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Title

More than one hmg-coa lyase: The classical mitochondrial enzyme plus the peroxisomal and the cytosolic ones

AuthorsArnedo, María; Latorre-Pellicer, Ana; Lucia-Campos, Cristina; Gil-Salvador, Marta; Antoñanzas-Peréz, Rebeca; Gómez-Puertas, Paulino ; Bueno-Lozano, Gloria; Puisac, Beatriz; Pié, Juan
KeywordsHMG-CoA lyase
HMGCL
HMGCLL1
Ketone bodies
3-hydroxy-3-methylglutaric aciduria
Issue Date4-Dec-2019
PublisherMolecular Diversity Preservation International
CitationInternational Journal of Molecular Sciences 20 (2019)
AbstractThere are three human enzymes with HMG-CoA lyase activity that are able to synthesize ketone bodies in different subcellular compartments. The mitochondrial HMG-CoA lyase was the first to be described, and catalyzes the cleavage of 3-hydroxy-3-methylglutaryl CoA to acetoacetate and acetyl-CoA, the common final step in ketogenesis and leucine catabolism. This protein is mainly expressed in the liver and its function is metabolic, since it produces ketone bodies as energetic fuels when glucose levels are low. Another isoform is encoded by the same gene for the mitochondrial HMG-CoA lyase (HMGCL), but it is located in peroxisomes. The last HMG-CoA lyase to be described is encoded by a different gene, HMGCLL1, and is located in the cytosolic side of the endoplasmic reticulum membrane. Some activity assays and tissue distribution of this enzyme have shown the brain and lung as key tissues for studying its function. Although the roles of the peroxisomal and cytosolic HMG-CoA lyases remain unknown, recent studies highlight the role of ketone bodies in metabolic remodeling, homeostasis, and signaling, providing new insights into the molecular and cellular function of these enzymes.
Publisher version (URL)http://dx.doi.org/10.3390/ijms20246124
URIhttp://hdl.handle.net/10261/215052
Identifiersdoi: 10.3390/ijms20246124
issn: 1422-0067
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