Stability mechanisms, metabolic modeling

Chapter 16 applies thermodynamics to problems of biological interest. The metabolic processes leading to mechanical work performed by a living organism are described first, followed by discussions of the role of thermodynamics as a tool for understanding the stabilities of biopolymers such as proteins, and oligonucleotides as model compounds for DNA. 

Lewin JL, Cramer CJ. Rapid quantum mechanical models for the computational estimation of C-H bond dissociation energies as a measure of metabolic stability. Mol Pharm 2004 1 128-35. 

Oxidative Biotransformation in Microsomes The rapid determination of pharmacokinetic parameters, solubility, permeability, and in vitro stability in plasma or liver tissue can often provide a reasonable explanation of the mechanisms limiting oral bioavailability. An approach that is often used is to extrapolate the in vitro rate of metabolism to estimate the hepatic clearance using in vitro-in vivo correlation methods.82-86 These methods use in vitro kinetic parameters, usually Vmllx/Km or in vitro t ji, to determine the intrinsic clearance, which is then scaled to hepatic clearance using the amount of tissue in the in vitro incubation, the weight of the liver, and the well-stirred model for hepatic clearance. 

---