Physiology, question compartmentation

Biosynthesis of IAA from tryptophan uses the L-form of the amino acid.75 Some of the enzymes that catalyze the conversion of specific intermediates have been identified, and some of the genes coding for the enzymes have been cloned. Such findings establish that plants are competent to carry out such metabolic conversions however, the specific involvement of these genes and intermediates requires confirmation, because biochemical studies carried out with applications to tissue segments or with extracts could disrupt tissue and cellular compartmentalization and because enzymes that catalyze the conversion of tryptophan to IAA in vitro may never come into contact with the intermediates in vivo. Thus, the physiological relevance of some of these pathways remains an open question.69 An additional concern is that many of the enzymes have wide substrate specificities, so it has been difficult to implicate them solely in IAA biosynthesis. Some of the intermediates and enzymes that have been described to have the competence to carry out these reactions are discussed below. 

More sophisticated approaches to predict the extent of oral absorption of drugs use mathematical models based on the known physiology and utilizing simple physicochemical measurements as input. The GastroPlus [4] program is a commercial tool that utilizes an advanced compartmental and transit model, based on the work of Amidon and Yu [5], and allows what-if questions to be posed to enable pharmaceutical optimization (see Chapter 17). For instance, the impact of morphology, formulation, and/or particle size changes, and sensitivity analysis to include errors in parameters on the prediction, can be considered. 

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