). Glycogen phosphorylases - pyridoxal-5 phosphate-dependent enzymes - catalyze the first and rate-limiting step of glycogenolysis to produce glucose-1-phosphate, which is converted to G6P via the reversible reaction carried out by phosphoglucomutases (Pgm). The alpha1-4 cleavage carried out by phosphorylases continues for as long as the glycogen chain is at least four to five residues from a branch point. The glycogen debranching enzyme (Agl) catalyzes the transfer of three glucose units to an adjacent branch; a second glucosidase reaction cleaves the alpha1-6 bond and removes the glucose unit from the branch point so that the phosphorylase activity can resume. In mammals, there are three phosphorylase isoforms - the muscle-, liver- and brain- specific enzymes; they are similarly regulated by covalent modification but are differently sensitive to allosteric regulation. The enzymes are dimers which in the resting state are in an inactive conformation. Phosphorylation of a single residue by phosphorylase kinase promotes a conformational change to the active state. Phosphorylase kinase is composed of four non-identical subunits of which the gamma subunit is the catalytic unit and the other three - alpha, beta and delta - are regulatory. Maximal activation of phosphorylase kinase is achieved by phosphorylation of the alpha and beta subunits by protein kinase A and by calcium binding to the delta subunit, which is calmodulin. Protein phosphatase 1 (Pp-1) dephosphorylates and inactivates both the phosphorylase kinase and glycogen phosphorylase enzymes. Note that this is also the phosphatase that dephosphorylates and activates glycogen synthase, the key enzyme of the glycogen biosynthetic pathway. G6P, which is an allosteric activator of glycogen synthase, acts as an allosteric inhibitor of glycogen phosphorylase. Thus, the two arms of glycogen metabolism are closely regulated at the level of the key enzymes involved in them. To see the ontology report for annotations, GViewer and download click here [click to see the ontology report for associated GO term - GO:0005980 and entry at Reactome - REACT_1008.1]...(less)