| Variable peroxisomal and mitochondrial targeting of alanine: glyoxylate aminotransferase in mammalian evolution and disease. | |
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MedLine Citation:
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PMID: 9136629 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Under the putative influence of dietary selection pressure, the subcellular distribution of alanine:glyoxylate aminotransferase 1 (AGT) has changed on many occasions during the evolution of mammals. Depending on the particular species, AGT can be found either in peroxisomes or mitochondria, or in both peroxisomes and mitochondria. This variable localization depends on the differential expression of N-terminal mitochondrial and C-terminal peroxisomal targeting sequences by the use of alternative transcription and translation initiation sites. AGT is peroxisomal in most humans, but it is mistargeted to the mitochondria in a subset of patients suffering from the rare hereditary disease primary hyperoxaluria type 1. Mistargeting is due to the unlikely combination of a normally occurring polymorphism that generates a functionally weak mitochondrial targeting sequence and a disease-specific mutation which, in combination with the polymorphism, inhibits AGT dimerization. The mechanisms by which AGT can be targeted differentially to peroxisomes and/or mitochondria highlight the different molecular requirements for protein import into these two organelles. |
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Authors:
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C J Danpure |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Review |
Journal Detail:
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Title: BioEssays : news and reviews in molecular, cellular and developmental biology Volume: 19 ISSN: 0265-9247 ISO Abbreviation: Bioessays Publication Date: 1997 Apr |
Date Detail:
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Created Date: 1997-06-26 Completed Date: 1997-06-26 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 8510851 Medline TA: Bioessays Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 317-26 Citation Subset: IM |
Affiliation:
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MRC Laboratory for Molecular Cell Biology, University College London, UK. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Alanine Transaminase
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metabolism* Animals Biological Transport Catalysis Cytosol / enzymology Diet Dimerization Energy Metabolism Enzyme Induction Evolution, Molecular Glucose / metabolism Glyoxylates / metabolism Humans Hyperoxaluria / enzymology*, genetics Mammals / metabolism* Microbodies / enzymology* Mitochondria / enzymology* Polymorphism, Genetic Protein Sorting Signals / physiology Selection, Genetic Species Specificity Transaminases* |
| Chemical | |
Reg. No./Substance:
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0/Glyoxylates; 0/Protein Sorting Signals; 298-12-4/glyoxylic acid; 50-99-7/Glucose; EC 2.6.1.-/Transaminases; EC 2.6.1.2/Alanine Transaminase; EC 2.6.1.44/Alanine-glyoxylate transaminase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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