Unfinished Business #4: modelling β-oxidation

I have a long-running collaboration with Bernard Corfe, modelling metabolism of dietary fibres in the gut. These – otherwise indigestible – carbohydrates are first fermented by bacteria in the colon to form short-chain fatty acids: acetate (C2), propionate (C3) and butyrate (C4). The fatty acids are then taken up by colonocytes, and processed in their mitochondria using β-oxidation. It is a major source of energy in humans, and deficiencies in dietary fibre metabolism cause a number of diseases.

Of course we’d like to model this by fully characterising all the enzymes in colonocytes, as Manchester did for yeast glycolysis and PPP. But, for those not fortunate enough to have a £6.4M grant, we can get a long way through enriching the model structure (below) with typical parameter values.

You can grab an SBML version of this model from models.u003f.com/box.zip: have a play. Having a kinetic model means we can run analyses such as MCA. And running such analyses allows us to find out that butyrate uptake is the key controller of both β-oxidation and glycolysis.

Interaction between β-oxidation and glycolysis in colonocytes, presented in SBGN format.
Competition occurs between the short-chain fatty acids and lactate for transporter use.


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