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Polyunsaturated Fatty Acids (PUFAs) Inhibit Polyisoprenylated Methylated Protein Methyl Esterase (PMPMEase)
Author(s) -
Duverna Randolph,
Taylor Shalina,
Lamango Nazarius S
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.675.3
Subject(s) - polyunsaturated fatty acid , biochemistry , enzyme , methylation , chemistry , eicosapentaenoic acid , esterase , intracellular , fatty acid , gene
Polyisoprenylation is a protein modification with 15 or 20 carbon isoprenes. Polyisoprenylated proteins (PP) undergo S‐adenosyl‐L‐methionine‐dependent methylation of the terminal ‐COOH. PP mediate various intracellular processes such as signaling, cell proliferation, differentiation and apoptosis and mutations of PP are encountered in about 30% of cancers. The methylation by PP methyl transferase (PPMTase) is counteracted by PMPMEase and constitute the only reversible step of the pathway. The relative amounts of the acid and ester forms of PP are determined by the two enzymes. Since PMPMEase and PPMTase may influence functional conformations of PP, a thorough knowledge of these enzymes is essential to the understanding of the significance of PP. Unlike the well studied PPMTase, PMPMEase is less understood. PMPMEase's ability to hydrolyze food‐derived substances has led us to hypothesize a regulatory role of PUFAs on the enzyme activity. A series of saturated and PUFAs were tested for PMPMEase inhibition using an HPLC‐based assay. Shorter chain, more unsaturated, cis fatty acids were the most inhibitory, with an IC 50 of 11.6 μM for eicosapentaenoic acid. The anticancer and other benefits of short chain fatty acids and PUFAs may be related to PMPMEase inhibition given the many putative PP substrates that impact various biochemical events. Supported by NIH/NIGMS/SCORE (GM 08111‐35) & NIH/NCRR (G12 RR0 3020).