Glycogen Synthetase (and Branching Enzyme)

Abstract

The second enzyme capable of the synthesis of α-1,4 linkages of glycogen is glycogen synthetase*. Unlike phosphorylase, it is synthetic both in vitro and in vivo, it seems to have similar properties in all tissues including CNS, and can not degrade glycogen; it is now proved to be the only synthetic enzyme under normal in vivo conditions. It has several features in common with those of phosphorylase, however. Thus it exists in two forms, an active (I, for independent) and an inactive (D, for dependent); both are interchangeable and regulated by hormonal and nonhormonal factors. The I-form is further activated by G-6-P; at pH 7.0 it doubles the activity and at pH 8.5 it increases it 5–12 fold (Leloir, 1964). Furthermore, the D-form can be transformed to the I-form, not by adding phosphate as in the case of phosphorylase, but by removing it. The enzyme responsible for this is synthetase (transferase)-D-phosphatase. The reverse transformation can also be achieved, and, again, unlike the case of phosphorylase, by a synthetase (transferase)-I-kinase in the presence of ATP. The kinase, as that of phosphorylase, is stimulated by cAMP which, of course, is in turn, influenced by adenyl cyclase and phosphodiesterase and all the factors that influence them. Thus cAMP stimulates active phosphorylase formation, but inactive glycogen synthetase, formation. “This inverse polarity in a biological sense is a key point...” (Larner et al., 1968).