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Very interesting model

Posted by seaton on 01 Oct 2013 at 12:06 GMT

Congratulations on this interesting model which allows testing of various scenarios. I would be interested in knowing how well the estimated individual concentations of long-chain CoA esters correspond to those measured during beta-oxidation in rat liver mitochondria.

I do have some reservations about taking many of the kinetic characteristics from Kohn and Garfinkel's paper. In particular, they had set CPT2 having a Km for CoASH of 30uM, whereas I think a better experimental estimate is 121uM (Biochem J. 1993 Sep 15;294 ( Pt 3):645-51. Comparison of the active sites of the purified carnitine acyltransferases from peroxisomes and mitochondria by using a reaction-intermediate analogue.
Nic a' Bháird N, Kumaravel G, Gandour RD, Krueger MJ, Ramsay RR.). Having a markedly higher Km for CoASH CPT2 than the CoASH Kms for the thiolases (low uM) and pyruvate dehydrogenase (20uM) would act to prevent excessive acylation of the intramitochondrial CoA pool. Just changing this single parameter might change the concentrations of carnitine esters quite a bit.

Nevertheless, great job!

No competing interests declared.