The kidney is an important site for in vivo phenylalanine-to-tyrosine conversion in adult humans: A metabolic role of the kidney

Abstract

Synthesis of Tyr in the human body occurs by hydroxylation of the indispensable amino acid Phe. Until now, it was believed that in humans, this process was restricted to the liver, but we provide compelling evidence of production of Tyr from Phe in the kidney. To determine whether the human kidney produces Tyr, we measured Tyr balance, the Tyr appearance rate, and the Phe-to-Tyr conversion in 12 healthy human subjects by using [ 15 N]Phe and [ 2 H4]Tyr as tracers. Renal plasma flow was measured by using paraaminohippurate, and sampling from the femoral artery and renal veins was performed. The results were compared with those obtained in 12 control subjects undergoing hepatic vein catheterization and infusion of identical tracers. In all 12 subjects, there was a net uptake of Phe by the kidney (2.2 ؎ 1.2 mol͞min), whereas Tyr was released (5.3 ؎ 1.5 mol͞min). In contrast, there was a net uptake of both Phe (9.5 ؎ 1.2 mol͞min) and Tyr (14.3 ؎ 1.3 mol͞min) by the splanchnic bed. Phe conversion to Tyr occurred at a rate of 5.2 ؎ 1.2 mol͞min in kidney and 3.0 ؎ 0.7 mol͞min in the splanchnic bed. The kidney contributed a substantial amount of Tyr to the systemic circulation where the splanchnic bed was a net remover of Tyr. Our results demonstrate that the kidney is the major donor of Tyr to the systemic circulation by its conversion of Phe to Tyr. This observation may have important clinical implications for patients with both renal and hepatic disease, who may be at risk of Phe overloading and Tyr deficiency, and it should be considered when parenteral or enteral nutrients are administered rich in Phe and low in Tyr.

Renal amino acid, fat and glucose metabolism in type 1 diabetic and non-diabetic humans: effects of acute insulin withdrawal

“…The discrepancy could relate to the different patient categories studied, because it cannot be excluded that patients with hypertension and cardiac disease may have subtly compromised renal function. Finally, we confirm our recent observation that the kidney is an important site for phenylalanine-to-tyrosine conversion [14], by showing that this also applies to diabetic subjects, in whom we observed renal conversion rates of around 5 μmol/min, regardless of whether insulin was administered. This indicates that the kidney's key role as a supplier of tyrosine to the systemic circulation during the postabsorptive state is unaffected by insulin deficiency and the associated metabolic derangements.…”

“…Plasma enrichment levels of 15 N]leucine and [1-13 C] leucine were determined by gas chromatography/mass spectrometry as described elsewhere [3,14].…”

“…A recent report used renal vein catheterisation and radioactive amino acid tracers and demonstrated that in non-diabetic postabsorptive humans 25% of leucine oxidation and around 10% of leucine appearance and leucine protein synthesis took place in the kidney [13]. The kidney has also been shown to be a major site of phenylalanine conversion to tyrosine and a contributor of tyrosine to the circulation [14].…”

Kidney Protein Dynamics and Ammoniagenesis in Humans with Chronic Metabolic Acidosis

“…Although the reduced release of glutamate is consistent with its use as an ammoniagenic source, the decrease in kidney amino acid output (such as tyrosine and serine) is in agreement with the decrease in intrarenal protein breakdown that is observed in acidemic subjects. Tyrosine, a semiessential amino acid whose renal production is blunted in acidosis, partly derives from phenylalanine hydroxylation and partly from intrarenal protein breakdown (34,35). Serine is likely produced from glycine by the intrarenal breakdown of cysteinyl-glycine, which is released by glutathione hydrolysis from peripheral and splanchnic tissues and filtered by glomeruli (36).…”

Performance of piglets in response to the standardized ileal digestible phenylalanine and tyrosine supply in low-protein diets

“…In contrast to our results, Sasse and Baker (1972) determined that Phe was equal in efficacy to Tyr, on a molar basis, to provide Tyr in young chicks. In adult humans, Møller et al (2000) demonstrated that in the postabsorptive state, the kidney is a net contributor of Tyr to the systemic circulation while the liver removes Tyr from the circulation. It can be expected that the majority of Tyr synthesized in the liver from Phe hydroxylation is degraded as soon as it is synthesized and not available for whole body protein synthesis.…”