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A model of flux regulation in the cholesterol biosynthesis pathway: Immune mediated graduated flux reduction versus statin-like led stepped flux reduction.

Watterson S, Guerriero ML, Blanc M, Mazein A, Loewe L, Robertson KA, Gibbs H, Shui G, Wenk MR, Hillston J, Ghazal P - Biochimie (2012)

Bottom Line: Using data taken from primary bone marrow derived macrophage cells infected with murine cytomegalovirus or treated with IFNγ, we show that, under these assumptions, coordinate down-regulation of enzyme activity imparts a graduated reduction in flux along the pathway.The graduated reduction mediated by physiological coordinate regulation of multiple enzymes supports a mechanism that allows a greater level of specificity, altering cholesterol levels with less impact upon interactions branching from the pathway, than pharmacological step reductions.We argue that coordinate regulation is likely to show a long-term evolutionary advantage over single enzyme regulation.

View Article: PubMed Central - PubMed

Affiliation: Division of Pathway Medicine, University of Edinburgh Medical School, Chancellor's Building, 49 Little France Crescent, Edinburgh, Scotland, United Kingdom. s.watterson@ed.ac.uk

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A model of flux regulation in the cholesterol biosynthesis pathway: Immune mediated graduated flux reduction versus statin-like led stepped flux reduction.

Watterson S, Guerriero ML, Blanc M, Mazein A, Loewe L, Robertson KA, Gibbs H, Shui G, Wenk MR, Hillston J, Ghazal P - Biochimie (2012)

© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3585962&req=5

Bottom Line: Using data taken from primary bone marrow derived macrophage cells infected with murine cytomegalovirus or treated with IFNγ, we show that, under these assumptions, coordinate down-regulation of enzyme activity imparts a graduated reduction in flux along the pathway.The graduated reduction mediated by physiological coordinate regulation of multiple enzymes supports a mechanism that allows a greater level of specificity, altering cholesterol levels with less impact upon interactions branching from the pathway, than pharmacological step reductions.We argue that coordinate regulation is likely to show a long-term evolutionary advantage over single enzyme regulation.

View Article: PubMed Central - PubMed

Affiliation: Division of Pathway Medicine, University of Edinburgh Medical School, Chancellor's Building, 49 Little France Crescent, Edinburgh, Scotland, United Kingdom. s.watterson@ed.ac.uk

Show MeSH
Related in: MedlinePlus