Branched Fatty Acid Esters of Hydroxy Fatty Acids Are Preferred Substrates of the MODY8 Protein Carboxyl Ester Lipase

被引：64

作者：

Kolar, Matthew J. ^{[1
]}

Kamat, Siddhesh S. ^{[2
]}

Parsons, William H. ^{[2
]}

Homan, Edwin A. ^{[3
,9
]}

Maher, Tim ^{[3
,10
]}

Peroni, Odile D. ^{[4
]}

Syed, Ismail ^{[4
]}

Fjeld, Karianne ^{[5
,6
]}

Molven, Anders ^{[7
,8
]}

Kahn, Barbara B. ^{[4
]}

Cravatt, Benjamin F. ^{[2
]}

Saghateliann, Alan ^{[1
]}

机构：

[1] Salk Inst Biol Studies, Helmsley Ctr Genom Med, Peptide Biol Labs, La Jolla, CA 92037 USA

[2] Scripps Res Inst, Skaggs Inst Chem Biol, Dept Physiol Chem, La Jolla, CA 92037 USA

[3] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA

[4] Harvard Med Sch, Div Endocrinol Diabet & Metab, Dept Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA

[5] Univ Bergen, KG Jebsen Ctr Diabet Res, Dept Clin Sci, N-5021 Bergen, Norway

[6] Haukeland Hosp, Ctr Med Genet & Mol Med, N-5021 Bergen, Norway

[7] Univ Bergen, Dept Clin Med, Gade Lab Pathol, N-5021 Bergen, Norway

[8] Haukeland Hosp, Dept Pathol, N-5021 Bergen, Norway

[9] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA

[10] Massachusetts Gen Hosp, Boston, MA 02114 USA

来源：

BIOCHEMISTRY | 2016年 / 55卷 / 33期

基金：

美国国家卫生研究院;

关键词：

SALT-STIMULATED LIPASE; CHOLESTERYL ESTER; PANCREATIC LIPASE; HUMAN-MILK; CEL; ABSORPTION; MUTATIONS;

D O I：

10.1021/acs.biochem.6b00565

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A recently discovered class of endogenous mammalian lipids, branched fatty acid esters of hydroxy fatty acids (FAHFAs), possesses anti-diabetic and anti-inflammatory activities. Here, we identified and validated carboxyl ester lipase (CEL), a pancreatic enzyme hydrolyzing cholesteryl esters and other dietary lipids, as a FAHFA hydrolase. Variants of CEL have been linked to maturity-onset diabetes of the young, type 8 (MODY8), and to chronic pancreatitis. We tested the FAHFA hydrolysis activity of the CEL MODY8 variant and found a modest increase in activity as compared with that of the normal enzyme. Together, the data suggest that CEL might break down dietary FAHFAs.

引用

页码：4636 / 4641

页数：6

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