File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

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?
Abstract
Background/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
2013 Impact Factor: 10.401
ISI Accession Number ID
References

 

Author Affiliations
  1. Kagoshima University Faculty of Medicine
  2. Tokyo Metropolitan Institute of Gerontology
  3. Osaka Prefecture University
  4. Hospital for Sick Children University of Toronto
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

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats