Question

1. One day at Acme Pharmaceuticals, your colleague Pat bursts into your lab and enthusiastically explains a hypothesis that developing an inhibitor to glycerol 3-phosphate acyltransferase (GPAT) would be a good way to counteract obesity. What is your biochemical opinion about this hypothesis?

2. One of the genomic DNA sequence variants that influences a person’s risk for having elevated plasma LDL cholesterol levels is in a gene called PCSK9. The PCSK9 protein is part of the vesicle sorting machinery that influences whether vesicles are recycled to the plasma membrane or fuse with the lysosome. Please propose a mechanism about how increased or decreased (your choice) PCSK9 function can lead to an increase in plasma LDL concentration.

Answer 1

Glycerol 3-phosphate acyltransferase (GPAT) is an enzyme which catalyse tryglyceride synthesis .Fat are stored in liver,skeletal muscle.Accumulation of fats lead to insulin resistance. This enzyme reduces that thus it can be used to treat type 2 .diabetes..Example of GPAT inhibitor, FSG67,.

PCSK9 Proprotein convertase subtilisin/kexin type 9 is coded by PCSK9 gene.This gene control regulation of cholesterol in blood..LDL receptors are plasma membrane glycoprotein that removes cholesterol rich LDL from the blood.PCSK9 regulates this LDL receptors.PCSK9 binds to LDC receptor on the surface leading to formation of PCSK9 receptor complex.there is redistribution of LDL receptors from the cell surface to lysosomes.LDLreceptors degrade in lysosomes So no recycling on cell surface.