n class we talked about the formation of VLDL lipoproteins in the liver. The ass

Question

n 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).

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

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. The basis of MTP (microsomal triglyceride transfer protein) inhibition as a hyperlipidemia drug is mainly going to avoid the "assembly of apolipoprotein-B" with lipoproteins result in no availbility of precursor molecules for "Mevalonate pathway" to carry out further cholesterol synthesis. This event is leading to low level of activity of HMG-o-A reductase activity (a rate limiting enzyme for Mevalonate pathway) finally result in reduced chylomicros and VLDL (very low-density lipoproteins). Therefore, LDL-C levels in the blood are going to "decrease"

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