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Synthesis of endogenous protein in arterial/vernous compartment?? #231
I want to introduce an endogenous protein into a PBPK model. I have observations of this protein in venous plasma.
Any solutions or ideas??
Thank in advance,
you can introduce a formation process generating the endogenous protein in a (or all) plasma compartment(s) within MoBi. Then - together with the generic endosomal CL and any additional CL process you define - a turnover of the endogenous protein would result.
All the best,
I have a file attached with an IgM administration to a human individual (as a protein example). What I want to do here exemplarily is to set up an IgM formation process to obtain a certain baseline IgM concentration in plasma. So that IgM is administered "on top" of this IgM baseline.
How do I do that? Where do I have to define the Synthesis (reactions building block?)? How do I have to choose the parameter paths? How do I have to define the IgM synthesis rate to achieve a specific IgM baseline in plasma If the IgM clearance is only driven by the endosomal uptake rate?
I guess these are a lot of questions... but I am quite lost at the moment....
Instead of using this mechanistic approach I thought of simply adding a baseline IgM concentration to the plasma observer. But I do not like that idea - or what do you think about that?
Many thanks in advance
we did sth. very similar for an explicit Albumin Model we developed.
thank you for your response!
on this point:
You create (yes, in the reactions building block) a reaction somewhere, where IgM is produced (Bone(marrow)?)(check literature for synthesis rate).
How can I confine a reaction to Bone plasma?
Thanks in advance,
yes, that helps absolutely!! :)
What I aim at is a IgM forming reaction, for which I can define a Baseline IgM concentration (with standard deviation) in a population simulation. The Synthesis rate should be calculated for each individual's baseline in the population. Something in the form of ksyn = baseline * kdeg. Do you have some suggestion on how to write down the reaction in MoBI?
My baseline amount of 0.02 µmol results in a peripheral venous blood conc. of IgM of 0.47 µmol/L (dashed line):
@StephanSchaller "Asses the base concentration of IgM: if the baseline is too low/high, you can either adjust synthesis rate, FcRn binding or introduce additional proteolysis (another reaction for degradation). But make sure you also et the right half-life (half-life is around 3 weeks? ). You can asses half-life visually, when turning of synthesis and simulate an IgM bolus."
Many thanks in advance!!