week 4- glycogen synthesis

major storage site of glycogen

muscle and liver tissue, more in muscle

function of glycogen stores in liver

metabolic glucose reserve that can be used to maintain blood glucose concentrations during a fasting state. liver breaks down glycogen to glucose units and releases it into the blood

function of glycogen stores in muscle

glycogen stored here can only be used as an energy source in the muscle, missing enzyme to release glucose into the blood

purpose of highly branched structure of glycogen

increases solubility of glycogen in cytoplasm, so can store more glycogen int he cell, contains many terminal glucose units which can easily be grabbed and released by specific enzymes, which allows glycogen to be a readily available source of glucose either maintain blood glucose in the liver or muscle concentrations

glycogen synthesis

post-prandial state when insulin is high to store excess dietary glucose as an energy substrate that can be drawn upon when little glucose is coming from the diet in fasting state

where does glycogen synthesis take place?

in the cytosol of liver and muscle tissue

glycogen synthesis- step 1

glucose to G6P (hexokinase or glucokinase rapidly phosphorylate to trap it in the cell), to G1P by enzyme phosphoglucomutase

glycogen synthesis- step 2

glucose must be activated prior to incorporation, energy from hydrolysis of UTP is used to ‘activate’ glucose, transfer high energy P from UTP to glucose to form UDP-glucose, glucose is incorporated into glycogen as UDP-glucose

glycogen synthesis- step 3

glycogen synthesis requires a primer, either existing glycogen or glycogenin- short sequence of glucose residues connected by alpha-1,4 glycosidic bonds

glycogen synthesis- step 4

glucose units added from UDP-glucose by alpha-1,4 glycosidic bonds by glycogen synthase

glycogen synthesis- step 5

2hen chain reached ~11 units, a 5-8 residue piece is cleaved by the branching enzyme, then re-attached to a glucosyl unit on the interior of the glycogen molecule by an alpha-1,6 bond. The new branch point must be at least 4 residues away from a pre-existing branch point

control of enzyme activity- short term

within seconds by changing enzyme activity, can be used to alter the rate of a metabolic pathway to respond acutely to a particular metabolic scenario, changes: substrate availability, cofactor availability, allosteric inhibitors and activators, and reversible covalent modification

control of enzyme activity- long term

minutes/hours/days by changing enzyme amount, increased and decreased degradation, increased and decreased synthesis (transcription and translation)

functions of phosphorus

major component of bone and teeth, main intracellular anion in all body cells, energy production and storage, cellular component, and enzyme phosphorylation- covalent regulation of enzyme activity

regulation of glycogen synthase- kinase

adds phosphate group, converts active glycogen synthase to inactive form

regulation of glycogen synthase- phosphate

removes phosphate group, coverts inactive glycogen synthase to active form

regulation of glycogen synthesis

- hormonally driven, glucagon and insulin alters the phosphorylation state of glycogen synthase

regulation of glycogen synthesis- insulin

stimulates protein phosphatase (removal of phosphate group) to activate GS through insulin receptor signaling cascade to promote UDP-glucose to glycogen

regulation of glycogen synthesis- glucagon

increase glucagon during fasting (liver) or epinephrine with exercise or stress (muscle) enhance cAMP increases phosphorylation and inactivation through protein kinase A

feed forward and feedback regulation- G6P

GS is allosterically activated by G6P which can stimulate the phosphatase to convert glycogen synthase to its active form (it also inhibits glycogen breakdown by inhibiting glycogen phosphorylase)