Here we develop the use of artificial neural networks for solving the inverse metabolic problem, in other words, given a set of steady-state metabolite levels and fluxes in a pathway of known structure to obtain the parameters of the system, in this case the enzymatic limiting rate and Michaelis constants. This requires two main procedures: first the development of a computer program with which...

even purified enzyme preparations are often heterogeneous. for example, preparations of aspartate aminotransferase or cytochrome oxidase can consist of several different forms of the enzyme.  for this reason we consider how different the kinetics of the reactions catalysed by a mixture of forms of an enzyme must be to provide some indication of the characteristics of the species present.  based...

In Escherichia coli, protein degradation in synthetic circuits is commonly achieved by the ssrA-tagged degradation system. In this work, we show that the degradation kinetics for the green fluorescent protein fused with the native ssrA tag in each cell exhibits the zeroth-order limit of the Michaelis-Menten kinetics, rather than the commonly assumed first-order. When measured in a population, t...

Basimglurant, a novel mGlu5-negative allosteric modulator under development for the treatment of major depressive disorder, is cleared via cytochrome P450 (P450)-mediated oxidative metabolism. Initial enzyme phenotyping studies indicated that CYP3A4/5 dominates basimglurant metabolism and highlights a risk for drug-drug interactions when it is comedicated with strong CYP3A4/5 inhibitors or inac...

8-Oxoguanine-DNA glycosylase 1 (OGG1), with intrinsic AP lyase activity, is the major enzyme for repairing 7,8-dihydro-8-oxoguanine (8-oxoG), a critical mutagenic DNA lesion induced by reactive oxygen species. Human OGG1 excised the damaged base from an 8-oxoG. C-containing duplex oligo with a very low apparent k(cat) of 0.1 min(-1) at 37 degrees C and cleaved abasic (AP) sites at half the rate...

In this paper we discuss the question of how to decide when a general chemical reaction system is incapable of admitting multiple equilibria, regardless of parameter values such as reaction rate constants, and regardless of the type of chemical kinetics, such as mass-action kinetics, Michaelis-Menten kinetics, etc. Our results relate previously described linear algebraic and graph-theoretic con...

CRISPR-diagnostic assays have gained significant interest in the last few years. This has grown rapidly during current COVID-19 pandemic, where CRISPR-diagnostics been frontline contenders for rapid testing solutions. surge research prompts following question: what exactly are achievable limits of detection and associated assay times enabled by kinetics enzymes such as Cas12 Cas13? To explore t...

Even purified enzyme preparations are often heterogeneous. For example, preparations of aspartate aminotransferase or cytochrome oxidase can consist of several different forms of the enzyme.  For this reason we consider how different the kinetics of the reactions catalysed by a mixture of forms of an enzyme must be to provide some indication of the characteristics of the species present.  Based...