Cholesterol disposal via hydroxylation is an important way to maintain cholester

Question

Cholesterol disposal via hydroxylation is an important way to maintain cholesterol homeostasis. One protein that plays a critical role in this process is a cytochrome P-450 enzyme known as CYP27A1. This protein catalyzes the hydroxylation of cholesterol to form 27-hydroxycholesterol (an oxysterol). This oxysterol serves as a ligand for the Liver X Receptor (LXR, a nuclear hormone receptor). LXR functions (in cooperation with the Retinoid X Receptor, RXR, by forming an LXR:RXR heterodimer) to increase the transcription of genes involved in maintaining cholesterol homeostasis. For each of the LXR targets listed below, describe the role of each in cholesterol metabolism (you may find it useful to talk about a particular tissue or cell-type, e.g., CYP7A1 in the liver).

a. ABCA1

b. CYP7A1

c. ApoE

d. LPL

e. SR-B1

Explanation / Answer

ABCA 1 and Apo E are the genes/gene products involved in efflux of cholesterol when intracellular cholesterol concentration increases.

CYP7A1 = enzyme involved in bile acid formation, its a rate limiting enzyme.

LPL = lipo protein lipases; enzymes which form fatty acids from VLDL.

Apo E = Regrowth of axon, anti-oxidant, anti-inflammatory roles, anti- excito- toxicity roles.

SRE-BP1 = transcription factor plays role in cholesterol uptake, lipid metabolism, regulating lipogenesis.

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