Document Detail

Variable peroxisomal and mitochondrial targeting of alanine: glyoxylate aminotransferase in mammalian evolution and disease.
MedLine Citation:
PMID:  9136629     Owner:  NLM     Status:  MEDLINE    
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.
C J Danpure
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
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:
Created Date:  1997-06-26     Completed Date:  1997-06-26     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8510851     Medline TA:  Bioessays     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  317-26     Citation Subset:  IM    
MRC Laboratory for Molecular Cell Biology, University College London, UK.
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MeSH Terms
Alanine Transaminase / metabolism*
Biological Transport
Cytosol / enzymology
Energy Metabolism
Enzyme Induction
Evolution, Molecular
Glucose / metabolism
Glyoxylates / metabolism
Hyperoxaluria / enzymology*,  genetics
Mammals / metabolism*
Microbodies / enzymology*
Mitochondria / enzymology*
Polymorphism, Genetic
Protein Sorting Signals / physiology
Selection, Genetic
Species Specificity
Reg. No./Substance:
0/Glyoxylates; 0/Protein Sorting Signals; 298-12-4/glyoxylic acid; 50-99-7/Glucose; EC 2.6.1.-/Transaminases; EC Transaminase; EC transaminase

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