Biochemistry: Citrate Leakage and Fat Storage

Hi, there!  I know I said that this time I was going to get into more biochemistry, but I lied a little.  We'll get to it in a short while, but first I'd like to talk a little bit more about the effects of ketosis, because today was...interesting.

I confess, I probably should have had more water, especially since I went to a concert (Imagine Dragons for those of you who are interested--it was awesome by the way).  So, I was kind of behind today in terms of hydration.  You know when you stand up and haven't had enough water to drink, and your vision gets all tunnelly and you start to get dizzy?  That happened every time I stood up today.  So, the moral of the story: even if you don't feel like drinking anything, you should because you'll just be miserable later.

This is your friend.

 In my last post, I think it sounded like as soon as you're ketotic, then boom, everything is wonderful.  While you are burning fat due to less glucose being present in the bloodstream, your body actually takes a little bit of time to adjust to the fact that glucose isn't there anymore.  Basically, for about 2 weeks, your body says, "Hey, where's all that glucose you were getting from eating all those carbs?  This is really weird getting energy from fat and can I please get some glucose right now."  This means that, when you exercise, after you burn through the small amount of glucose present in your blood on a low carb diet, your body just kind of grinds to a halt and goes "What do I do now?!"

Welp, sorry!

I say this because earlier this evening, I was in my karate class doing a pretty strenuous kicking drill (involving lots of jumping roundhouse kicks--my worst enemy).

This, but in the air.  Also, why is he in a suit??

About two-thirds of the way through, I got really, really tired.  At that point, like I said above, my body had burned through the small amount of carbs I had eaten and just decided to hold out for some more.  The good news is, though, that once you hit that point and push through it, you're burning through your fat stores.  By next week, I should start seeing different results when my body actually adjusts.

Anyway, moving on to biochemistry, which is much more exciting.  We're going to look at two things: citrate leakage (which is easier and a lot less disgusting than it sounds) and the creation of triglycerides (fat) from glucose.

I'm going to say something that will make a lot of biology students cringe.  Are you ready?

The Krebs Cycle.

It's so...ugly.

But we're not going to worry about a lot of it.

Woohoo!

The Krebs Cycle takes place in the mitochondria of the cell, which supplies power to the rest of the cell.  Glucose is moved into the mitochondria from the bloodstream (we'll get into that in a later post), where the carbons making up the molecule are rearranged until we get a molecule called Acetyl-CoA, circled above.  Acetyl-CoA then enters into the Krebs Cycle, and as the molecules are shifted around, ATP gets produced, which provides energy.

In a person who eats a healthy amount of carbohydrates, the cycle produces just enough ATP to power the body, while using all of the glucose in the blood.  Now, let's say you decide to get a piece of cheesecake from the Cheesecake Factory.

This has enough calories for an entire lifetime.  It also has 136g of carbohydrates, which is three times the amount I'm allowed to eat in a day.

That's waaay more glucose than you need at once.  Once all of that glucose is turned into Acetyl-CoA, though, it all starts to go through the Krebs Cycle.  Since you have such a huge amount of glucose, not all of it will go through the entire cycle, since it takes a fair amount of energy to create ATP, which would be a complete waste.  So, the cycle stops at citrate, also circled above.  All the excess citrate that accumulates in the mitochondria is shipped off to the cytosol of the cell.

And that is citrate leakage.  Doesn't look too important, right?  Well, the important part comes with what happens to the citrate once it leaves the mitochondria.

Let's look at a cell:

Marvel at its well-drawn beauty.

The citrate doesn't just hang out in the cytosol, though, since the cell doesn't like freeloaders.  It is turned back into Acetyl-CoA.

It then reacts with an enzyme called Acetyl-CoA Carboxylase (ACC for short because that's a pain to type out).  ACC is turned on in the presence of insulin, which is present because of all the excess glucose you got from that cheesecake (you pig, you).  This creates a molecule called Malonyl-CoA.

Malonyl-CoA then reacts with an enzyme called Fatty Acid Synthetase (FAS) to form a long chain fatty acid.

Once three of these are made, they are combined into a molecule called triglyceride, aka fat.  This fat is then stored as ectopic fat in muscle tissue and the liver.

This is especially problematic for type II diabetics.  Their insulin levels are extremely high due to an insulin resistance--a healthy person has a fasting insulin level of about 5, while a type II diabetic will have a fasting insulin level of 50 or 60.  In this case, their insulin levels will always be very high, which means that ACC will always be turned on.  This means that, essentially, their bodies are in a constant state of fat storage!  Any glucose that enters the bloodstream will be turned into fat.  Giving them more insulin helps keep their blood glucose down, but it also maintains the entire cycle of fat storage.  This is a problem.  So, what is a solution?

Get outta here!

 By lowering the amount of insulin, the fat-storing cycle is diminished.  This doesn't allow the body to store more ectopic fat, which solves a whole host of problems.  How do you lower insulin, then?  By not eating carbs.  The pancreas doesn't release insulin without glucose, so by lowering the amount of glucose, the amount of insulin goes down, which shuts off ACC.

I would go into more detail about Malonyl-CoA and what it does, but I've been rambling for long enough.  In an effort to keep this post from turning into a novel, I'm going to cut it here.  I'll continue this stuff next time.  See you then!