Glycogen Flashcards
Discuss in general about the structure of glycogen
Glycogen is a large branched polymer consisting of D-Glucose residues that are mostly a1,4 except at branch points which are a1,6.
Branching usually happens at the interior
Discuss how we make glycogen
Glucose gets turned to glucose 6-phosphate by hexokinase as if we are starting glycolysis with the use of one ATP as usual.
Next, we need to separate it from glycolysis, so we quickly use a phosphoglucomutase to turn it to glucose 1-phosphate.
To further hide from glycolysis, Glucose 1-phosphate reacts with UTP to make UDP Glucose, which is made via UDP-glucose pyrophosphorylase (it is important to note that with this second masking event that inorganic phosphate is released. Cleaving this phosphate (ppi) to 2 pi’s and removing them helps push glycogenesis forward)
Now that we are on little glucose carries, glycogen synthase can take these glucose off of the UDP and add them to nonreducing ends of glycogen. UDP gets recovered and turned back to UTP with ATP
So how do we make branches of glycogen?
When a chain we are adding glucose to contains 11 or more glucose residues, an oligomer of 6-8 residues is removed from the nonreducing end of the chain and re-attached via an a1,6 linkage to an a1,4 via glucosyl 4:6 transferase at a spot that is 7 - 11 residues away (basically you just put part of your big stick coming off of the stick at another part of the stick, so now you have two branches instead of one big one)
How do we break down glycogen?
Basically the reverse of making it. We use glycogen phosphorylase to remove glucose residues at a1,4 bondsand with the help of Pi floating around turn them back to glucose 1-phosphate.
However the enzyme, because it is so big, can only work within 4 units of a branch point.
3 of the remaining 4 are removed by debranching enzyme 4:4 transferase. The last glucose, an a1,6, is hydrolyzed by a1,6 glucosidase to form free glucose.
This all keeps happening, forming glucose-1-phosphate in a 10:1 ratio
What is the fate of the glucose-1-phosphates?
Turned back to glucose-6-phosphate by phosphoglucomutase. In the liver, glucose-6-phosphatase releases the phosphate so glucose can enter the blood.
In muscle, we have to stop at glucose-6-phosphate because there is no glucose-6-phosphatase, meaning muscle can not contribute to sugar needs in the blood. The glucose-6-phosphate goes through glycolysis to become lactate or to CO2 and H2O to generate ATP
Discuss the 4 types of glycogen storage diseases
Very Poor Carb Metabolism
1 - Von Gierke - G6Pase deficiency causing glycogen buildup in tissue - hepatomegaly
2 - Pompe - Pompe trashes the pump - a1,4 glucosidase, systemic energy deficiency causes cardiomegaly
3 - Cori - Debranching a-1,6 glucosidase - Not a big deal, normal lactate and glucose production
5 - McArdles - Muscle glycogen phosphorylase - Excess muscle glycogen, painful cramps, rhabdo
Discuss hormone regulation of glycogen breakdown
Glucagon acts on the liver and epinephrine on the liver and muscle to stimulate degradation
They act via G proteins to activate adenylyl cyclase which turns ATP to cAMP. cAMP activates protein kinase A, which phosphorylates glycogen synthase to make it less active, and phosphorylates phosphorylase kinase.
Phosphorylase kinase turns phosphorylase b to a, which directly cleaves glucose residues.
Discuss hormonal stimulation of glycogen synthesis
When fed, glucagon is low, so no cAMP (phosphodiesterase turns cAMP back to AMP)
Insulin causes the dephosphorylation of phosphorylkinase and phosphorylase a to inactivate them.
Glycogen synthase kicks back up as more glucose enters hepatic circulation thanks to insulin activating phosphatase that catalyzes its activation.
Discuss the absorptive phase of startvation
Not actually starving.
You just ate, 0 - 4 hours ago.
Your blood glucose is coming from exogenous sources, everybody gets it, and the major fuel for your brain is glucose
Discuss the Postabsorptive phase
4 - 16 hours
Our main source of glucose is now glycogen and if needed, hepatic gluconeogenesis.
Everyone still gets glucose except the liver, and the muscle and fat start taking a little less than before.
Main brain fuel is still glucose (we still have plenty)
Discuss early starvation
16 - 1.5 days
We now use hepatic gluconeogenesis quite a bit and glycogen stores as well, although we are beginning to run out.
Everyone except liver still getting glucose and as before, muscle and adipose receiving less.
Brain still has sugar.
Discuss intermediate starvation
2 - 24 days
Alright now we are out of glycogen. We are doing gluconeogenesis in the liver and kidneys.
We also start rationing. The only things getting sugar are the brain, RBCs, renal medulla, and a very small amount by muscle
The brain uses glucose AND Ketone bodies now
Discuss what is happening with prolonged starvation
Prolonged starvation means we are still doing gluconeogenesis in the kidney and liver, and the brain, RBCs, and renal medulla are taking up sugar, but not the brain is using KBs more than glucose, and muscle isn’t getting jack.
How much ATP is used to store 1 glucose residue as glycogen?
2 ATP
Key regulatory enzymes for glycogenolysis and glycogenesis
Lysis = phosphorylase
Genesis = Glycogen synthase
