In class we talked about the formation of VLDL lipoproteins in the liver. The as

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).

1a) Based on your understanding of relevant pathways involving VLDL, explain the basis of MTP inhibition as a hyperlipidemia drug. Would you expect LDL levels in the blood to increase or decrease?

Explanation / Answer

MTP is Microsomal triglyceride transfer protein which is an  endosomal protein is located in the hepatocytes and intestinal enterocytescatalyses. This protein catalyses the assembly of cholesterol, triglycerides, and apo B to VLDL, or chylomicrons. Microsomal triglyceride transfer protein Inhibitors (MTP-I) are cholesterol and triglyceride lowering agents which affect the production of lipoproteins in both the liver and intestine.

MTP transfers triglycerides (TG) onto apo-B during the assembly of very-low-density lipoprotein (VLDL), which is the precursor to low density lipoprotein (LDL). when sufficient lipid is transferred the lipoprotein secretion is inhibited. The MTP Inhibition prevents both hepatic VLDL and intestinal chylomicron secretion, and hence lowers plasma lipids.

LDL decrease due to MTP inhibition

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