Creatine kinase muscle type specifically interacts with saturated fatty acid- and/or monounsaturated fatty acid-containing phosphatidic acids.

Abstract

Diacylglycerol kinase (DGK) δ, which is a key enzyme in the pathogenesis of type 2 diabetes (T2D), preferentially generates saturated fatty acid (SFA)- and/or monounsaturated fatty acid (MUFA)-containing phosphatidic acids (PAs) such as 16:0/16:0-PA and 16:0/18:1-PA, but not polyunsaturated fatty acid (PUFA)-containing PAs, in glucose-stimulated myoblast cells. Here, we searched for the target proteins of 16:0/16:0-PA in the mouse skeletal muscle and identified an energy metabolizing enzyme, creatine kinase muscle type (CKM), which is correlated with T2D. CKM bound to 16:0/16:0-PA with the highest affinity (dissociation constant: 2.0 μM) among all the PA-binding proteins reported thus far. Intriguingly, CKM preferentially interacted with SFA- and/or MUFA-containing PAs, but not with PUFA-containing PAs. Notably, CKM exclusively interacted with PA, whereas the protein did not bind to other lipids such as diacylglycerol, phosphatidylserine, phosphatidylglycerol, phosphatidylinositol, phosphatidylinositol (3,4,5)-trisphosphate and cardiolipin. Taken together, these results demonstrate that CKM is a very unique PA-binding protein that possesses exceedingly high affinity for PA, exceptional preference for SFA/MUFA-PA and extremely high specificity to PA and suggest that SFA/MUFA-PAs produced by DGKδ are novel regulators of CKM function.

• Authors: Fumi Hoshino, Chiaki Murakami, Hiromichi Sakai, Mamoru Satoh, Fumio Sakane
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 513 Issue 4 Pg. 1035-1040 (06 11 2019) ISSN: 1090-2104 [Electronic] United States
• PMID: 31010675 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Fatty Acids
• Fatty Acids, Monounsaturated
• Phosphatidic Acids
• Diacylglycerol Kinase
• Creatine Kinase

Topics

• Animals
• Creatine Kinase (metabolism)
• Diabetes Mellitus, Type 2 (enzymology)
• Diacylglycerol Kinase (metabolism)
• Fatty Acids (chemistry, metabolism)
• Fatty Acids, Monounsaturated (chemistry, metabolism)
• Mice
• Muscle, Skeletal (enzymology)
• Phosphatidic Acids (metabolism)
• Protein Binding