User:Johnsy/Lipoprotein Modelling/Model Development: Difference between revisions
(New page: ==HMG-CoA Reductase and Cholesterol== Cholesterol Producers (Sources) *''de novo'' - Acetyl CoA via HMG CoA and enzyme HMG CoA reductase *IDL particles accepted into the cell via LDL rece...) |
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To simplify the model, we can simply say that both the concentration of cholesterol and statins will negatively affect the rate of the enzyme HMG CoA reductase and will limit the production of mevalonate (another key intermediary in cholesterol biosynthesis). | To simplify the model, we can simply say that both the concentration of cholesterol and statins will negatively affect the rate of the enzyme HMG CoA reductase and will limit the production of mevalonate (another key intermediary in cholesterol biosynthesis). | ||
==Adjusting the Model Developed by Barahona, et al.== | |||
If we have a look again at the equation which governed the intracellular concentration of cholesterol, we see that we must target this equation if we want to take into account the ''de novo'' pathway for cholesterol biosynthesis. | |||
<center><math> | |||
\frac{d[IC]}{dt} = (\chi_{I}d_{I}[IDL] + \chi_{L}d_{L}[LDL])\phi_{LR} + \chi_{L}d[LDL] - d_{IC}[IC] | |||
</math></center> | |||
From the biology, we know that the 'de novo' pathway will be a source of intracellular cholesterol that is dependent upon the concentration of cholesterol there is in the cell. Thus, we obtain the straightforward addition below, where ''n'' denotes the rate constant for the biosynthesis of cholesterol determined by the maximum rate of HMG-CoA reductase, the limiting step in the biosynthesis pathway. | |||
<center><math> | |||
\frac{d[IC]}{dt} = n[IC] + (\chi_{I}d_{I}[IDL] + \chi_{L}d_{L}[LDL])\phi_{LR} + \chi_{L}d[LDL] - d_{IC}[IC] | |||
</math></center> | |||
Revision as of 10:02, 31 October 2007
HMG-CoA Reductase and Cholesterol
Cholesterol Producers (Sources)
- de novo - Acetyl CoA via HMG CoA and enzyme HMG CoA reductase
- IDL particles accepted into the cell via LDL receptors
- LDL particles accepted into the cell via LDL receptors
Cholesterol Fates (Sinks)
- Bile acids via enzyme cholesterol 7-α-hydroxylase
de novo Pathway
HMG CoA reductase is the rate limiting enzyme in the biosynthesis of cholesterol. Its transcription is upregulated by the sterol regulatory element binding protein (SREBP) which binds to the streol regulatory element (SRE) to transcribe the gene for HMG CoA reductase. SREBP is usually situated on the membrane of the endoplasmic reticulum or the nuclear membrane, but when bound by cholesterol, the protein is released via proteolysis and migrates to the nucleus where it binds to the SRE to initiate transcription.
Statins limit the action of HMG CoA reductase by acting as a competitive inhibitor since it resembles the HMG CoA molecule.
To simplify the model, we can simply say that both the concentration of cholesterol and statins will negatively affect the rate of the enzyme HMG CoA reductase and will limit the production of mevalonate (another key intermediary in cholesterol biosynthesis).
Adjusting the Model Developed by Barahona, et al.
If we have a look again at the equation which governed the intracellular concentration of cholesterol, we see that we must target this equation if we want to take into account the de novo pathway for cholesterol biosynthesis.
From the biology, we know that the 'de novo' pathway will be a source of intracellular cholesterol that is dependent upon the concentration of cholesterol there is in the cell. Thus, we obtain the straightforward addition below, where n denotes the rate constant for the biosynthesis of cholesterol determined by the maximum rate of HMG-CoA reductase, the limiting step in the biosynthesis pathway.
