Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cholesterol molecule is at the center of the pathophysiology of many vascular diseases. Whole-body cholesterol pools are maintained by a balance of endogenous synthesis, dietary absorption and elimination from our bodies. While the cellular aspects of cholesterol metabolism received significant impetus from the seminal work of Goldstein and Brown investigating LDL receptor trafficking, how dietary cholesterol was absorbed and eliminated was relatively neglected. The identification of the molecular defect a rare human disorder, Sitosterolemia, led to elucidation of a key mechanism of how we regulate the excretory pathway in the liver and in the intestine. Two proteins, ABCG5 and ABCG8, constitute a heterodimeric transporter that facilitates the extrusion of sterols from the cell into the biliary lumen, with a preference for xenosterols. This mechanism explained how dietary xenosterols are prevented from accumulating in our bodies. In addition, this disease has also highlighted the potential harm of xenosterols; macrothrombocytopenia, liver disease and endocrine disruption are seen when xenosterols accumulate. Mouse models of this disease suggest that there are more dramatic alterations of physiology, suggesting that these highly conserved mechanisms have evolved to prevent these xenosterols from accumulating in our bodies.
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PMID:Investigating Sitosterolemia to Understand Lipid Physiology. 2992 17