Biomedical subjects

M L Mavrovouniotis

Publications and source records attributed to M L Mavrovouniotis.

8 recordsLinked to original sources

PubMed1997

Estimation of equilibrium constants using automated group contribution methods.

MOTIVATION: Group contribution methods are frequently used for estimating physical properties of compounds from their molecular structures. An algorithm for estimating Gibbs energies of formation through group contribution methods has been automated in an object-oriented framework. The algorithm decomposes compound structures according to a basis set of groups. It permits the use of wildcards and is able to distinguish between ring groups and chain groups that use similar search structures. Past methods relied on manual decomposition of compounds into constituent groups. RESULTS: The software is written in Common LISP and requires < 2 min to estimate Gibbs energies of formation for a database of 780 species of varying size and complexity. The software allows rapid expansion to incorporate different basis sets and to estimate a variety of other physical properties.

Algorithms↗

PubMed1996

Qualitative analysis of biochemical reaction systems.

The qualitative analysis of biochemical reaction systems is presented. A discrete event systems approach is used to represent and analyze bioreaction pathways. The approach is based on Petri nets, which are particularly suited to modeling stoichiometric transformations, i.e. the inter-conversion of metabolites in fixed proportions. The properties and methods for the analysis of Petri nets, along with their interpretation for biochemical systems, are presented. As an example, the combined glycolytic and pentose phosphate pathway of the erythrocyte cell is presented to illustrate the concepts of the methodology.

Animals↗

PubMed1994

Describing multiple levels of abstraction in the metabolism.

We discuss some central issues that arise in the computer representation of the metabolism and its subsystems. We provide a framework for the representation of metabolites and bioreactions at multiple levels of detail. The framework is based on defining an explicit linear mapping of metabolites and reactions from one level of detail to another. A simple reaction mechanism serves as an illustration and shows the emergence of the concept of a catalyst from metabolic abstraction levels.

Catalysis↗

PubMed1993

Identification of localized and distributed bottlenecks in metabolic pathways.

The usual thermodynamic evaluation, based solely on the Standard Gibbs Energy of reaction, does not take into account the permissible ranges of concentrations of metabolites, and it faces further difficulties when, instead of isolated reactions, we are examining whole pathways. For pathways, we seek not only to decide whether they are feasible but also to pinpoint the pathway segment that causes any thermodynamic difficulties. We define a set of scaled quantities which reformulate the thermodynamic-feasibility problem for the whole pathway. We present an algorithm which analyzes individual reactions and selective construction of larger subpathways and uncovers localized and distributed thermodynamic bottlenecks of the biotransformation. This type of thermodynamic treatment contributes to the effort to include more physical, chemical, and biological factors in the computer-aided analysis of metabolic pathways.

Algorithms↗

PubMed1993

Petri net representations in metabolic pathways.

The present methods for representing metabolic pathways are limited in their ability to handle complex systems, incorporate new information, and to provide for drawing qualitative conclusions from the structure of pathways. The theory of Petri nets is introduced as a tool for computer-implementable representation of pathways. Petri nets have the potential to overcome the present limitations, and through a multitude of properties, enable the preliminary qualitative analysis of pathways.

Computer Simulation↗

PubMed1991

Estimation of standard Gibbs energy changes of biotransformations.

Contributions and corrections for the estimation of standard Gibbs energies are given. The group contribution method, applicable to both cyclic and acyclic compounds, permits the approximate estimation of the standard Gibbs energy of a biotransformation, given the stoichiometry and structures of the metabolites involved. Estimated standard Gibbs energies of formation for a number of acyclic biochemical compounds are provided.

Biotransformation↗

PubMedDate not supplied

Enzymatic reaction rate limits with constraints on equilibrium constants and experimental parameters.

A general methodology is presented for estimating maximum rates of enzymatic reactions based on general characteristics of enzymatic reaction mechanisms, kinetic limits and thermodynamics. The useful range of experimentally derived kinetic parameters can also be extended by the methodology. The methodology divides the reaction mechanism into physical and chemical steps. Maximum rates that comply with kinetic and thermodynamic constraints are calculated by setting the physical rate constants to their diffusion limits and optimising the chemical rate constants subject to constraints of the reaction mechanism and overall equilibrium constant. Rate estimates from this methodology can be subject to additional constraints from experimental data, and thus conform to the distinctive features of the enzymatic reaction. The methodology is demonstrated using a reversible enzymatic reaction model involving ordered binding of two reactants and ordered release of two products (bi-bi mechanism). Numerical results are shown for alcohol dehydrogenase (EC 1.1.1.1), which has a bi-bi mechanism. Pyrophosphatase (EC 3.6.1.1) with a uni-bi mechanism and triosephosphate isomerase (EC 5.3.1.1) with a uni-uni mechanism are also examined.

Enzymes↗

PubMedDate not supplied

Model reduction in the computational modeling of reaction systems.

The underlying assumption for most lumping techniques is that the reduced models must be valid for the entire composition space. This is a harsh requirement that often limits the models that are generated. The scheme that is presented here uses the inherent structure of reaction systems to divide the composition space into regions. Within each region, the order-of-magnitude relationships that exist between terms in the rate equations are used to systematically reduce the order and coupling of the model. The full system is then described through piecewise combination of these simpler, region-specific models. Although these reduced models are based on assumptions that make them invalid globally, they are accurate within the regions for which they have been crafted.

Algorithms↗