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We are doing PBPK modeling for volatile organic compounds, where
Michaelis-Menten metabolism is modeled using the equation
d/dt(Amount metabolized) = Vmax * C / ( KM + C )
Here, Vmax is the maximum velocity of metabolism, KM is the
Michelis-Menten constant, and C is the concentration which drives
metabolism.
In the published models (eg Styrene, Chloroform, ...) the authors use
the concentration in venous blood leaving the liver. We wonder if the
concentration in liver tissue would not be the more plausible choice,
as the enzymes are present in the liver cells rather than in blood.
Is there a reason that so far the venous blood concentration was used?
Which concentration should we use?
Thanks in advance,
Hans Mielke
Dr. Hans Mielke
Bundesinstitut für Risikobewertung
Thielallee 88-92, D - 14195 Berlin
Tel. 01888 412 3969 Fax 3970
[An interesting question. To some extent it depends on how you
determined Vm/Km. If they are derived from cell culture or liver tissue
in vitro then using liver tissue concentrations makes more sense. If,
however, the Vm/Km values are estimated from plasma or blood
concentration time data then using blood concentrations may be more
appropriate. - db]
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)