed and Metabolized in Isolated Perfused Rat Kidney¹

Department of Pharmacology, Louisiana State University Medical Center, Shreveport, LA 71130-3932

The renal regulation of folate excretion is an important component in maintaining the body burden of folate. The tubular processes for folate disposition have been examined by a variety of methods to elucidate the mechanism by which renal folate excretion is regulated. Accordingly, the isolated perfused rat kidney technique was evaluated by investigating the clearance and metabolic patterns of 5-methyltetrahydrofolate (5-CH₃-H₄PteGlu). Kidneys from male Sprague-Dawley rats were perfused in vitro with [³H]5-CH₃-H₄PteGlu (1–2000 nmol/L). Linear regression analysis of 5-CH₃-H₄PteGlu excretion vs. filtered load revealed a tubular transport maximum of 7.5 pmol·min^-1·g^-1. A dual component system for tubular transport of 5-CH₃-H₄PteGlu was found: a high capacity, nonsaturable system and a low capacity, saturable system represented by the transport maximum. Furthermore, HPLC analysis of urine demonstrated renal uptake and metabolism of the labeled tracer. Tetrahydrofolate was identified as one metabolic product that indicated secretion of this compound. Additional metabolites were identified from kidney samples. Results suggest that 5-CH₃-H₄PteGlu undergoes net reabsorption by a dual component transport system; some of the reabsorbed 5-CH₃-H₄PteGlu is metabolized to other products that may be secreted in the urine.

KEY WORDS: • folate • renal clearance • 5-methyltetrahydrofolate • rats • perfused kidney

¹ Supported by U.S. Public Health Service grant RO1-AA05308.

Manuscript received 7 February 1992. Revision accepted 25 August 1992.

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