Characterization of a novel HMG-CoA lyase enzyme with a dual location in endoplasmic reticulum and cytosol.

ARNEDO M.; MENAO S; BEATRIZ PUISAC; MARÍA E. TERESA-RODRIGO; MARÍA C. GIL-RODRÍGUEZ; EDUARDO LÓPEZ-VIÑAS; PAULINO GÓMEZ-PUERTAS; NURIA CASALS; CASALE CESAR; FAUSTO G. HEGARDT; PIE-JUSTE J

JLR PAPERS IN PRESS

AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

Lugar: Bethesda, Maryland; Año: 2012 vol. 53 p. 2046 - 2056

0022-2275

A novel lyase activity enzyme is characterized for the fi rst time: HMG-CoA lyase-like1 (er-cHL), which is a close homolog of mitochondrial HMG-CoA lyase (mHL). Initial data show that there are nine mature transcripts for the novel gene HMGCLL1 , although none of them has all its exons. The most abundant transcript is called ?variant b,? and it lacks exons 2 and 3. Moreover, a three-dimensional model of the novel enzyme is proposed. Colocalization studies show a dual location of the er-cHL in the endoplasmic reticulum (ER) and cytosol, but not in mitochondria or peroxisomes. Furthermore, the dissociation experiment suggests that it is a nonendoplasmic reticulum integral membrane protein. The kinetic parameters of er-cHL indicate that it has a lower V max and a higher substrate affi nity than mHL. Protein expression and lyase activity were found in several tissues, and were particularly strong in lung and kidney. The occurrence of er-cHL in brain is surprising, as mHL has not been found there. Although mHL activity is clearly associated with energy metabolism, the results suggest that er-cHL is more closely related to another metabolic function, mostly at the pulmonary and brain level. ?