Using the Glycogen storage disease mnemonics is one of the fastest ways to memorize and learn all the complications on Glycogen metabolism.
Once you unlock the codes, learning and remembering every important knowledge on this metabolism topic will be a breeze!
In case you’re new here, this blog post is a part of our Snacky Medmonics which focuses on creative mnemonics to help you learn well in medical school.
So here’s what we’re going to do in today’s topic;
- An overview of Glycogen metabolism
- Main concepts on glycogen breakdown and synthesis and
- An easy-to-remember mnemonic for exam purposes!
Let’s get to business right away!
Overview
Glycogen is the storage house for the energy producing molecule- glucose. It is synonymous with starch which stores energy in plants. Glycogen is mainly found in the muscles and liver.
And just like you know, if you have a a storage house for things, like a fridge for example, it means you can keep things in, and also take them out whenever the need arrives! And that’s exactly how glycogen works!
During a well fed state, just after eating a delicious meal or crunchy food, our body uses some of the glucose to produce energy through a process called glycolysis.
However, the excess glucose that is not utilized will be stored as glycogen.
In the same vein, when you’ve not eaten for a period of time, let’s say 18 hours, the tissues of the liver and kidney begin to break down the glycogen to produce glucose and ATP. So that’s it!
In the liver, the glycogen is broken down to glucose in order to bring the blood glucose levels to equilibrium.
However, in the muscle, it’s immediately converted to ATP following one of the intermediates of glycolysis.
Note the difference.
Metabolism of glycogen
The storage house, glycogen, can be explained using 2 major headings; the synthetic phase which is also called glycogenesis and the catabolic phase- glycogenolysis.
Let’s jump into the details!
Glycogenesis – Storage Disease Mnemonics
What comes to mind when you hear genesis? Build up right? Absolutely!
Glycogenesis is coined from two words; glycogen and genesis, and from it, you can easily denote that it is the process by which glycogen is formed from glucose. In simpler terms, it’s the buildup of glycogen from glucose.
Site: Glycogenesis occurs majorly in the liver and the skeletal muscles. They have their unique reactions. And you should know that in the liver works to add up blood glucose levels while that of skeletal muscles is to generate ATP.
Also Read: How to study well in medical school
Reactions
1. Phosphorylation
Glucose is the first phosphorylated using ATP to form glucose -6-phosphate. But the enzyme depends on the site of the reaction.
In skeletal muscles and all other tissues, the Hexokinase catalyses this process, but in the liver? It’s Glucokinase!
Glucose + ATP > Glucose-6-phosphate + ADP
2. Changing phosphate positions
The phosphate on the carbon number 6 of the glucose-6-phosphate is transferred into the carbon number 1 using the phosphoglucomutase enzyme, and the result is Glucose-1-phosphate.
Glucose-6-phosphate > Glucose-1-phosphate
3. Activation of glucose
The glucose-1-phosphate is now converted into the activated glucose by reacting with the Uridine Triphosphate nucleotide. This is a very important reaction and the coenzyme is Pyridoxal phosphate. Take note of this coenzyme!
The result formed is Uridine Diphosphate glucose (UDPglc) and the enzyme is Uridine Diphosphate glucose pyrophosphorylase.
Next the carbon 1 of the UDP-glucose reacts with the carbon number four of a glycogen terminal glucose residue or glycogen primer to liberate UDP. The enzyme is glycogen synthase.
The glycogen synthase continues forming repetitive glycosidic bonds between 1 and 4.
Note that each extension uses 2 ATP molecules. The first was in the phosphorylation and the second now in generating the UDP.
4. Branching – Glycogen storage disease mnemonics
At every 8-10 residues, a 1-6 glycosidic branch is formed by the Amylo-1-4 to 1-6 transglucosidase.
So with all those processes, glycogen is formed having glycosidic alpha 1-4 and 1-6 glycosidic bond with branching at every 8-10 glycosyl residues!
Now let’s move over to the glycogen breakdown!
Glycogenolysis
Whatever goes up must surely come down right? While that’s true, the process of glycogen build up and breakdown are not the same.
Glycogenolysis from the words “glycogen” and “lysis” is the process by which glycolysis is broken down to produce glucose.
State: This process occurs when one is starving.
Reactions
1. Glycogen phosphorylase
Glycogen is first broken down by phosphorylation (phosphorolytic cleavage) to produce glucose-1-phosphate.
It starts cleaving the Amylo-1,4- glycosidic bonds until the fourth residues to the 1-6 bond. The enzyme catalysing this reaction is glycogen phosphorylase.
Glucose + ATP> Glucose-1-phosphate.
The four remaining glucose residues are then transferred from the 1-6 glycosidic branch in order to expose the branch point. The enzyme that catalyzes this reaction is the alpha 1-4 to 1-4 glucan transferase.
Now that the alpha 1-6 glycosidic bond is open, the debranching enzyme, Amylo-1-6-glycosides, splits it hydrolytically into one molecule of free glucose instead of glucose-1-phosphate.
Remember, there’s still the glucose-1-phosphate? So the next reaction is the phosphoglucoisomerase reaction which catalyzes the transfer of the phosphate from the C1 to C6 thus forming glucose-6-phosphate.
However, the fates of glucose-6-phosphate is different depending on the site of action:
Liver
Glycogen metabolism in the liver is mainly to restore the blood glucose levels in the body. Therefore, the glucose-6-phosphate is converted into glucose directly by a special enzyme called glucose-6-phosphatase present only in the liver.
Skeletal muscles
Glycogen breakdown in muscles doesn’t contribute to blood sugar levels directly. Instead the glucose-6-phosphate being an intermediate enters into the glycolytic cycle forming pyruvate and lactic acid.
Important Enzymes
Now your known all that, let’s look at the important enzymes;
- Glycogen synthase
- Glycogen phosphorylase
- Debranching enzyme
So, the Glycogen storage disease mnemonics depend on thee enzymes outline above.
Now let’s get into them immediately!
Glycogen storage disease mnemonics Simplified
There are 7 types in the glycogen storage disease mnemonics which are:
- Von Gierke
- Pompe
- Cori
- Anderson
- Mcardle
- Hers
- Taurai
Now the mnemonic I use to remember them is actually a mental coding system.
But before we start, let’s talk about Typhoid. You know it’s a severe disease right? But what causes it? You’d find out that Typhoid is caused by a lot of things. Hence, the GSDs have several types. And in this mnemonic, The Vice President is making hers.
Here’s the mnemonic;
- Vice- Von Gierke’s disease
- President- Pompe
- Chi- Cori
- Amaka- Anderson
- Makes- Mcardle
- Her- Hers
- Typhoid- Taurai
Now let’s jump into details on the Glycogen storage disease mnemonics!
Type I: Von Gierke’s Disease/ GSD 1
Von Gierke’s disease is the first type in the Glycogen storage disease mnemonics. It’s as a result of deficiency of the Glucose-6-phosphatase which is found in the liver and mucosa of the intestine.
Recall, the function of this enzyme is to breakdown glycogen to produce glucose for the blood. But if the enzyme is deficient? Here are the implications;
Clinical implications
- Hypoglycemia: the liver’s function is to produce glucose when it’s level in the blood is low. But now that there’s a deficit of the enzyme- Glucose-6-phosphatase, there’d be low blood glucose which is referred to as Hypoglycemia.
- Hepatomegaly: the liver can perform its usual gluconeogenesis pathways, but when glycogenolysis is disrupted, it results in glycogen accumulation in the liver which causes hepatomegaly.
- Acidemia/Lactic acidosis: in severe conditions, catecholamine is secreted due to hypoglycemia which further causes the catabolism of muscle glycogen into lactic acid.
- Dwarfism: children with GSD-1 May have dwarfism because the low blood sugar inhibits insulin which further inhibits protein synthesis for growth.
Further complications of the Von Gierke’s Glycogen storage disease mnemonics include xanthoma, keto acidosis, Hyperuricemia.
Type II: Pompe’s disease
This glycogen storage diseases occurs in the lysosomes of cells in the body. It’s as a result of deficiency of the alpha 1-4 and 1-6 glucosidase enzyme.
An important complication from this disease is heart enlargement (cardiomegaly). There’s also hypotonia of the muscles causing muscular weakened and muscle dystrophy. Note; it doesn’t result in hypoglycemia.
Type III: Forbe’s disease
The third one that falls among the glyocgen storage disease mnemonics is the Cori/Forbes disease.
Think about wealthy billionaires on Forbes list. You’d notice that they don’t rely on one source of income, instead they branch, as in “de branch”.
So you can use this ideology to remember the cause of Forbes disease which is the deficiency of the debranching enzyme- amylo-1,6- glucosidase.
Do you remember it’s function? It splits the Dextrin to form glucose. So a deficiency of the enzyme resulted in;
- Hepatomegaly
- Fasting hypoglycemia
- Accumulation of branched polysaccharides ie the limit dextrin
- Weakness of muscle
Type IV: Anderson’s disease
Let’s take the next glycogen storage disease mnemonic: Anderson’s disease.
Imagine that Anderson is a poor man and like we said poor people don’t branch their sources of income. So, these folks lack the branching enzyme. Get the gist?
The branching enzyme in glycogen metabolism is Amylo-1,4 >1,6 transglucosidase.
Let’s recap its function again;
After the activation of Glucose as in UDPglucose, and the glyocgen synthase has a formed a bond between the C1 and the C4 of the glycogen primer molecule, the branching enzyme comes into play.
The branching enzyme forms the amylo-1,6-glycosidic bond at every 6 glucose residues. This elongating the chain.
So if the enzyme is deficient in an individual? It’ll lead to hepatomegaly, splenomegaly, hypoglycemia, cirrhosis, and an abnormal glycogen haven’t few branch points and looks like amylopectin.
Type V: Mcardle’s Glycogen storage disease mnemonics
Anytime you think about Mcardle in regard to the glycogen storage disease mnemonics, you should remember M, that is the first letter, stands for Muscle phosphatase.
Remember the function of the enzyme?
In Glycogenolysis, it breaks the 1-4 glycosidic bonds in glycogen releasing the glucose as glucose-1-phosphate until it reaches 4 residues to the 1-6 glycosidic bond.
So when the enzyme is deficient? It results In low glucose in the muscle, muscle cramps during strenuous exercises, pain, and frequent weakness, stiffness, high muscular glyocgen instead of ATP.
Type VI: Hers disease
H in Hers stands for Hepatic which means Liver.
So when you think about Hers glycogen storage disease mnemonics, what should come to your mind is Liver phosphorylase.
The phosphorylase enzyme whose normal function is to break down glycogen to glucose-1-phosphate is deficient. Hence leading to complications such as accumulation of glycogen in liver (hepatomegaly), mild hypoglycemia, mild acidosis.
Type VII: Tarui Glycogen storage disease
Glucose is first phosphorylated to Glucose-6-phosphate by Hexokinase. Next, Phosphofructoisomerase catalyzes it’s isomerisation to Fructose-6-phosphate.
Then what next? Come on, we’re talking about the glycolytic pathway!
Yep, so, phosphofructokinase comes in to phosphorylate the C1 to Fructose 1,6 bisphosphate. And then it goes on and on, until ATP is finally produced after the TCA cycle!
That would have been the normal fate of glucose-6-phosphate in the muscle after being converted from glucose-1-phosphate by phosphatase enzyme.
But…
In Tarui’s glycogen storage disease, the Phosphofructokinase enzyme PFK-1, is deficient!
So it results in accumulation of Glucose and fructose-6-phosphate in the muscles. And is similar to Mcardle’s GSD.
So that’s all on the Glycogen storage disease mnemonics!
Regulation of Glycogen
Another important thing to know under glycogen metabolism is how the process is regulated.
Have you ever wondered why it’s breakdown and synthesis don’t occur at the same time?
It’s because Glycogen synthase and Phosphorylase, the main enzymes in glyocgen control occur in opposite directions and mechanisms!
Let’s jump into details;
1. Glycogen Phosphorylase
Heck! This isn’t the first time I’m saying this, but let’s recall again. This enzyme breaks the 1-4 glycosidic bonds of glycogen releasing glucose in phoshorylated forms (glucose-1-phophate) hence it’s name.
So, it has two forms; an activated form a which is phosphorylated and an inactivated form b which is dephosphorylated.
The enzyme that activates it is Phosphorylase kinase while the one that deactivates it is Phosphoprotein phosphatase.
Since glycogenolysis is to produce glucose for ATP in the body, excess energy in the body or hormones related to such, inhibits the enzyme.
This includes;
- ATP
- Glucose-6-phosphate
- Free glucose
- Insulin
Activators
cAMP
Cyclic Adenine Monophosphate is formed from ATP by Adenlyl Cyclase responding to hormones such as glucagon, norepinephrine, epinephrine.
This enzyme further activates the Phosphorylase kinase to activate the Phosphorylase enzyme b to a.
Glucagon
However, the cAMP is formed depending on hormonal response and the site of secretion.
In the liver, Glucagon is the chief hormone which signals the formation of cAMP to activate PKA because of low glucose levels.
Norepinephrine
But in the skeletal muscles? Norepinephrine also Adrenaline, the hormone secreted in response to fear, signals the production of cAMP for immediate ATP in muscles for activity.
2. Glycogen synthase
Like the former regulating enzyme, glycogen sythase occurs in both active and inactive forms. But this time, it’s the opposite.
What do I mean?
The active form a is dephosphorylated while inactive form b is Phosphorylated. You get the gist? And they also have the same activators and inhibitors but in opposite directions.
That is, PKA which activates glycogen phosphorylase, also phosphorylates Glycogen synthase thereby rendering it inactive. The same manner goes for the Phosphoprotein phosphatase.
Furthermore, the hormones and molecules that inhibits glycogen phosphorylase, activates the synthase enzyme. That is, insulin, ATP, free glucose, etc.
So that’s all on Our Simplified Glycogen metabolism!
Glycogen Storage Disease Types Mnemonics Summarized
Here’s a summary of everything
| Type | Glycogen storage disease | Mnemonics |
| I | Von Gierke’s | Vice |
| II | Pompe | President |
| III | Cori/Forbes | Chi |
| IV | Anderson | Amaka |
| V | Mcardle | Makes |
| VI | Hers | Her |
| VII | Tarui | Typhoid |
Also Read: Brachial Plexus mnemonics for easy recall
Review on Glycogen storage disease mnemonics
Glycogen is a very important molecule which helps to regulate blood sugar and produce energy for muscular activities.
In this snacky medmonic series, we’ve talked extensively on its metabolism as well as given snacky mnemonics for you to enjoy and remember the major points!
Remember, Vice President Chi Amaka Makes Her Typhoid!
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