| Metabolic flux rearrangement in the amino acid metabolism reduces ammonia stress in the α(1)-antitrypsin producing human AGE1.HN cell line. | |
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MedLine Citation:
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PMID: 22289170 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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This study focused on metabolic changes in the neuronal human cell line AGE1.HN upon increased ammonia stress. Batch cultivations of α(1)-antitrypsin (A1AT) producing AGE1.HN cells were carried out in media with initial ammonia concentrations ranging from 0mM to 5mM. Growth, A1AT production, metabolite dynamics and finally metabolic fluxes calculated by metabolite balancing were compared. Growth and A1AT production decreased with increasing ammonia concentration. The maximum A1AT concentration decreased from 0.63g/l to 0.51g/l. Central energy metabolism remained relatively unaffected exhibiting only slightly increased glycolytic flux at high initial ammonia concentration in the medium. However, the amino acid metabolism was significantly changed. Fluxes through transaminases involved in amino acid degradation were reduced concurrently with a reduced uptake of amino acids. On the other hand fluxes through transaminases working in the direction of amino acid synthesis, i.e., alanine and phosphoserine, were increased leading to increased storage of excess nitrogen in extracellular alanine and serine. Glutamate dehydrogenase flux was reversed increasingly fixing free ammonia with increasing ammonia concentration. Urea production additionally observed was associated with arginine uptake by the cells and did not increase at high ammonia stress. It was therefore not used as nitrogen sink to remove excess ammonia. The results indicate that the AGE1.HN cell line can adapt to ammonia concentrations usually present during the cultivation process to a large extent by changing metabolism but with slightly reduced A1AT production and growth. |
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Authors:
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Christian Priesnitz; Jens Niklas; Thomas Rose; Volker Sandig; Elmar Heinzle |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-25 |
Journal Detail:
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Title: Metabolic engineering Volume: - ISSN: 1096-7184 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-31 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9815657 Medline TA: Metab Eng Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012 Elsevier Inc. All rights reserved. |
Affiliation:
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Biochemical Engineering Institute, Saarland University, D-66123 Saarbrücken, Germany. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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