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Article: Pyruvate ameliorates the defect in ureogenesis from ammonia in citrin-deficient mice

TitlePyruvate ameliorates the defect in ureogenesis from ammonia in citrin-deficient mice
Authors
KeywordsAdult-onset type II citrullinemia
Argininosuccinate synthetase
Citrin deficiency
Hyperammonemia
Pyruvate
Redox state
Ureogenesis
Issue Date2006
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/jhep
Citation
Journal Of Hepatology, 2006, v. 44 n. 5, p. 930-938 How to Cite?
AbstractBackground/Aims: Mutations in SLC25A13, encoding the mitochondrial aspartate-glutamate carrier citrin, cause adult-onset type II citrullinemia (CTLN2) in humans. We have previously reported that although citrin-knockout (Ctrn-/-) mice fail to display symptoms of CTLN2, liver perfusion revealed a deficit in ureogenesis from ammonia accompanied by an increase in the perfusate lactate-to-pyruvate (L/P) ratio. The present study explores the effects of pyruvate, aspartate and citrate on improving the abnormalities observed in the Ctrn-/- liver. Methods: We measured the rate of ureogenesis from ammonium chloride using the liver-perfusion system. Results: Pyruvate infusion lowered the L/P ratio and corrected the deficit in ureogenesis in the Ctrn-/- liver. This effect was found to be dose-dependent in both instances. Phenazine methosulfate, a cytosolic oxidant, also improved the rate of ureogenesis in the Ctrn-/- liver and led to a fall in the L/P ratio. The addition of aspartate or citrate did not change either the rate of ureogenesis or the L/P ratio in the Ctrn-/- liver. Conclusions: Citrin deficiency disturbs urea synthesis primarily as a result of an elevated cytosolic NADH/NAD+ ratio owing to limited reoxidation of reducing equivalents. Clinically, pyruvate may have a therapeutic benefit for CTLN2 patients. © 2005 European Association for the Study of the Liver.
Persistent Identifierhttp://hdl.handle.net/10722/143607
ISSN
2014 Impact Factor: 11.336
2014 SCImago Journal Rankings: 3.477
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorMoriyama, Men_HK
dc.contributor.authorLi, MXen_HK
dc.contributor.authorKobayashi, Ken_HK
dc.contributor.authorSinasac, DSen_HK
dc.contributor.authorKannan, Yen_HK
dc.contributor.authorIijima, Men_HK
dc.contributor.authorHoriuchi, Men_HK
dc.contributor.authorTsui, LCen_HK
dc.contributor.authorTanaka, Men_HK
dc.contributor.authorNakamura, Yen_HK
dc.contributor.authorSaheki, Ten_HK
dc.date.accessioned2011-12-15T03:39:30Z-
dc.date.available2011-12-15T03:39:30Z-
dc.date.issued2006en_HK
dc.identifier.citationJournal Of Hepatology, 2006, v. 44 n. 5, p. 930-938en_HK
dc.identifier.issn0168-8278en_HK
dc.identifier.urihttp://hdl.handle.net/10722/143607-
dc.description.abstractBackground/Aims: Mutations in SLC25A13, encoding the mitochondrial aspartate-glutamate carrier citrin, cause adult-onset type II citrullinemia (CTLN2) in humans. We have previously reported that although citrin-knockout (Ctrn-/-) mice fail to display symptoms of CTLN2, liver perfusion revealed a deficit in ureogenesis from ammonia accompanied by an increase in the perfusate lactate-to-pyruvate (L/P) ratio. The present study explores the effects of pyruvate, aspartate and citrate on improving the abnormalities observed in the Ctrn-/- liver. Methods: We measured the rate of ureogenesis from ammonium chloride using the liver-perfusion system. Results: Pyruvate infusion lowered the L/P ratio and corrected the deficit in ureogenesis in the Ctrn-/- liver. This effect was found to be dose-dependent in both instances. Phenazine methosulfate, a cytosolic oxidant, also improved the rate of ureogenesis in the Ctrn-/- liver and led to a fall in the L/P ratio. The addition of aspartate or citrate did not change either the rate of ureogenesis or the L/P ratio in the Ctrn-/- liver. Conclusions: Citrin deficiency disturbs urea synthesis primarily as a result of an elevated cytosolic NADH/NAD+ ratio owing to limited reoxidation of reducing equivalents. Clinically, pyruvate may have a therapeutic benefit for CTLN2 patients. © 2005 European Association for the Study of the Liver.en_HK
dc.languageeng-
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/jhepen_HK
dc.relation.ispartofJournal of Hepatologyen_HK
dc.subjectAdult-onset type II citrullinemiaen_HK
dc.subjectArgininosuccinate synthetaseen_HK
dc.subjectCitrin deficiencyen_HK
dc.subjectHyperammonemiaen_HK
dc.subjectPyruvateen_HK
dc.subjectRedox stateen_HK
dc.subjectUreogenesisen_HK
dc.subject.meshAmmonia - metabolism-
dc.subject.meshCalcium-Binding Proteins - genetics-
dc.subject.meshCitrullinemia - drug therapy - genetics - metabolism-
dc.subject.meshOrganic Anion Transporters - genetics-
dc.subject.meshPyruvic Acid - pharmacology-
dc.titlePyruvate ameliorates the defect in ureogenesis from ammonia in citrin-deficient miceen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0168-8278&volume=44&issue=5&spage=930&epage=938&date=2006&atitle=Pyruvate+ameliorates+the+defect+in+ureogenesis+from+ammonia+in+citrin-deficient+mice-
dc.identifier.emailTsui, LC: tsuilc@hkucc.hku.hken_HK
dc.identifier.authorityTsui, LC=rp00058en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.jhep.2005.09.018en_HK
dc.identifier.pmid16458993en_HK
dc.identifier.scopuseid_2-s2.0-33645810180en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33645810180&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume44en_HK
dc.identifier.issue5en_HK
dc.identifier.spage930en_HK
dc.identifier.epage938en_HK
dc.identifier.isiWOS:000237327800014-
dc.publisher.placeNetherlandsen_HK
dc.identifier.scopusauthoridMoriyama, M=7201454259en_HK
dc.identifier.scopusauthoridLi, MX=37069508900en_HK
dc.identifier.scopusauthoridKobayashi, K=7407127141en_HK
dc.identifier.scopusauthoridSinasac, DS=7801388288en_HK
dc.identifier.scopusauthoridKannan, Y=6701564035en_HK
dc.identifier.scopusauthoridIijima, M=7201773787en_HK
dc.identifier.scopusauthoridHoriuchi, M=7202777818en_HK
dc.identifier.scopusauthoridTsui, LC=7102754167en_HK
dc.identifier.scopusauthoridTanaka, M=7408419834en_HK
dc.identifier.scopusauthoridNakamura, Y=7406389714en_HK
dc.identifier.scopusauthoridSaheki, T=7005678417en_HK

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