Evidence for the Quercetin Binding Site of Glycogen Phosphorylase as a Target for Liver-Isoform-Selective Inhibitors against Glioblastoma: Investigation of Flavanols Epigallocatechin Gallate and Epigallocatechin.

Glycogen phosphorylase (GP) is the rate-determining enzyme in glycogenolysis, and its druggability has been extensively studied over the years for the development of therapeutics against type 2 diabetes (T2D) and, more recently, cancer. However, the conservation of binding sites between the liver and muscle isoforms makes the inhibitor selectivity challenging. Using a combination of kinetic, crystallographic, modeling, and cellular studies, we have probed the binding of dietary flavonoids epigallocatechin gallate (EGCG) and epigallocatechin (EGC) to GP isoforms.

Kinetic and Structural Studies of the Plastidial Phosphorylase.

Kinetics and structural studies of the plastidial phosphorylase (Pho1) revealed that the most active form of the enzyme (Pho1ΔL78) is composed by two segments generated by proteolytic degradation of an approximately 65-residue-long peptide (L78) approximately in the middle of the Pho1 primary structure. Pho1ΔL78 is 1.5 times more active than the nonproteolyzed enzyme in solution and shows stronger specificity for glycogen, α-d-glucose, caffeine, and β-cyclodextrin than Pho1.

Multidisciplinary docking, kinetics and X-ray crystallography studies of baicalein acting as a glycogen phosphorylase inhibitor and determination of its' potential against glioblastoma in cellular models.

Glycogen phosphorylase (GP) is the rate-determining enzyme in the glycogenolysis pathway. Glioblastoma (GBM) is amongst the most aggressive cancers of the central nervous system. The role of GP and glycogen metabolism in the context of cancer cell metabolic reprogramming is recognised, so that GP inhibitors may have potential treatment benefits.

Tissue dissection with saline injection: application in thyroid surgery.

Postoperative hypoparathyroidism is a thyroidectomy complication. The effect of this complication cannot be accurately quantified. The incidence of hypoparathyroidism after total thyroidectomy has high variability in the literature, between 7 and 37%.