Michaelis-Menten model exceptions

If the concentrations of the products P and Q in the models summarized in Table 7-1 are set to zero, the resulting rate equations will be identical to Eq. (44) in all cases with the exception of the ping-pong mechanism. This means that the Michaelis-Menten double substrate kinetics is valid under the above circumstances. 

Kinetic templates accelerate reaction of bound substrates, which makes it tempting to quantify template effects in terms of rate enhancement . In this section, we will show how this can be misleading because such rate enhancements are concentration dependent. We will elucidate the parameters which determine the rate enhancement achieved with a kinetic template, by analyzing the thermodynamic and kinetic behavior of simple theoretical models, and applying these models to published template systems. Our theoretical models are similar to the Michaelis-Menten analysis of enzyme catalyzed reactions [51], except that we assume there is no catalytic turnover. First, we consider linear templates, then cyclization templates. In general, the rate of reaction varies as the reaction proceeds whenever we refer to rates in the following discussion, we mean initial rates. 

Pharmacokinetic models describe the biological processes of absorption, distribution, metabolism, and excretion of exogenous compounds. With the exception of absorption into and across the skin, absorption, distribution, metabolism, and elimination are essential processes that also occur with nutrients and endogenous compounds. Many of these processes can become nonlinear with increasingly higher exposure concentrations. Pulmonary absorption can be limited by respiratory rates. Metabolism can often show Michaelis-Menten or saturable kinetics. Distribution can be limited by the affinity of the chemical for a specific tissue or by blood flow. 

The PBPK-PD model presented here is based on previously developed PBPK-PD models describing the kinetics and dynamics resulting from DFP or GB exposure, and has diffusion limited compartments for the brain, diaphragm, fat, kidneys, liver, lungs, skin, and the remaining rapidly and slowly perfused tissues (Figures 8.1 and 8.2). The model includes B-esterase (AChE, BuChE and CaE) activity (Figure 8.3) in all tissues except fat metabolism of VX v/fl Michaelis-Menten kinetics in the blood, brain, kidneys, liver and rapidly perfused compartment and first-order urinary excretion from... 

---