Shanado, Yuka, Kometani, Motohiko, Uchiyama, Hidefumi, Koizumi, Shinichi and Teno, Naoki (2004) Lysophospholipase I identified as a ghrelin deacylation enzyme in rat stomach. Biochemical and Biophysical Research Communications, 325 (4). pp. 1487-1494. ISSN 0006-291X

Abstract

Ghrelin, discovered in rat stomach as an endogenous growth hormone secretagogue, is octanoylated at the Ser3 residue. Since this octanoylation is essential for the functions of ghrelin, the enzymes that catalyze acylation for ghrelin biosynthesis and deacylation (deactivation step) must be considered as important regulators. We found that rat stomach homogenate contained ghrelin deacylation activity, and we isolated the active fractions by column chromatography. After sequencing and expressing candidate proteins, the ghrelin deacylation enzyme in the stomach was identified as lysophospholipase I (LysoPLA I). The enzyme properties were examined using recombinant rat LysoPLA I expressed in Escherichia coli. K(m) and V(max) values were determined as 6.5 microM and 2.3 micromol/min/mg for ghrelin and 2.2 x 10(2) microM and 0.5 micromol/min/mg for lysophosphatidylcholine (LysoPC), respectively. The deacylation of both substrates was inhibited by methyl arachidonyl fluorophosphonate (MAFP), which is known as an irreversible inhibitor of LysoPLA I. These results reveal that LysoPLA I catalyzes the removal of n-octanoic acid from ghrelin to form des-acyl ghrelin. Identification of the ghrelin deacylation enzyme in the stomach and a deacylation inhibitor will be helpful in investigating ghrelin biosynthesis.

Item Type:	Article
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez... doi:10.1016/j.bbrc.2004.10.193
Additional Information:	author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
Keywords:	Ghrelin; Lysopholipase I; Methyl arachidonyl flourophosphonate; Des-acyl ghrelin; n-Octanoyl group; Rat stomach; Deacylation
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez... doi:10.1016/j.bbrc.2004.10.193
Date Deposited:	14 Dec 2009 13:55
Last Modified:	14 Dec 2009 13:55
URI:	https://oak.novartis.com/id/eprint/713