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!