RELIEF OF PALMITYL CoA INHIBITION OF CITRATE SYNTRASE BY LONG-CRAINACYLCABNITINE DEBIVATNEs+

We have recently observed that (+)-palmitylcarnitine stimulates fatty acid synthesis by liver supernatant fractions prepared from either fed or starved rats (Fritz and Hsu, 1966). One of the possible mechanisms by which (+)-palmitylcarnitine could restore lipogenesis by livers from starved animals to normal levels would include a release from an inhibition of fatty acid synthesis by a "physiological" inhibitor such as palmityl CoA (Bortz and Lynen, 1963), or a less well defined microsomal entity described by Masoro et al (1962). The concentrations in liver of both palmityl CoA snd the microsomal inhibitor are reported by these authors to rise during starvation. Since palmityl CoA is also an inhibitor of citrate synthase activity (Wielsnd et al, 1@64; Tubbs, 1963; Srere, 1965), and since citrate is involved in several aspects of fatty acid metabolism (Srere and Bhaduri, 1962; Martin and Vagelos, 1962), it appeared that this reaction would be an interesting one to investigate in relation to the above possibility. Accordingly, citrate synthase (E. C. 4. 1. 3.7) activity was asssyed in the presence and absence of palmityl CoA, and various chain-length acylcarnitine derivatives were incubated with the enzyme during these procedures. Results to be presented demonstrate that long-chain 0-acylcarnitine derivatives protect citrate synthase from inhibition by palmityl CoA if they are incubated with enzyme during the incubation period prior to oxaloacetate addition. METRODS Citrate synthase was purchased from Boehringer Mannheim Corporation, and activity was assayed by following the absorbance decrease at 232 w indicative of thioester cleavage after the addition of oxaloacetate to cuvettes containing acetyl CoA and enzyme together with various components