2016 Conference on Computational Modelling with COPASI
Manchester Institute of Biotechnology, 12th – 13th May, 2016
1 - University of Chester, UK; 2 - Liverpool Hope University, UK
Keywords: Folate Cycle, Ageing, DNA Methylation, Microbial Computational Model
Dietary folates (Vitamin B9) have a key role to play in health as deficiencies in the intake of these B vitamins have been implicated in a wide variety of clinical conditions. Folates function as single carbon donors in the synthesis of methionine and nucleotides. Moreover, folates have a vital role to play in the epigenetics of mammalian cells by supplying methyl groups for DNA methylation . In mammalian cells folate metabolism is characterised by the complex biochemical reactions of the folate cycle. Microbial folate metabolism differs from its mammalian counterpart, as microbes have retained a biosynthetic pathway within the intracellular folate cycle. This pathway acts like a switch when environmental folate levels are low. To deal with the inherent complexity associated with both biochemical systems we are using computational modelling . Our microbial kinetic model is the first of this system. We have used the model to help identify potential novel antifolates. Moreover, our COPASI formulated model supports the hypothesis that a folinic acid biosynthesis loop acts as a folate-mediated regulatory circuit in cell growth . Our mammalian computational model of folate metabolism integrates with the biochemical reactions which underpin the DNA methylation cycle. Our biological rationale for doing this is unpinned by the knowledge that perturbations to the folate cycle are strongly coupled with age associated aberrant DNA methylation . This suggests a deeper mechanistic understanding of the interaction between the folate cycle and DNA methylation could be pivotal in improving our understanding of ageing.