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

Matthew J Kolar, Siddhesh S Kamat, William H Parsons, Edwin A Homan, Tim Maher, Odile D Peroni, Ismail Syed, Karianne Fjeld, Anders Molven, Barbara B Kahn, Benjamin F Cravatt, Alan Saghatelian

Biochemistry 2016 Aug 23

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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.

Citation

Matthew J Kolar, Siddhesh S Kamat, William H Parsons, Edwin A Homan, Tim Maher, Odile D Peroni, Ismail Syed, Karianne Fjeld, Anders Molven, Barbara B Kahn, Benjamin F Cravatt, Alan Saghatelian. Branched Fatty Acid Esters of Hydroxy Fatty Acids Are Preferred Substrates of the MODY8 Protein Carboxyl Ester Lipase. Biochemistry. 2016 Aug 23;55(33):4636-41