More than one HMG-CoA Lyase: The classical mitochondrial enzyme plus the peroxisomal and the cytosolic ones

Arnedo, María (Universidad de Zaragoza) ; Latorre-Pellicer, Ana (Universidad de Zaragoza) ; Lucia-Campos, Cristina (Universidad de Zaragoza) ; Gil-Salvador, Marta ; Antoñanzas-Peréz, Rebeca (Universidad de Zaragoza) ; Gómez-Puertas, Paulino ; Bueno-Lozano, Gloria (Universidad de Zaragoza) ; Puisac, Beatriz (Universidad de Zaragoza) ; Pié, Juan (Universidad de Zaragoza)

Resumen: 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.

Idioma: Inglés

DOI: 10.3390/ijms20246124

Año: 2019

Publicado en: International Journal of Molecular Sciences 20, 24 (2019), 6124 [14 pp.]
ISSN: 1661-6596

Factor impacto JCR: 4.556 (2019)

Categ. JCR: BIOCHEMISTRY & MOLECULAR BIOLOGY rank: 74 / 296 = 0.25 (2019) - Q1 - T1
Categ. JCR: CHEMISTRY, MULTIDISCIPLINARY rank: 48 / 176 = 0.273 (2019) - Q2 - T1

Factor impacto SCIMAGO: 1.317 - Medicine (miscellaneous) (Q1) - Physical and Theoretical Chemistry (Q1) - Computer Science Applications (Q1) - Inorganic Chemistry (Q1) - Spectroscopy (Q1) - Organic Chemistry (Q1) - Molecular Biology (Q2) - Catalysis (Q2)

Financiación: info:eu-repo/grantAgreement/ES/DGA/B32-17R
Financiación: info:eu-repo/grantAgreement/ES/MICINN/RTI2018-094434-B-100
Financiación: info:eu-repo/grantAgreement/ES/MINECO/RTC-2017-6494-1

Tipo y forma: Revisión (Versión definitiva)

Área (Departamento): Área Fisiología (Dpto. Farmacología y Fisiolog.)
Área (Departamento): Proy. investigación DUA (Dpto. Farmacología y Fisiolog.)
Área (Departamento): Área Pediatría (Dpto. Pediatría Radiol.Med.Fís)