Characterization of splice variants of the genes encoding human mitochondrial HMG-CoA lyase and HMG-CoA synthase, the main enzymes of the ketogenesis pathway
| Autor: | María Teresa Echeverría Arnedo, Mónica Ramos, Paulino Gómez-Puertas, Jan-Jaap Wesselink, Sebastián Menao, Beatriz Puisac, Juan Pié, Ignacio Gimenez, Fausto G. Hegardt, Angeles Pié, Juan C. de Karam, María Concepción Gil-Rodríguez, Feliciano J. Ramos, Núria Casals, María Esperanza Teresa-Rodrigo |
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| Přispěvatelé: | Gobierno de Aragón, Universidad de Zaragoza, Ministerio de Educación y Ciencia (España), Instituto de Salud Carlos III, European Commission, Fundación Ramón Areces |
| Rok vydání: | 2011 |
| Předmět: |
Hydroxymethylglutaryl-CoA Synthase
Blotting Western Ketone Bodies Biology Mitochondrion Real-Time Polymerase Chain Reaction Isozyme Protein Structure Secondary 03 medical and health sciences Exon 0302 clinical medicine Ketogenesis Genetics Humans splice Molecular Biology Gene 030304 developmental biology 0303 health sciences Alternative splicing Computational Biology Oxo-Acid-Lyases HMGCL General Medicine Lyase Molecular biology Biosynthetic Pathways Mitochondria Isoenzymes Alternative Splicing HEK293 Cells Biochemistry Ketone bodies HMGCS2 030217 neurology & neurosurgery |
| Zdroj: | Molecular Biology Reports; Vol 39 Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 1573-4978 |
| Popis: | The genes HMGCS2 and HMGCL encode the two main enzymes for ketone-body synthesis, mitochondrial HMG-CoA synthase and HMG-CoA lyase. Here, we identify and describe possible splice variants of these genes in human tissues. We detected an alternative transcript of HMGCS2 carrying a deletion of exon 4, and two alternative transcripts of HMGCL with deletions of exons 5 and 6, and exons 5, 6 and 7, respectively. All splice variants maintained the reading frame. However, Western blot studies and overexpression measurements in eukaryotic or prokaryotic cell models did not reveal HL or mHS protein variants. Both genes showed a similar distribution of the inactive variants in different tissues. Surprisingly, the highest percentages were found in tissues where almost no ketone bodies are synthesized: heart, skeletal muscle and brain. Our results suggest that alternative splicing might coordinately block the two main enzymes of ketogenesis in specific human tissues Diputación General de Aragón; University of Zaragoza UZ2007-BIO-13); Spanish Ministry of Education and Science ; Instituto de Salud Carlos III (CIBER Fisiopatologıa de la Obesidad y Nutrición); European Union (FP7-223431 ‘‘Divinocell’’ project); Fundación Ramón Areces |
| Databáze: | OpenAIRE |
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