Kidney phenylalanine hydroxylase from man and rat. Comparison with the liver enzyme

Ayling, June E.; Pirson, Wolfgang; Al-Janabi, Jasim M.; Helfand, G D

doi:10.1021/bi00698a013

Cited by 43 publications

(18 citation statements)

References 16 publications

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“…Comparative studies which we have made with rat liver and kidney phenyl alanine hydroxylases showed that the immunological reactivity of rat kidney enzyme was identical to that of the rat liver enzyme with rat liver enzyme antibodies [3]. By analogy, the human kidney enzyme should produce anti bodies which will cross react with human liver enzyme and which could thus be used for isolation of mutant human hepatic phenylalanine hydroxylases.…”

Section: Discussionmentioning

confidence: 80%

Phenylalanine Hydroxylase from Human Kidney

Je¹,

Gd²,

Wd³

1975

Enzyme

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In this report the presence, and level, of phenylalanine hydroxylase in the cortex of human kidney is established. The average activity found in 15 surgically removed kidneys was 47.2 ± 11.2 mU/g wet weight of tissue. The average value, determined under the same experimental conditions, for two human liver biopsies was 217 mU/g tissue. Of five autopsy livers obtained 2.5-4 h postmortem, four contained no activity, and only 1-2% of normal was found in the fifth. Autopsy kidneys were similarly inactive. The presence of a highly active degradative enzyme could not be demonstrated in autopsy liver homogenates; it was established that the lack of activity was not due to an inhibitory component. A possible interpretation of this phenomenon is discussed. According to work published elsewhere [3] the kidney and liver enzymes appear to be similar. Thus, surgically removed kidneys provide an alternative source of human phenylalanine hydroxylase which can be used to study phenylketonuria.

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Section: Discussionmentioning

confidence: 80%

Phenylalanine Hydroxylase from Human Kidney

Je¹,

Gd²,

Wd³

1975

Enzyme

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“…It is, therefore, likely that the inability to demonstrate the enzyme activity in autopsy samples (9) is related to the instability of this enzyme. Further studies have demonstrated that the same isoenzymes of phenylalanine hydroxylase exist in the liver and kidney (25). The kidney also has been reported to release Tyr on long-term fasting (26) and in subjects renal catheterization is done for diagnostic purpose (19).…”

Section: Discussionmentioning

confidence: 99%

“…It has also been reported that the enzyme in kidney is less stable than that in liver (24). However, the stability has been shown to be the same after purification, indicating that the kidney enzyme is unstable in kidney extract (25). It is, therefore, likely that the inability to demonstrate the enzyme activity in autopsy samples (9) is related to the instability of this enzyme.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, phenylalanine hydroxylase has also been demonstrated in the human kidney cortex (23), although studies based on biopsy samples from diseased kidney and autopsy samples failed to demonstrate phenylalanine hydroxylase in human kidney (9,24). It should be emphasized that needle biopsy samples from diseased kidney may not represent the whole kidney, and careful studies based on freshly removed kidney demonstrated this enzyme activity in the human kidney (25). It has also been reported that the enzyme in kidney is less stable than that in liver (24).…”

Section: Discussionmentioning

confidence: 99%

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

Møller

Meek

Bigelow

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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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.

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“…Differences in incubation time in the enzyme assay may also contribute to the kinetic differences. PAH is expressed in human kidney in vivo (Ayling et al, 1974), and the A293 embryonic kidney cells (with no detectable basal expression of PAH) are therefore probably the most representative in vitro system relating to the in vivo situation. However, large amounts of purified protein is required for detailed biochemical characterization of normal and mutant PAH proteins and this is only obtained from overexpression in E. coli.…”

Section: Produced In Three Different Expression Systemsmentioning

confidence: 99%