Metabolically structured model

Metabolically Structured Models Stimulated by Dynamically Changing Environment - Integration of CFD and Structured Kinetic Models... 

Models for batch culture can be constructed by assuming mechanisms for each phase of the cycle. These mechanisms must be reasonably comph-cated to account for a lag phase and for a prolonged stationary phase. Unstructured models treat the cells as a chemical entity that reacts with its environment. Structured models include some representation of the internal cell chemistry. Metabolic models focus on the energy-producing mechanisms within the cells. 

Balakin KV, Ekins S, Bugrim A, Ivanenkov YA, Korolev D, Nikolsky Y, et al. Quantitative structure-metabolism relationship modeling of the metabolic V-dealkylation rates. Drug Metab Dispos 2004 32 1111-20. 

The virtual compounds can be screened against structural models of the metabolizing enzymes, including the known SNP variants. These procedures are becoming widely adopted for the cytochrome P450 isozymes involved in oxidative drug metabolism. 

Long, A. and J. D. Walker. 2003. Quantitative structure-activity relationships for predicting metabolism and modeling cytochrome p450 enzyme activitiEsiviron. Toxicol. Cherr22 1894-1899. 

One of the pioneers of structured models in animal cell culture used a single-cell model (Batt and Kompala, 1989). Based on hybridoma metabolism (.Figure 8.6), the model was based on the formulation of four compartments amino acids (including the TCA precursors), the nucleotides (including DNA and RNA), the proteins, and lipids. The excreted byproducts (lactate and ammonia) and the excreted product (mAb) were also considered. However, although flexible for simulation of different... 

Structural models of protein and nucleic acid molecules derived by X-ray crystallography are exttemely interesting in themselves, each being a representative member of some architectural class of macromolecule shaped by evolutionary time and process toward the optimal completion of a specific cellular or metabolic task. They are nevertheless static objects. Because the catalytic functions they perform depend on dynamic events involving the interaction of the macromolecules with substrates, effectors, inhibitors, and other cellular components, we are constantly searching for techniques that will allow us to visualize the macromolecules in some intermediate stages of a biochemical or physiological activity. 

Another two key concepts in metabolic engineering are metabolic pathway analysis and metabolic pathway modeling. The former is used for assessing inherent network properties in the complete biochemical reaction networks. It involves identification of the metabolic network structure (or pathway topology), quantification of the fluxes through the branches of the metabolic network, and identification of the control structures within the metabolic network. 

The paradigm for both modular PKSs and NRPSs is that each module incorporates one building block into the natural product (Figures 1 and 2). Within each module there are different domains and each domain catalyzes a specific reaction in the assembly of the metabolic product. Model examples of this colinearity between module and domain organization and metabolite structure for type I modular PKS and NRPS systems are respectively represented by erythromycin and tyrocidine biosyntheses. This colinearity is an important feature that underpins our ability to predict structural features of the metabolic products of novel modular PKS and NRPS systems discovered by genomics. 

The basic structural model of flavanones is the 2-phenylbenzopiran-4-one skeleton [6], The flavanones are compounds of great interest due to the fact that they are a compulsory step in the metabolic pathway of the other flavonoids. Their metabolic precursors are the chalcones, and the flavones, the dihydroflavonols, and the isoflavones are biosynthesised from the flavanones. 

Rotboll, M., Jorgensen, S. B. (1993). Validation of a metabolic and biomass structured model for yeast fermentation. In European Conference on Biotechnology, Florence, Italy. 

The kinetics of soluble and immobilized enzymes. Involved In reactions of soluble and Insoluble substrates appears to be sufficiently well studied over the last 20 years that reactor design procedures based on fundamental kinetics rate equations may be executed with considerable confidence. The application of such emzyme kinetics forms to structured models of microbial metabolism has also progressed, as this book documents. 

---