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Publication : Sequence comparison of human and mouse 2-amino-3-ketobutyrate coenzyme A ligases

First Author  Edgar AJ Year  1999
Journal  J Pathol Volume  187
Issue  Suppl Pages  21A (Abstr.)
Mgi Jnum  J:60098 Mgi Id  MGI:1352742
Citation  Edgar AJ, et al. (1999) Sequence comparison of human and mouse 2-amino-3-ketobutyrate coenzyme A ligases. J Pathol 187(Suppl):21A (Abstr.)
abstractText  Full text of Abstract: Sequence comparison of human and mouse 2-amino-3-ketobutyrate coenzyme A ligase. A.J. Edgar, J.M. Polak. Department of Histochemistry, Imperial College School of Medicine, Hammersmith Campus, London, United Kingdom. Differential display was used to identify changes in gene expression associated with emphysema. A novel human cDNA related to the Escherichia coli 2-amino-3-ketobutyrate coenzyme A ligase (KBL) gene was upregulated in emphysema. Using bioinformatics the mouse KBL cDNA sequence was obtained. Conversion of L-threonine to glycine in prokaryotes and eukaryotes is a two step biochemical pathway involving L-threonine dehydrogenase and 2-amino-3-ketobutyrate coenzyme A ligase. The genes encoding these enzymes have been described only in prokaryotes. The 1.5 kbase KBL transcript encodes proteins of 419 and 416 residues in human and mouse respectively. The mouse protein has 89% identity with the human protein, and both having 54% identity with the E. coli protein. Both human and mouse proteins have an amino-terminus mitochondrial import sequence making them larger than the E. coli protein. In rats on normal feed, 87% of the bodyÕs enzymatic activity along this biochemical pathway has been estimated to occur in the liver. Human KBL mRNA was found to be expressed more in heart, brain, liver and pancreas than lung, with little occurring in placenta. This suggests that the pathway has a wider tissue distribution than previously thought. The widely varying levels of KBL mRNA expression in different tissues suggests tissue-specific regulation and is not typical of a housekeeping gene. This work was supported by the Julia Polak Lung Transplant Fund and GlaxoWellcome.
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