In vivo measurement of ureagenesis with stable isotopes.
We have utilized stable isotopes to measure in vivo rates of ureagenesis. In one testing procedure, 15NH4Cl was administered orally to controls and to heterozygotes for ornithine transcarbamylase deficiency. Controls produced [15N]urea at a rate that was greater than that of symptomatic carriers, but indistinguishable from that of asymptomatic carriers. In contrast, both symptomatic and asymptomatic heterozygotes produced [5-15N]glutamine more rapidly than the controls. Ureagenesis could also be measured by administering sodium [1-13C]acetate to a healthy adult and measuring subsequent formation of [13C]urea. The latter approach involves the use of isotope ratio mass spectrometry to determine isotopic abundance. This technique is much more sensitive than gas chromatography-mass spectrometry for the measurement of isotopic label, a consideration that makes the method more suitable for the study of subjects in whom ureagenesis is severely compromised, for example the human male neonate with a near complete deficiency of ornithine transcarbamylase.
Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, USA.
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M
Yudkoff
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Daikhin
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Ye
J M
JM
Wilson
M L
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Batshaw
D000328:Adult; D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis / Q000378:metabolism* / Q000628:therapy; D000643:Ammonium Chloride / Q000378:metabolism; D001944:Breath Tests; D002245:Carbon Dioxide / Q000097:blood / Q000378:metabolism; D002247:Carbon Isotopes; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006580:Genetic Carrier Screening; D005973:Glutamine / Q000096:biosynthesis; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D009587:Nitrogen Isotopes; D020163:Ornithine Carbamoyltransferase Deficiency Disease; D019346:Sodium Acetate / Q000378:metabolism; D014508:Urea / Q000097:blood / Q000378:metabolism*
D002247:Carbon Isotopes; D009587:Nitrogen Isotopes; D000643:Ammonium Chloride; D005973:Glutamine; D002245:Carbon Dioxide; D019346:Sodium Acetate; D014508:Urea