The Key to Burning Fat

We will now continue our scheduled broadcasting about Malonyl-CoA.

Hey, everyone!  We're going to continue with some more biochemistry today, because understanding biochemistry really helps when you try to treat a patient.

Here's that scary chart I made before, as a refresher:

Fat production and storage.

As a quick review, when the body eats too much glucose, citrate is dumped from the mitochondria into the cytosol of the cell.  It is then turned back into Acetyl-CoA, which reacts with Acetyl-CoA Carboxylase (ACC) to form Malonyl-CoA.  Then, Malonyl-CoA reacts with Fatty Acid Synthetase (FAS) to form long chain fatty acids, which are turned into triglycerides.  Whew!

Malonyl-CoA actually has two functions within a cell.  First, it reacts with FAS to form triglycerides when you eat too much sugar.  Second, Malonyl-CoA is in charge of whether or not the mitochondria is able to burn fat.

Wait, what?  Why does something that causes the production of fat also make you burn fat?  Well, in order to explain, I'll go back to my handy-dandy freehand charts.

You know you love them.

This is a metabolizing cell.  The body doesn't expend energy for no reason.  When glucose (or glycogen from the liver) is present, it will burn that glucose for energy.  In the presence of Malonyl-CoA,

By eating too much glucose.

The CPT1 gate closes.

Aaaand it's gone.

CPT1 is a transport protein in the mitochondrial membrane that allows fat to enter the mitochondria to be burned for energy.  In the presence of Malonyl-CoA, CPT1 closes so that the body doesn't waste energy creating fuel it doesn't need.  So, basically, by eating too much sugar, you literally can't burn fat!

Once Malonyl-CoA decreases, CPT1 opens, allowing the body to shuttle fat from fat cells and ectopic fat into the mitochondria to create ATP.

Now, let's relate this to Type II Diabetes.  If you look at the first chart,

This one.

You can see that, when insulin levels are higher, ACC is activated.  This is actually epigenetically regulated, so when more insulin is present, more ACC is produced--this really isn't related to what we're doing at this point, but I think it's interesting.  In patients with diabetes, insulin levels are very high, which means that Malonyl-CoA is produced when they eat glucose.  Since ACC is never turned off and Malonyl-CoA is always produced, CPT1 is always closed.  So, ectopic fat will never be used for fuel.

If you bring the insulin levels down, CPT1 is open, allowing fat to be mobilized and burned off.

Next time, I'll get into how insulin levels can be brought down, and why the real problem is ectopic fat.  See you then!

We interrupt this biochemistry lesson in order to bring you some personal experiences with ketosis, featuring our special guest, AMPK.

Hey guys, I have a slight change of plans in regards to today's post.  I know I said last time that I was going to talk some more about Malonyl-CoA, but in light of recent events (i.e. yesterday: literal hell), I've decided to talk about some of what I experienced, with a generous side helping of biochemistry to go along with it.

As part of the diet plan Dr. Walker has put me and his medical students on, I have to hike Camelback every Friday.  For those of you not living in Arizona, it's this thing:

Geddit, cuz it looks like a camel.

It's a pretty tough hike, putting it mildly.  A lot of it looks like this.

Eww.

Anyway, let's get on to some biochem!  AMPK is very, very important.  It's stimulated by several things: when ATP drops to ADP and then AMP, from the body using ATP as energy by breaking bonds; when calcium builds up in your muscles when they move, through voltage-gated calcium ion channels that make the muscle contract, for those of you who are interested; and from the presence of certain protein kinases.  This is why exercise is so important to being healthy, since it stimulates AMPK.

So, what does AMPK do?  Remember this scary chart I drew in the last review?

This one.

 Well, AMPK phosphorylates Acetyl-CoA Carboxylase (ACC), in the way that reduced insulin levels does.

Yay!

This way, no Malonyl-CoA is produced, which means no fat is produced.  It also allows fat to be mobilized from fat cells to the mitochondria to be burned for energy through beta oxidation, but that'll be saved for the next post.

There's a catch, though.  There's a certain concept we call "fat max" that affects the way your body burns fat from exercise that involves your maximum heart rate, which you can approximate by taking the number 220 minus your age.  So, since I'm 18, my maximum heart rate should be around 202.  Now, when your heart rate gets up this high, your body actually stops burning fat.  Let's use another hand-drawn gorgeous graph.

Excuse the bad handwriting, I don't have my tablet with me.

Basically, extremely strenuous exercise won't burn as much fat as moderate exercise.  Once you pass your fat max point, you start metabolizing glycogen from your liver (which is basically just stored glucose).  This glycogen is then restored once you eat more glucose.  The catch is to exercise while you're ketotic.  Since there is no glycogen in your liver for your body to burn, it has to get it from fat!

Now, onto ketoadaptation.  I mentioned before that I completely ran out of energy while I was exercising.  That was because I hadn't fully adjusted to ketosis yet.  After the day I had, I think I can say that I am pretty well adjusted to it now.

I said above that I hiked up Camelback, which I did.  Then, a few hours later, I had a three and a half hour belt exam for karate.  And it wasn't even a regular exam, oh no.  This was a make-up exam, which consisted of about twenty people.  Which means all the instructors are focused on you.  The whole time.

Always watching.  Smiling at your pain.

So that was fun.  The whole point of this is that, even though I thought I would completely run out of energy and not be able to finish my test after my crazy hike, I was able to push through without getting too tired.  This means that I have almost completely adapted to ketosis, so I should be seeing some of the more positive effects, like increased energy and endurance, soon, so that's something to look forward to!

And I did pass my test, so there's that too.

Next time, I promise I'll talk more about Malonyl-CoA and its role in fat burning.  Until then!

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!

Ketosis: Personal Thoughts

Sorry for the delay in posting, everyone!  I was going to post yesterday, but I spent a lot longer at Regionals than I thought I was going to.  And then all day today.  But that's over now, so you can expect a more consistent schedule from here on out.

I said last week that I was going to go into more detail about what ketosis actually is from a first-hand perspective.  But first, I'll repeat what ketosis is for those of you who aren't hanging onto my every word (shame on you).

Being in "ketosis" (or, being "ketotic") is the state your body is in when it is burning fat.  When your body runs out of glucose stores, it starts to burn fat for energy, producing chemical structures called ketones.  Any of you who have studied organic chemistry should remember what those are.  If you haven't, they look like this:

They smell like fruit or for some reason.

Each R is just another long chain of carbons, but that isn't really super important.  Ketones can pass through the blood-brain barrier to supply energy for the brain so that it still works right, since longer fatty acid chains are too big to really be useful in that area.  I'll get into how that works in a later post.  Afterwards, your body gets rid of the ketones through the urine.

I mentioned last time that there is a very useful way to test if you're ketotic.  Most drug stores sell test strips that turn purple when in the presence of ketones.  Since they are flushed out of the body through the urine, that's what you can test to see if you're ketotic.

Kind of gross, but it works.

As part of my project, I am going on a low-carb diet to induce ketosis so I can see the biochemical effects first hand.  As of Wednesday, I am officially ketotic, so I can share some of my thoughts about the experience.

First of all, this means I can't eat any carbs or sugar.  Well, I can eat up to 50 grams of carbs a day, and while this sounds like a lot, it helps to look at certain foods.  One slice of bread has 36g of carbs.  If I eat a sandwich, that uses more than my daily carb limit.

It's not just bread that has a huge amount of carbohydrates; any grains (including pasta, oatmeal, and cereals) contain a high amount of carbs.  Certain fruits, like pineapple and mango (all the really sweet ones, basically) have a high amount of fructose, which contains a molecule of glucose.

The silent killer.

Milk and most other dairy products contain a fairly high amount of carbohydrates as well.

So, what can someone on a diet like this eat?  Lots of vegetables, for one.  Green leafy vegetables are okay, but sweet veggies like carrots and parsnips aren't really that great for you (as, you guessed it, both have a high amount of carbs).  Protein is also important to eat--as you might remember from my last post, protein supplies the body with glucose through gluconeogenesis so that your body still works correctly.  Surprisingly, fats and oils are still okay to eat.

Here's a list of foods that are surprising that you can eat:
1. Eggs
2. Cheese (as long as it's hard cheese)
3. Steak
4. Strawberries (each only have around 1g of carbs per fruit)
And, my personal favorite,
5. Bacon

Any diet where this is okay to eat is fine in my book.

Here's a list of food that I'm surprised you can't eat:
1. As stated above, carrots
2. Hummus
3. Popcorn
4. Any type of bean
5. Peas, and legumes in general
6. Most fruits

I think the part that is the most difficult to deal with is the fact that you can't eat potatoes.  Potatoes are really starchy, which is pretty much pure carbohydrates.

But enough about what you can't eat.  How did it feel to start ketosis?  Basically, when I first started to burn through my stored glucose, I was pretty miserable.  I missed eating bread almost immediately, but it wasn't really difficult to actually do.  Breakfast seems be the toughest meal to deal with, since pretty much all you can eat are eggs and sausage.  I need to do a little more digging to find good breakfast recipes.  I'll definitely share them here if I find any.

Once I became ketotic though, it started to get weird.  I felt different than I would have if I had been eating carbs.  I can't really describe the sensation; it was almost like having a headache without it actually hurting, if that makes sense.  It was probably because I needed to drink more water.  I should probably mention that risk of dehydration increases somewhat when you're ketotic, since a lot of the water associated with glucose storage goes away.  So that's a thing.

I was very surprised at what foods I was craving, though.  I had expected to crave bread, because that's where most of my carbs were coming from before I started this project.  However, I just really, really wanted a piece of fruit.  The fruit cravings were driving me crazy.  I remembered that Dr. Walker had said that I should wait until I was ketotic and then experiment with different fruits to see if they bounced me out of ketosis.  So, purely for scientific reasons and totally not just because I needed a piece of fruit right now, I cautiously ate a kind of strawberry.  It was kind of wilty and soft in some places, and looked kind of icky.

It was the BEST STRAWBERRY I've ever had in my LIFE.

*Hallelujah Chorus plays joyfully in the background*

As it turns out, having an occasional strawberry doesn't kick me out of ketosis, so I can enjoy the occasional strawberry without it messing anything up.

My mom, who's also doing this with me because she doesn't want me to be alone (thanks, Mom!), has had some side effects that I haven't had.  She says that she has this constant bad taste in her mouth.  This is because ketones are also secreted through saliva, and they really don't taste very good.  You should be able to fix this by drinking more water and diluting your saliva.

She also seems to have increased irritability.  Ketosis apparently does this to some people, but I'm not sure why, so I'll be researching that and reporting what I find here.  This might not have anything to do with ketosis, since she's kind of grumpy anyway (love you, Mom!), but it probably does.

That about wraps it up for this post.  Next time I'll get more into the nitty gritty science of cellular metabolism in the mitochondria and what happens when there's an overload of glucose.  Until then, so long!

Getting Started

Hello, everyone!  I just started my project yesterday, which I am genuinely excited about—looking at biochemistry at work should prove to be very interesting.  Basically, the first thing Dr. Walker did was to give me his patented Crash Course in Everything Related to a Low-Carb and Low-Sugar Diet Plan™, which mostly consisted of him explaining how sugars are stored in the body while I sat with a slight deer-in-the-headlights look on my face (hey, it’s been a while since I studied metabolism in biology).  After the initial shock of the words “gluconeogenesis” and “triglyceride storage” wore off, I was actually very surprised to learn that what most people think makes you gain weight is actually completely wrong.

Here’s a question:  what is the most unhealthy thing a person can eat?  What will make a person gain the most weight?  I bet a lot of you said “fat.”  Fat contains a lot of calories, which makes you gain weight when you eat too much of them, right?  And there are a few types of fat, some of which you should avoid, and some of which you should try to eat more of, right?  Also, something about cholesterol.

Here’s my answer: foie gras.

Delicious, delicious foie gras.

What?  I can hear you say.  “Foie gras” doesn’t answer anything.  What a bizarre non sequitur.

Actually, no: the answer lies in how you make foie gras.  Foie gras is the liver of a duck or goose that has been specially fattened by force-feeding them huge amounts of food (placed under a link because the picture is absolutely horrible).  How do you make the liver store huge amounts of fat?  Corn.

Somewhere a duck is crying.

Corn has a lot of sugar.  When a person (or a duck) eats carbohydrates, that glucose is stored in what is called "ectopic fat," which basically means "fat where it doesn't really belong."  This includes areas like the liver (as is the case with foie gras), inside muscle tissue, and around the gut (like a beer belly). Because of ectopic fat within muscle tissue (probably the worst offender), cells' insulin receptors, which allow for the body to metabolize sugar, can become resistant to the presence of insulin.  And when there's excess insulin in your system, where does the sugar go to be stored? As more fat.

This insulin resistance places the body in a constant state of fat storage.  As carbs and sugars are eaten, excess sugars are then "bounced off of" ectopic fat, and the body simply stores it within fat cells.  So we can see that it's not fat that causes problems, it's sugar.

So what happens when you cut off your sugar and carbohydrate supply?  Your body needs glucose to function normally, both physically and mentally.  The thing is, your body can also break down fat to produce fatty acids (which provide energy) and ketones (which supply energy to the brain through the blood-brain barrier).  This process breaks down fat rather than storing it to provide energy because, while your body can turn sugars into fat, it can't turn fat back into sugar.

When you stop eating carbs, the only place your body can get its energy is from fat, and the first place it takes it from is the ectopic fat in your liver and muscle tissue.  The ketones resulting from these reactions are secreted from the body through urine--which is easily measurable through the use of a certain indicator, which turns bright purple, which is awesome.  This state--burning fat instead of storing fat--is called "ketosis."  Being ketotic has a variety of side effects, including losing weight (which is good, especially for type II diabetics), and a number of less pleasant symptoms, including such great things like bad breath, irritability, dehydration, and headaches.

There's more to the story, though.  How come this metabolism doesn't lead to extreme unhealthiness?  Not eating enough carbs can lead to anorexia, can't it?  The answer to this is Batman.  Or at least Christian Bale.

Note: Both of these are the same person.  Taken a year apart.

The one on the left is from The Machinist, while the one on the right is from the Dark Knight trilogy.  These movies are only a year apart, so why the huge change in his body?  Both diet regimens involved eating low amounts of carbohydrates and sugars.  So why does he look like a zombie in one picture and look really muscular in the other?  In the first movie, he ate very little protein, while in the second, he downed tons of protein in a very short amount of time.  This works because of one of those scary words I mentioned before: "gluconeogenesis."  This is the process the body uses to get glucose from other, non-carbohydrate sources in order to prevent hypoglycemia (which is when you don't have enough glucose in your bloodstream).

So, by eating a high amount of protein (which, yes, does include animal fats and oils) and a low amount of sugar and carbohydrates, your body enters a state of ketosis, where it burns fats instead of storing them, and creates glucose from protein, so you stay healthy instead of wasting away like zombie Christian Bale up there.

Later this week, I'll go into more detail on how to get into ketosis in the first place--diet, exercise plans, the works--and how it actually feels being on a low-carb diet, and hopefully ketotic by that point.