In vitro synthesis of oleoylglycine by cytochrome c points to a novel pathway for the production of lipid signaling molecules.
Long chain fatty acyl glycines represent a new class of signaling molecules whose biosynthetic pathway is unknown. Here we report that cytochrome c catalyzes the formation of oleoylglycine from oleoyl-CoA and glycine, in the presence of hydrogen peroxide. The identity of oleoylglycine product was confirmed by isotope labeling and fragmentation mass spectrometry. Synthesis of oleoylglycine by cytochrome c was dependent upon substrate concentration and time. Other heme-containing proteins, myoglobin and hemoglobin, did not catalyze oleoylglycine synthesis. The functional properties of the reaction closely resemble those observed for the ability of cytochrome c to mediate the synthesis of oleamide from oleoyl-CoA and ammonia, in the presence of hydrogen peroxide (Driscoll, W. J., Chaturvedi., S., and Mueller, G. P. (2007) J. Biol. Chem. 282). The ability of cytochrome c to catalyze the formation of oleoylglycine experimentally indicates the potential importance of cytochrome c as a novel mechanism for the generation of long chain fatty acyl glycine messengers in vivo.
Mueller
Gregory P
GP
Department of Anatomy, Physiology, and Genetics, F. Edward Hebert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA. gmueller@usuhs.mil
Driscoll
William J
WJ
D000214:Acyl Coenzyme A / Q000737:chemistry*; D000818:Animals; D002855:Chromatography, Thin Layer; D045304:Cytochromes c / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000737:chemistry*; D006418:Heme / Q000737:chemistry*; D006454:Hemoglobins / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D008055:Lipids / Q000737:chemistry*; D013058:Mass Spectrometry / Q000379:methods; D008954:Models, Biological; D009211:Myoglobin / Q000378:metabolism; D009829:Oleic Acids / Q000096:biosynthesis / Q000737:chemistry*; D051381:Rats; D015398:Signal Transduction
D000214:Acyl Coenzyme A; D005227:Fatty Acids; D006454:Hemoglobins; D008055:Lipids; D009211:Myoglobin; D009829:Oleic Acids; C522577:oleoylglycine; C017585:oleoyl-coenzyme A; D006418:Heme; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D005998:Glycine