Pool, F;
Sweby, PK;
Tindall, MJ;
(2018)
An Integrated Mathematical Model of Cellular Cholesterol Biosynthesis and Lipoprotein Metabolism.
Processes
, 6
(8)
, Article 134. 10.3390/pr6080134.
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Abstract
Cholesterol regulation is an important aspect of human health. In this work we bring together and extend two recent mathematical models describing cholesterol biosynthesis and lipoprotein endocytosis to create an integrated model of lipoprotein metabolism in the context of a single hepatocyte. The integrated model includes a description of low density lipoprotein (LDL) receptor and cholesterol synthesis, delipidation of very low density lipoproteins (VLDLs) to LDLs and subsequent lipoprotein endocytosis. Model analysis shows that cholesterol biosynthesis produces the majority of intracellular cholesterol. The availability of free receptors does not greatly effect the concentration of intracellular cholesterol, but has a detrimental effect on extracellular VLDL and LDL levels. We test our model by considering its ability to reproduce the known biology of Familial Hypercholesterolaemia and statin therapy. In each case the model reproduces the known biological behaviour. Quantitative differences in response to statin therapy are discussed in the context of the need to extend the work to a more in vivo setting via the incorporation of more dietary lipoprotein related processes and the need for further testing and parameterisation of in silico models of lipoprotein metabolism.
| Type: | Article |
|---|---|
| Title: | An Integrated Mathematical Model of Cellular Cholesterol Biosynthesis and Lipoprotein Metabolism |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3390/pr6080134 |
| Publisher version: | http://dx.doi.org/10.3390/pr6080134 |
| Language: | English |
| Additional information: | This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0). |
| Keywords: | Science & Technology, Technology, Engineering, Chemical, Engineering, ordinary differential equation, SREBP-2, RECEPTOR-MEDIATED ENDOCYTOSIS, COENZYME-A REDUCTASE, HMG-COA REDUCTASE, LDL-RECEPTOR, FAMILIAL HYPERCHOLESTEROLEMIA, HUMAN FIBROBLASTS, MESSENGER-RNA, HEPG2 CELLS, HUMAN-LIVER, PATHWAY |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10057117 |
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