Recent discoveries concerning regulation of Cholesterol Biosynthesis and Sterol Regulated Element Binding Proteins (SREBPs) in the liver.

Riemsma, M (2018) Recent discoveries concerning regulation of Cholesterol Biosynthesis and Sterol Regulated Element Binding Proteins (SREBPs) in the liver. Bachelor's Thesis, Biology.

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Abstract

Cholesterol is an important component of cellular membranes and plays an important role in several physiological processes. Atypical accumulation of cholesterol in the blood elevates the risk of cardiovascular disease, so its homeostasis has to be tightly regulated. Cholesterol is synthesized (de novo) via the mevalonate pathway, and the clearance of plasma cholesterol is highly dependent on the expression of LDL-receptors in the liver. Cellular cholesterol levels are tightly controlled by a family of membrane-bound transcription factors: Sterol-Regulatory Element-Binding Proteins (SREBPs). SREBP isoforms SREBP-2 and SREBP-1c bind to the DNA of promotor/enhancer regions of genes involved in cholesterol- and lipid synthesis, respectively. SREBPs transcription factor activity is regulated by SREBP processing, which produces nuclear SREBP (nSREBPs). nSREBPs regulate transcription of SREBPs themselves, by binding to the promotor/enhancer region in the Srebf2 and Srebf1 genes. Transcription of Srebf1 is also dependent on activation of the Liver-X-Receptor (LXR). Cholesterol levels are also regulated by controlling the flux over the mevalonate pathway, via degradation of 3-hydroxy-3-methylglutaryl-CoA Reductase (HMGCR). There are still a lot of questions surrounding the regulation of SREBPs and cholesterol. More research has to be done to fully understand the mechanisms involved. Said mechanisms might eventually be manipulated for pharmaceutical purposes, which could aid in the treatment against cardiovascular diseases. This paper focused on methods of cholesterol regulation in the liver that were recently discovered.

Item Type:	Thesis (Bachelor's Thesis)
Degree programme:	Biology
Thesis type:	Bachelor's Thesis
Language:	English
Date Deposited:	15 Feb 2018 08:35
Last Modified:	15 Feb 2018 08:35
URI:	https://fse.studenttheses.ub.rug.nl/id/eprint/16411

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