Urinary citrate is a key inhibitor of nephrolithiasis, and thus its concentration in the urine is of great importance. The amount of citrate in the urine is determined primarily by the rate of proximal tubular citrate absorption. In this nephron segment, citrate is reabsorbed across the luminal membrane, and is then metabolized. In previous studies, we and others have identified two potential pathways of proximal tubule citrate metabolism: 1) a cytoplasmic pathway involving metabolism by ATP citrate lyase; and 2) a mitochondrial pathway involving metabolism in the citric acid cycle. Both of these pathways are up-regulated in hypocitraturic conditions. However, it is not presently known which of these pathways is quantitatively more important. 13C NMR provides an excellent method to examine the pathway of citrate metabolism in the renal cortex (which is comprised mostly of proximal tubule). The purpose of these studies was to examine whether this approach is feasible, and to determine if blood citrate is oxidized in the kidney in vivo. Rats were infused with [2,3,4-13C] citrate and at the end of the infusion period, a laparatomy was performed and the kidneys and liver freeze-clamped and extracted. The 13C NMR data demonstrate that following infusion of [2,3,4-13C] citrate, spin-spin coupling was observed in the C2, C3, and C4 signals of renal glutamate. This spin-spin coupling proves that the renal signal is derived from the infused [2,3,4-13C] citrate. No spin-spin coupling in the glutamate resonances were found in the liver spectrum indicating little if any hepatic metabolism of the infused tracer citrate. This is consistent with the dogma in the field that the liver does not take up citrate from the extracellular fluid. These results demonstrate that extracellular citrate is oxidized by the kidney in vivo, but oxidation of citrate by the liver could not be detected in the same animals. (Collaborative 6) REPORT PERIOD: (09/01/97-08/31/98)
|Effective start/end date||10/1/95 → 9/30/99|
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