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More Than One HMG-CoA Lyase: The Classical Mitochondrial Enzyme Plus the Peroxisomal and the Cytosolic Ones

1
Unit of Clinical Genetics and Functional Genomics, Department of Pharmacology-Physiology, School of Medicine, University of Zaragoza, CIBERER-GCV02 and ISS-Aragon, E-50009 Zaragoza, Spain
2
Molecular Modelling Group, Center for Molecular Biology “Severo Ochoa” (CSIC-UAM), Cantoblanco, E-28049 Madrid, Spain
3
Department of Paediatrics, Hospital Clínico Universitario “Lozano Blesa”, E-50009 Zaragoza, Spain
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(24), 6124; https://doi.org/10.3390/ijms20246124
Received: 1 November 2019 / Revised: 27 November 2019 / Accepted: 29 November 2019 / Published: 4 December 2019
(This article belongs to the Section Molecular Endocrinology and Metabolism)
There 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. View Full-Text
Keywords: HMG-CoA lyase; HMGCL; HMGCLL1; ketone bodies; 3-hydroxy-3-methylglutaric aciduria HMG-CoA lyase; HMGCL; HMGCLL1; ketone bodies; 3-hydroxy-3-methylglutaric aciduria
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Arnedo, M.; Latorre-Pellicer, A.; Lucia-Campos, C.; Gil-Salvador, M.; Antoñanzas-Peréz, R.; Gómez-Puertas, P.; Bueno-Lozano, G.; Puisac, B.; Pié, J. More Than One HMG-CoA Lyase: The Classical Mitochondrial Enzyme Plus the Peroxisomal and the Cytosolic Ones. Int. J. Mol. Sci. 2019, 20, 6124.

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