Regulation of HMGCR in the mevalonte pathway

The importance of cholesterol in health and disease is commonly understood since many studies have correlated increase detection of cholesterol in blood with many diseases such as cardiovascular disease or elevated blood pressure. In this study we investigate the activation/inactivation mechanism of cholesterol synthesis in response to AMP/ATP ratio. The link step between energy need and inactivation of cholesterol synthesis is mediated by AMP activated protein kinase (AMPK) through phosphorylation of 3- hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), the enzyme catalysing the committing step in cholesterol synthesis.Besides the fact that this system is known for years and is one of the first AMPK regulated pathways identified, the full pathway involved in this regulation has not been caught clearly in literature. There are numerous studies referring to AMPK regulated pathways but not a concrete piece of work combining the newly retrieved knowledge on AMPK regulation as well as the antagonized effects of HMGCR dephosphorylation. In order to produce a clear and easily understood description of the pathway we decided to create a map depiction of the system. After careful manual curation of the relative papers and taking advantage of the SBGN notation, a community driven system notation with computational potentials, we constructed a map depicting the well characterized interactions of proteins involved in this system, particular in human organism. The aim of this project is the collection of the available information, characterization of the relation between pathway players and the production of a map that would be a helpful tool in identifying potential drug targets and generally improve the understanding of the regulation mechanism.