Presentation description

The enzyme glycerol 3-phosphate dehydrogenase (GPD1) is at the interface of |central carbon and glycerol metabolism. It performs the reversible reaction of |dihydroxyacetone phosphate to glycerol 3-phosphate while converting NAD+ to |NADH. Mutations in the GPD1 gene have been linked to the rare disorder |hypertriglyceridemia, known to elevate levels of triglycerides in the blood: however,|no treatment options are currently available for patients. While the crystal structure|of GPD1 has been solved, little is known about the allosteric regulators of the enzyme.| |Allosteric regulation is the regulation of an enzyme by the ligand binding at a site |other than the active site. Allosteric regulators are the most direct and efficient |regulatory mechanism in maintaining cellular homeostasis and could provide novel |therapeutic options for treating GPD1-related diseases such as |hypertriglyceridemia. Recently, the Rutter lab developed a method, called MIDAS, |which has identified a total of 830 known and putative protein-metabolite |interactions from 33 metabolic proteins. After screening GPD1 from rabbit muscle, |long-chain acyl-CoA came out as a hit. Here we show that long-chain acyl-CoAs |inhibit human GPD1 in vitro