PubMed Health⌕ Search

Biomedical subjects

R A Majewski

Publications and source records attributed to R A Majewski.

2 recordsLinked to original sources

Determining pathway structure-property relationships through experimentation and analytical frameworks.

A brief description of the information content of the experimental methods that are becoming increasingly useful for probing intracellular processes, a framework for interpreting observations, and an example that combines framework results and 13C NMR observations have been presented. Results in terms of structural criterion have been obtained that suggest that it may be possible to develop a glossary of structure-function heuristics. From the engineering point of view, such general work may also provide keys to system/subsystem modeling due to having some classic and nonclassic network properties mapped in advance. However, we note that approaches based solely on kinetics ignore physiochemical processes. A number of potential processes were mentioned earlier. Investigations of the importance of such processes, though, have been limited due to the dominance of in vitro enzyme kinetic and regulation work. Nonetheless, interesting proposals have been advanced by a limited number of workers, such as the suggestion that membrane-bound and soluble populations of enzymes with high and low activity, respectively, exist in eukaryotes (e.g., aldolase22) and the balanced attained between the two populations is an important regulatory mechanism. In an effort to contribute to the evaluation of physiochemical processes, our formalism was recently used to explore the logic of enzyme turnover number-enzyme amount distributions from the standpoint of minimizing excess enzymatic capacity (i.e., minimizing excess energy expenditure for protein biosynthesis) and the use of limited cytoplasmic solvation capacity (i.e., concentrated cytoplasm is water-limited; hence, maintaining the solubility of all constituents is difficult).

Biochemistry↗

Consideration of the gain, enzymatic capacity utilization, and response time properties of metabolic networks as a function of operating point and structure.

Computer simulation is used to examine the gain, utilization of enzymatic capacity and response time properties of a simple metabolic network consisting of a sequence of irreversible enzyme reactions controlled by non-allosteric feedback inhibition. The latter properties are chosen because interpretation of a metabolic network's structure can be aided by envisioning the network to maximize a single objective such as flux control. However, by examining the properties as a function of the network's operating point (extent of saturation of the first enzymatic reaction) and structural characteristics, it is found that apparent trade-offs occur between definable objectives. It is suggested that greater consideration of the trade-offs that may occur could help generate metabolic network heuristics and facilitate the interpretation of metabolic networks in terms of the functional role they play in the intact organism.

Computers↗