Activation of Fatty Acids by a Guanosine Triphosphate-specific Thiokinase from Liver Mitochondria.

In the initial studies of Lehninger (1) on the oxidation of octanoate by rat liver mitochondria, it was noted that oc-ketoglutarate possessed a unique property in regard to its role as a co-oxidant. Whereas all other intermediates of the tricarboxylic acid cycle t,est,ed for sparking activity required the simultaneous addition of adenosine monophosphate, a-ketoglutarate functioned efficiently by itself. It was suggested that ol-ketoglutarate may give rise to a nonadenylate intermediate that could activate fatty acids. In the present investigation, a search was made for a GTPlinked fatty acyl kinase in liver mitochondria. A GTP-specific enzyme system was found that catalyzes the following reaction (Equation 4) (8).