N-carbamylglutamate markedly enhances ureagenesis in N-acetylglutamate deficiency and propionic acidemia as measured by isotopic incorporation and blood biomarkers.

Pediatric Research
M TuchmanM Yudkoff

Abstract

N-acetylglutamate (NAG) is an endogenous essential cofactor for conversion of ammonia to urea in the liver. Deficiency of NAG causes hyperammonemia and occurs because of inherited deficiency of its producing enzyme, NAG synthase (NAGS), or interference with its function by short fatty acid derivatives. N-carbamylglutamate (NCG) can ameliorate hyperammonemia from NAGS deficiency and propionic and methylmalonic acidemia. We developed a stable isotope (13)C tracer method to measure ureagenesis and to evaluate the effect of NCG in humans. Seventeen healthy adults were investigated for the incorporation of (13)C label into urea. [(13)C]urea appeared in the blood within minutes, reaching maximum by 100 min, whereas breath (13)CO(2) reached a maximum by 60 min. A patient with NAGS deficiency showed very little urea labeling before treatment with NCG and normal labeling thereafter. Correspondingly, plasma levels of ammonia and glutamine decreased markedly and urea tripled after NCG treatment. Similarly, in a patient with propionic acidemia, NCG treatment resulted in a marked increase in urea labeling and decrease in glutamine, alanine, and glycine. These results provide a reliable method for measuring the effect of NCG on nitrogen meta...Continue Reading

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Citations

May 31, 2012·Orphanet Journal of Rare Diseases·Johannes HäberleCarlo Dionisi-Vici
Mar 16, 2011·International Journal of General Medicine·Marta DaniottiLuca Filippi
Jun 10, 2014·Nature Biotechnology·Philip J BrooksSteve Groft
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Aug 8, 2009·Molecular Genetics and Metabolism·Nicholas Ah MewMarc Yudkoff
Dec 17, 2015·Omics : a Journal of Integrative Biology·Sunil KoundalSubash Khushu
Jul 19, 2015·Regulatory Toxicology and Pharmacology : RTP·Xin WuYulong Yin
Jun 23, 2015·The Journal of Clinical Investigation·Ting-Chin David ShenGary D Wu
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Dec 10, 2020·Anais Da Academia Brasileira De Ciências·Diogo DominguiniFelipe Dal-Pizzol
Mar 6, 2018·Pediatric Clinics of North America·Marshall L Summar, Nicholas Ah Mew

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