In class we talked about the formation of VLDL lipoproteins in the liver. The as
ID: 177597 • Letter: I
Question
In class we talked about the formation of VLDL lipoproteins in the liver. The assembly of VLDL particles within the liver involves a protein called microsomal triglyceride transfer protein (MTP), which is essential for the assembly of apolipoprotein B (apo-B) containing lipoproteins. Known inhibition of MTP prevents hepatic VLDL secretion by preventing VLDL production. Given this effect, drugs targeting MTP are of interest as potential drugs for hyperlipidemia (a condition with elevated levels of lipid and/or lipoproteins).
As with any drug, there are associated side effects. The side effects of MTP inhibition include a condition called steatorrhea, which is the excretion of abnormal quantities of fat in the feces. Please explain this side effect, including any relevant pathways and/or lipoproteins involved.
Explanation / Answer
The side effects of MTP inhibition include a condition called steatorrhea. By inhibiting microsomal triglyceride transfer protein (MTP), lipids and triglycerides are stopped from moving around the body thereby accumulating in cells. The accumulation of lipids in abnormal levels in the cell is known as Steatosis and excretion of these accumulated lipids is steatorrhea. There is no single mechanism for the accumulation of lipids and triglycerides since disruption of lipid movement can come from many routes. But broadly it is of 2 types. 1. accumulation due to the failure of lipid breakdown and 2. excessive lipid production or intake, than can be absorbed.
MTP not only translocates apolipoprotein, but also translocates esterified cholesterol and triglycerides across membranes and assemble them with the apolipoprotein. This assembly creates VLDL which can then be taken to different parts of the body. VLDL maintains a low steady state amount of triglycerides by absorption of non-esterified fatty acids by de novo lipogenesis and disposing triglycerides for fatty acid oxidation. Thus blocking VLDL formation, accumulation of fats and excretion in stool comes as a side effect.
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