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Bistability in fatty-acid oxidation resulting from substrate inhibition, 2021, Bakker et al

Discussion in 'Other health news and research' started by Midnattsol, Jul 16, 2022.

  1. Midnattsol

    Midnattsol Moderator Staff Member

    In this study we demonstrated through analytic considerations and numerical studies that the mitochondrial fatty-acid β-oxidation can exhibit bistable-hysteresis behavior. In an experimentally validated computational model we identified a specific region in the parameter space in which two distinct stable and one unstable steady state could be attained with different fluxes. The two stable states were referred to as low-flux (disease) and high-flux (healthy) state. By a modular kinetic approach we traced the origin and causes of the bistability back to the distributive kinetics and the conservation of CoA, in particular in the last rounds of the β-oxidation. We then extended the model to investigate various interventions that may confer health benefits by activating the pathway, including (i) activation of the last enzyme MCKAT via its endogenous regulator p46-SHC protein, (ii) addition of a thioesterase (an acyl-CoA hydrolysing enzyme) as a safety valve, and (iii) concomitant activation of a number of upstream and downstream enzymes by short-chain fatty-acids (SCFA), metabolites that are produced from nutritional fibers in the gut. A high concentration of SCFAs, thioesterase activity, and inhibition of the p46Shc protein led to a disappearance of the bistability, leaving only the high-flux state. A better understanding of the switch behavior of the mitochondrial fatty-acid oxidation process between a low- and a high-flux state may lead to dietary and pharmacological intervention in the treatment or prevention of obesity and or non-alcoholic fatty-liver disease.

    Hutan, Peter Trewhitt, merylg and 3 others like this.
  2. Midnattsol

    Midnattsol Moderator Staff Member

    I was looking for something else and came across this. I've only read the abstract, but will look at it more later as two different states of flux through beta-oxidation seems interesting, especially in light of other hypotheses on metabolic traps the body can get stuck in. Obviously from a dietitian's standpoint it's also interesting to read about potential benefits of fibre :p
  3. Arnie Pye

    Arnie Pye Senior Member (Voting Rights)

    For anyone (like me) who has never heard of bistability...


    Edit : One reason I had a problem with bistability is because I was reading the first syllable as if it was the start of "Bisto" i.e. a gravy powder common in the UK.

    Then I realised it should be pronounced bi - stability, which made it sound a lot more sensible and a lot more memorable.

    :banghead::banghead::banghead::banghead: :bag: :oops:
    Last edited: Jul 16, 2022

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