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- W3044015075 endingPage "158768" @default.
- W3044015075 startingPage "158768" @default.
- W3044015075 abstract "Phosphatidic acid (PA) consists of various molecular species that have different fatty acyl chains at the sn-1 and sn-2 positions; and consequently, mammalian cells contain at least 50 structurally distinct PA molecular species. However, the different roles of each PA species are poorly understood. In the present study, we attempted to identify dipalmitoyl (16:0/16:0)-PA-binding proteins from mouse skeletal muscle using liposome precipitation and tandem mass spectrometry analysis. We identified L-lactate dehydrogenase (LDH) A, which catalyzes conversion of pyruvate to lactate and is a key checkpoint of anaerobic glycolysis critical for tumor growth, as a 16:0/16:0-PA-binding protein. LDHA did not substantially associate with other phospholipids, such as phosphatidylcholine, phosphatidylserine, phosphatidylglycerol, phosphatidylinositol, phosphoinositides and cardiolipin at physiological pH (7.4), indicating that LDHA specifically bound to PA. Interestingly, 18:0/18:0-, 18:0/20:4- and 18:0/22:6-PA also interacted with LDHA, and their binding activities were stronger than 16:0/16:0-PA at pH 7.4. Moreover, circular dichroism spectrometry showed that 18:0/20:4- and 18:0/22:6-PA, but not 16:0/16:0- or 18:0/18:0-PA, significantly reduced the α-helical structure of LDHA. Furthermore, 18:0/20:4- and 18:0/22:6-PA attenuated LDH activity. Taken together, we demonstrated for the first time that LDHA is a PA-binding protein and is a unique PA-binding protein that is structurally and functionally controlled by associating with 18:0/20:4- and 18:0/22:6-PA." @default.
- W3044015075 created "2020-07-29" @default.
- W3044015075 creator A5018843945 @default.
- W3044015075 creator A5052438029 @default.
- W3044015075 date "2020-10-01" @default.
- W3044015075 modified "2023-09-25" @default.
- W3044015075 title "Polyunsaturated fatty acid-containing phosphatidic acids selectively interact with L-lactate dehydrogenase A and induce its secondary structural change and inactivation" @default.
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- W3044015075 doi "https://doi.org/10.1016/j.bbalip.2020.158768" @default.
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- W3044015075 hasPublicationYear "2020" @default.
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