/pdf/convex-analysisnoer-san-nojin-zhan-nituite-5dl2rbmoyr.pdf

Convex Analysisの二,三の進展について

Metabolites are the end products of cellular regulatory processes, and their levels can be regarded as the ultimate response of biological systems to genetic or environmental changes. In parallel to the terms ‘transcriptome’ and ‘proteome’, the set of metabolites synthesized by a biological system constitute its ‘metabolome’. Yet, unlike other functional genomics approaches, the unbiased simultaneous identification and quantification of plant metabolomes has been largely neglected. Until recently, most analyses were restricted to profiling selected classes of compounds, or to fingerprinting metabolic changes without sufficient analytical resolution to determine metabolite levels and identities individually. As a prerequisite for metabolomic analysis, careful consideration of the methods employed for tissue extraction, sample preparation, data acquisition, and data mining must be taken. In this review, the differences among metabolite target analysis, metabolite profiling, and metabolic fingerprinting are clarified, and terms are defined. Current approaches are examined, and potential applications are summarized with a special emphasis on data mining and mathematical modelling of metabolism.

https://link.springer.com/content/pdf/10.1023%2FA%3A1013713905833.pdf

Metabolomics - the link between genotypes and phenotypes

Motivation: Simulation and modeling is becoming a standard approach to understand complex biochemical processes. Therefore, there is a big need for software tools that allow access to diverse simulation and modeling methods as well as support for the usage of these methods.

Results: Here, we present COPASI, a platform-independent and user-friendly biochemical simulator that offers several unique features. We discuss numerical issues with these features; in particular, the criteria to switch between stochastic and deterministic simulation methods, hybrid deterministic--stochastic methods, and the importance of random number generator numerical resolution in stochastic simulation.

Availability: The complete software is available in binary (executable) for MS Windows, OS X, Linux (Intel) and Sun Solaris (SPARC), as well as the full source code under an open source license from http://www.copasi.org.

Contact: mendes@vbi.vt.edu

/pdf/copasi-a-complex-pathway-simulator-320i5gmr5f.pdf

COPASI---a COmplex PAthway SImulator

Directed movement is a characteristic of many living organisms and occurs as a result of the transformation of chemical energy into mechanical energy. Myosin is one of three families of molecular motors that are responsible for cellular motility. The three-dimensional structure of the head portion of myosin, or subfragment-1, which contains both the actin and nucleotide binding sites, is described. This structure of a molecular motor was determined by single crystal x-ray diffraction. The data provide a structural framework for understanding the molecular basis of motility.

https://science.sciencemag.org/content/sci/261/5117/50.full.pdf

Three-dimensional structure of myosin subfragment-1: a molecular motor

On Educational psychology: A cognitive view.

Motivation: To reconstruct metabolic pathways from biochemical and/or genome sequence data, the stoichiometric and thermodynamic feasibility of the pathways has to be tested. This is achieved by characterizing the admissible region of flux distributions in steady state. This region is spanned by what can be called a convex basis. The concept of 'elementary flux modes' provides a mathematical tool to define all metabolic routes that are feasible in a given metabolic network. In addition, we define 'enzyme subsets' to be groups of enzymes that operate together in fixed flux proportions in all steady states of the system. Results: Algorithms for computing the convex basis and elementary modes developed earlier are briefly reviewed. A newly developed algorithm for detecting all enzyme subsets in a given network is presented. All of these algorithms have been implemented in a novel computer program named METATOOL, whose features are outlined here. The algorithms are illustrated by an example taken from sugar metabolism. Availability: METATOOL is available from ftp://bmsdarwin.brookes.ac.uk/pub/software/ibmpc/metatool. Supplementary information: http://www.biologie.hu-berlin.de/biophysics/Theory/tpfeiffer/metatool.html.

/pdf/metatool-for-studying-metabolic-networks-3m0vafezga.pdf

METATOOL: for studying metabolic networks.

The efficiency of photosensitized DNA cleavage and quantum yields of singlet oxygen production (ΦΔ) have been determined for the metal complexes [Ru(bpy)2(ddz)]2+, [Ru(phen)2(ddz)]2+, [Ru(phen)3]2+, and [Ru(dsdp)3]4- (bpy = 2,2‘-bipyridine, ddz = dibenzo[h,j]dipyrido[3,2-a:2‘,3‘-c]phenazine, phen = 1,10-phenanthroline, and dsdp = 1,10-phenanthroline-4,7-diphenylsulfonate). ΦΔ values (0.19−0.52) have been measured in O2-saturated D2O solution, both in the absence and presence of DNA. Protection of the photoexcited Ru(II) complexes from O2 quenching imparted by the polynucleotide was evaluated from their emission lifetimes (0.13−3.7 μs) measured at three different O2 concentrations. Our results show the highest photocleavage efficiency for those sensitizers that display strong affinity for DNA (binding constant Kb > 106 M-1), despite their lower ΦΔ values (0.08−0.10 for the three cationic complexes vs 0.40 for the tris-dsdp, in H2O/air/DNA). Kinetic analysis (agarose gel electrophoresis) of the photocleavag...

Singlet Oxygen-Mediated DNA Photocleavage with Ru(II) Polypyridyl Complexes

It is analyzed whether the structural design of contemporary glycolysis can be explained theoretically on the basis of optimization principles originating from natural selection during evolution. Particular attention is paid to the problem of how the kinetic and thermodynamic properties of the glycolytic pathway are related to its stoichiometry with respect to the number and location of ATP-coupling sites. The mathematical analysis of a minimal model of unbranched energy-converting pathways shows that the requirement of high ATP-production rate favours a structural design that includes not only ATP-producing reactions (P-sites) but also ATP-consuming reactions (C-sites). It is demonstrated that, at fixed overall thermodynamic properties of a chain, the ATP-production rate may be enhanced by kinetic optimization. The ATP-production rate is increased if the C-sites are concentrated at the beginning and all the P-sites at the end of the pathway. An optimum is attained, which is characterized by numbers of coupling sites corresponding to those found in glycolysis. Various extensions of the minimal model are considered, which allow the effects of internal feedback-regulations, variable enzyme concentrations, and the symmetric branching of glycolysis at the aldolase step to be considered.

/pdf/theoretical-approaches-to-the-evolutionary-optimization-of-5r39bwlrdp.pdf

Theoretical approaches to the evolutionary optimization of glycolysis Thermodynamic and kinetic constraints

In the first past of this work [Heinrich, R., Montero, F., Klipp, E., Waddell, T.G. and Melendez-Hevia, E. (1997) Eur. J. Biochem. 243, 191-201] the kinetic and thermodynamic constraints under which an optimal glycolysis must be designed have been analysed. In this second part, we present a chemical analysis of the glycolytic pathway in order to determine if its design is chemically optimized according the possibilities that a glycolytic design can have. Our results demonstrate that glycolysis in modern-day cells (from glucose to lactate) has an optimized design for maximizing the flux of ATP production, and a thermodynamic profile which guarantees a high kinetic efficiency. We also discuss some cases of paleometabolism for this pathway as alternative metabolic pathways, less optimized, that exist in some bacteria. Our analysis relates mainly to metabolism designed under constant chemical affinity (substrates and products of the pathway constant), where the target of optimization can be the flux of ATP production. We also discuss the case of an externally imposed input flux, whose target of optimization is the stoichiometric yield of ATP.

/pdf/theoretical-approaches-to-the-evolutionary-optimization-of-2qfju82woc.pdf

Francisco Montero

Papers

METATOOL: for studying metabolic networks.

Singlet Oxygen-Mediated DNA Photocleavage with Ru(II) Polypyridyl Complexes

Theoretical approaches to the evolutionary optimization of glycolysis Thermodynamic and kinetic constraints

Theoretical approaches to the evolutionary optimization of glycolysis--chemical analysis.

Optimization of Metabolism: The Evolution of Metabolic Pathways Toward Simplicity Through the Game of the Pentose Phosphate Cycle