Glycogen Phosphorylase

Isozymes

jaggedred.gif (2496 bytes)

There are three major classes of mammalian GPases, Liver, Brain, and Muscle. Each has a different role in the tissue it is in and a different role relating to the rest of the body. The catalytic mechanism for each isozyme remains the same universal reaction; however, the mechanisms of allosteric regulation vary somewhat from isozyme to isozyme. They are all converted from the b (inactive) form to the a (active) form by phosphorylation and dephosphorylation, but they use different ligands as regulators (Newgard et al 75). Table 1 shows the physiological and regulatory roles of the different GPase isozymes

Table 1: Physiological Roles and Regulatory Properties of GPase Isozymes

Isozyme Physiological Role Allosteric Control
Muscle Rapid mobilization of glycogen to phosphorylated glucose for energy for muscle contraction Covalent phosphorylation at Ser for activation; cooperative AMP activation; glycogen activation; glucose, purine, and G-6-P inhibition
Liver Provides free glucose for extrahepatic tissues (tissues other than the liver); regulates blood glucose Ser activation by covalent phosphorylation; weak non-cooperative AMP activation; glycogen activation; glucose, specific purine, and weak G-6-P inhibition
Brain Provides glucose for short anoxic or hypoglycemic periods Same as muscle except:

Potent non-cooperative AMP activation; weak G-6-P inhibition

Modified (Newgard et al 75)

Muscle GPase is the best known example of the GPases. Muscle GPase provides energy in the form of G-1-P.  Glycogen stores in the muscle are attacked by the GPase and converted to G-1-P. The activity of muscle GPase is the main focus of this paper because most literature published pertains to muscle GPase.

Liver GPase provides energy for the liver in the same manner as muscle GPase, but liver GPase has an extra role as well. The liver is responsible for maintaining blood glucose levels. The liver does this by converting glycogen polymers into glucose monomers that can easily diffuse through biological membranes (Newgard et al 77).

The final GPase isozyme is brain GPase. The physiological role of the brain enzyme is poorly understood. The brain stores far less glycogen than other tissues in the body, but it is the most active organ in the body. Therefore, it is thought that these glycogen stores are used as emergency fuel should blood glucose, the main fuel source for the brain, levels drop for some reason. It has been shown that brain glycogen levels drop and GPase activity rises when the body is stressed in such events as ischemia, anoxia, or convulsions (Newgard et al 77). However, because of the low glycogen levels in the brain, glycogen mobilization in the brain is a very temporary fix.

Blue2.gif (3665 bytes)Blue2.gif (3665 bytes)Blue2.gif (3665 bytes)Blue2.gif (3665 bytes)
Blue2.gif (3665 bytes)Blue2.gif (3665 bytes)Blue2.gif (3665 bytes)Blue2.gif (3665 bytes)