PD04-05 TARGETING HYDROXYPROLINE DEHYDROGENASE AS A POTENTIAL THERAPY FOR TYPE 2 PRIMARY HYPEROXALURIA

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Hydroxyproline metabolism in mouse models of primary hyperoxaluria

John Knight, Ross P. Holmes, Scott D. Cramer, Tatsuya Takayama, and Eduardo Salido Departments of Urology and Cancer Biology, Wake Forest University Health Sciences, Winston-Salem, North Carolina; Department of Pharmacology, University of Colorado, Denver, Anschutz Medical Campus, Aurora, Colorado; and Center for Biomedical Research on Rare Diseases, Hospital Universitario Canarias, Instituto T...

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Re: hydroxyproline metabolism in mouse models of primary hyperoxaluria.

Primary hyperoxaluria type 1 (PH1) and type 2 (PH2) are rare genetic diseases that result from deficiencies in glyoxylate metabolism. The increased oxalate synthesis that occurs can lead to kidney stone formation, deposition of calcium oxalate in the kidney and other tissues, and renal failure. Hydroxyproline (Hyp) catabolism, which occurs mainly in the liver and kidney, is a prominent source o...

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High throughput cell-based assay for identification of glycolate oxidase inhibitors as a potential treatment for Primary Hyperoxaluria Type 1

Glycolate oxidase (GO) and alanine:glyoxylate aminotransferase (AGT) are both involved in the peroxisomal glyoxylate pathway. Deficiency in AGT function causes the accumulation of intracellular oxalate and the primary hyperoxaluria type 1 (PH1). AGT enhancers or GO inhibitors may restore the abnormal peroxisomal glyoxylate pathway in PH1 patients. With stably transformed cells which mimic the g...

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Molecular Requirements for Peroxisomal Targeting of Alanine-Glyoxylate Aminotransferase as an Essential Determinant in Primary Hyperoxaluria Type 1

Alanine-glyoxylate aminotransferase is a peroxisomal enzyme, of which various missense mutations lead to irreversible kidney damage via primary hyperoxaluria type 1, in part caused by improper peroxisomal targeting. To unravel the molecular mechanism of its recognition by the peroxisomal receptor Pex5p, we have determined the crystal structure of the respective cargo-receptor complex. It shows ...

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Bilateral nephrocalcinosis in primary hyperoxaluria type 1

A 31-year-old male presented with recurrent renal stones from the age of 12 years and renal failure secondary to nephrolithiasis on hemodialysis for the past 6 years. He had been born of a consanguineous union and one out of his five siblings also had a history of renal failure secondary to nephrolithiasis. He had moderate anemia. Abdominal X-ray showed bilateral nephrocalcinosis with multiple ...

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ژورنال

عنوان ژورنال: Journal of Urology

سال: 2020

ISSN: 0022-5347,1527-3792

DOI: 10.1097/ju.0000000000000824.05