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Transporter Reference Concentration fmol/ug protein to umol/L: Scaling factor? #235

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krinaj opened this Issue Oct 12, 2018 · 3 comments

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@krinaj

krinaj commented Oct 12, 2018

Hi all,

I want to add Reference Concentration of SLCO1B1 (OATP1B1) transporter protein level in the human I want to use for some simulations. I found the following paper (open access, so attaching) with some values of liver protein levels in fmol/ug of surface protein. I don't know what would be scaling factor for surface protein in liver, may be something like ug surface protein per gram liver or similar? Any other ideas how to get transporter reference concentrations in liver?

I guess my last option will be to fit.

Many thanks,
Krina

Badee_2015_OATP_expression.pdf

@StephanSchaller

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StephanSchaller commented Oct 12, 2018

@PavelBal any insights based on you recent protein expression research?

@PavelBal

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PavelBal commented Oct 14, 2018

Hi Krina,

I found two values of total membrane protein abundances in the liver - 35.8 and 41.6 mg membrane protein per gram liver [1]. There exist concerns whether reliable separation of membrane protein is possible, so the values have to be treated with caution [2].

If you come across another values (or similar values from other publications), please share them with us. At some point, we will have to decide on a "standard" value when implementing a protein abundance database for PKSim.

[1] Harwood, M. D., Neuhoff, S., Carlson, G. L., Warhurst, G. & Rostami-Hodjegan, A. Absolute abundance and function of intestinal drug transporters: a prerequisite for fully mechanistic in vitro-in vivo extrapolation of oral drug absorption: PROTEIN ABUNDANCE FOR INTESTINAL TRANSPORTERS WITHIN A PBPK FRAMEWORK. Biopharmaceutics & Drug Disposition 34, 2–28 (2013).

[2] Kumar, V. et al. Quantitative Transporter Proteomics by Liquid Chromatography with Tandem Mass Spectrometry: Addressing Methodologic Issues of Plasma Membrane Isolation and Expression-Activity Relationship. Drug Metabolism and Disposition 43, 284–288 (2014).

Best
Pavel

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krinaj commented Oct 14, 2018

Very useful. Thanks, Pavel and Stephan.

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