Question

Biochemical Signaling

i. Write out by hand the steps of the signal transduction pathway starting from binding of insulin to its receptor on a liver cell, leading to inhibition of glycogenolysis in that tissue. Include all steps in detail and hand write out this process. Look for hints as to the amount of detail on the Note Outlines with additional notes associated with Module 8. This also requires some review of module 5 on glycogen metabolism. Also remember insulin my cause multiple effects leading to this outcome.

Answer 1

Insulin acts by binding to specific glycoproteins, called insulin receptors of the target cell membrane. Each insulin receptor consists of two alpha and two beta peptide chains, all glycosylated and interlinked by disulphide linkages. Alpha chains project extra cellularly and possess cysteine rich residues consisting the insulin bindin gsite. Beta chains act as signal transducers. Binding insulin to the receptor stimulates its tyrosine kinase activity by increasing the Vmax of the ensyme. Tyrosine kinase is a specific type of protein kinase which phosphorylates the phenolic -OH group of specific proteins .

Insulin inhibits glycogenolysis by activating protein phosphatase 1 (PP1) and the enzyme phosphodiesterase. Both contribute to the inactivation of glycogen phosphorylase by reducing its phosphorylated state. Activated PP1 directly dephosphorylates glycogen phosphorylase a, reforming the inactive glycogen phosphorylase b, whereas phosphodiesterase converts cAMP to AMP, thus inactivating PKA and its ability to phosphorylate (activate) glycogen phosphorylase.