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If the energy to keep our cells alive and for us to carry out our everyday activities comes from the food we eat, how come we're not broke (of energy) when we wake up in the morning after 8 hours of sleep? Or how do we still have energy after a prolonged period of fasting? Let's find out!!

The concept of a savings account!!

In the same way that a lot of us try not spend all the money we earn in one go and instead try to save up some for an emergency situation, or for that car, or a house, or whatever it is that you want at some point in your life, our body does the same.

When we eat, more often than not we have an excess supply of nutrients, namely carbs, fats and proteins. Our body most often does not need to use all of that energy in one go. Instead, the body creates a savings account for the excess nutrients!! Our body Constantly needs energy, but we're not constantly eating. And that's why we have the storage of nutrients and the body has mechanisms in place to tap into these stored nutrients to supply the constant energy needed!!

Glycogen

Glycogen is the body's direct carbohydrate reserve. It's made from joining together hundreds of thousands of glucose molecules into a long chain form. Well, you might ask, if it's just all glucose molecules, then why exactly do we need glycogen? Why don't we just store glucose as it is?

Why do we need Glycogen as the storage form

Free glucose is an osmotic molecule, meaning it draws water to itself. If all your cells were packed with glucose, it would draw too much water from the body into the cell and the cells would all start to swell and eventually burst if it swells too much!! Now we can't have that happening in an attempt to store energy, can we? Which is why, we convert the osmotic glucose molecules into glycogen, a molecule that doesn't draw as much water as glucose does. But it is important to note that, because glycogen is a water soluble molecule, it will till also draw some water, which is why we can not keep synthesizing glycogen indefinitely from the excess glucose/carbohydrate that we eat!! But first, let's look at how glycogen is synthesized.

Glycogen Synthesis

Glycogen is synthesized around a core protein called glycogenin. Glycogen synthesis begins with addition of glucose molecules to this core protein, and then further molecules of glucose keep getting added to the glucose chains.

Image from Kaplan USMLE Step 1, Biochemistry Lecture Notes. Annotations done by me.

As we've discussed in episode 1, glucose can be notorious and move in and out of cell which might create issues of not having glucose in the cell when we need to use it!! So, similar to the glycolysis pathway, glucose needs to be phosphorylated first and once it's trapped inside the cell by phosphorylation, we can proceed to the next step of glycogen synthesis.

Now recall, the enzyme Glucose-6-phosphatase phosphorylates glucose to Glucose-6-phosphate (G6P). The number "6" indicates that the phosphate ion was added to the 6 position carbon atom of the glucose. (Sorry, but this is a bit of necessary technical detail). Now, glucose with a phosphate at the 6th position carbon is destined to go into glycolysis. But if we don't need anymore energy production at some point, we don't really need the glucose to go into glycolysis. Instead we need it to go into the glycogen synthesis pathway.

An enzyme called phosphogluco-mutase changes the position of this phosphate from the 6th position to the 1st position carbon atom to produce Glucose-1-Phosphate (G1P).

Image from Kaplan USMLE Step 1, Biochemistry Lecture Notes. Annotations done by me.

Now that we have our glucose in the form we want, we need to activate this G1P. This is done by adding UTP (uridyl triphosphate) to G1P. what this does reaction does is, it knocks off two phosphates from the initial UTP molecule in the form of Pyrophosphate, and joins the rest of the molecule to the G1P molecule forming something called UDP-Glucose. This joining of G1P to the rest of the UTP needs energy and this energy is provided by the hydrolysis of the pyrophosphate molecule that we just created!!

This step is necessary because our star engyme, Glycogen Synthase can work better on UDP-Glucose, and not directly on the raw G1P and it's easier to remove UDP from the glucose before adding it to the growing glucose chain. That's the function of the enzyme glycogen synthase. It simply removes the UDP group from the UDP-glucose and joins it to the growing glucose chain, making the chain one glucose molecule longer. And it keeps doing this, making long glucose chains growing out from the core glycogenin protein, one glucose at a time!! If you guys need some inspiration sometime in life, there's inspiration right there, happening inside your body!!! Don't get too overwhelmed by life, take is one step at a time, in a similar way as glycogen synthase is creating this wonderful glycogen molecule, one glucose at a time!!

Branching the chains

Now, if we keep letting these chains grow in a linear fashion, it will grow too long at take up a lot of space. But when we're synthesizing storage molecules, we need to make it as compact as possible to be able to store more in the available space.

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So what we do is, we break off the chains at some point, like this :

Image from Kaplan USMLE Step 1, Biochemistry Lecture Notes

And rejoin it to the chain as follows :

Image from Kaplan USMLE Step 1, Biochemistry Lecture Notes

Slight detail to be aware of is that, the bonds between the glucose molecules in the linear chain and at the branch point are not the same bond and will need different enzymes when we break it down. But that's for an entirely different post.

Now you see that the molecule will be taking up lesser space and become more compact as a result of this branching and we can add more molecules of glucose to the glycogen molecule, thus increasing availability of glucose when we need to tap into the energy reserves!! This step is carried out by an enzyme called Branching Enzyme, DUH!!

But we can't keep synthesizing glycogen indefinitely....

As I have mentioned above, there are limitations to glycogen synthesis because even after branching, it's not as compact as we would like it to be, as it draws some water to itself and takes up extra space. we need something better. We need something that is not soluble in water and will not draw any water. Can you guess what substance might fulfill all these requirements? Hint : The answer is in the title.

Yes, fat!! Fat, more specifically triglyceride are extremely compact molecule and are completely insoluble in water, thus it draws no water to itself and is the most efficient for of energy storage in our body. And fortunately/unfortunately, glucose can enter into the pathway of triglyceride synthesis. The exact details will be discussed in the next post, but this is why it is said, eating too much carbohydrates can make you fat. This is also why, people trying to bulk up increases their carbohydrate intake, beside many other steps.

# Synthesis of triglycerides for storage will be discussed in episode 4. Stay tuned.

Resources :
Lippincott's illustrated Reviews Biochemistry, 5th edition
Kaplan USMLE Step 1 Biochemistry Lecture Notes
Khanacademymedicine

If you enjoy medical topics, or want to learn how different things work in this amazing human body, please make sure to follow me at @simplifylife

Peace!!