Fat Metabolism (Part 2)

Time for Fat metabolism:

                This section will focus on the complex processes of how a fatty acid is broken down, transported and used for energy in the cell. Again I will give you the main ideas rather than complicate the situation with big fancy biological names.

                First of all, fat cells, known as adipocytes and lipids, are large vacuoles of space and inside this space are triglycerides. This is a word most people have heard before but for many the actual meaning of the word is hazy. “Tri”- meaning three fatty acid chains attached to a glycerol back bone. These fatty acids are broken off the glycerol back bone and transported to where ever it needs to go. Let’s look at this incredible process more closely.

              

           Assuming our host is doing slow exercise or is in a fasted state, fat will be the main nutrient for producing energy. This is because glucose levels in the blood are low due to one of the above reasons unless you have a medical situation such as diabetes. Once the blood glucose levels are low then the body senses this with receptors in the arteries and sends a signal to the brain saying “Hey man we need more energy and we are out of glucose” . You may ask why do we not use the glucose from glycogen. We already have. The first signal of the brain is to use up glycogen stores in the muscle or liver. When these are out then the body has to go to its secondary nutrient, ie. fat. The hormone Epinephrine is send from the medulla of the Adrenal Glands, located on top of the kidneys. Some research shows that Glucagon can be used to activate this process as well because it is the starvation hormone. It is activated when the body does not have enough glucose. Other research shows that this is not the case and that inhibiting insulin, a hormone that takes up glucose out of the cell, is the source of this activation.

                When epinephrine binds to the outside of the cell it causes a signalling cascade which activates many different proteins along the way each passing a signal to the, eventually affected target. In this case our target is triglyceride. First epinephrine binds to Beta-Adrenergic Receptor, a protein imbedded into the phospholipid bilayer, also known as the cell membrane. This activates G protein which in turn activates  Adenylate Cyclase. After this step ATP is added to the process and bonds are broken to release energy inorder to keep the reaction moving forward. ATP turns into Cyclic AMP, which is a signalling molecule. This molecule activates Protein Kinase A. Here, another ATP is broken, but only once this time, to create a bit of energy and forming a molecule of ADP which is recycled for later use. Using this last ATP activates the Hormone Sensative Lipase which is the hormone that cuts off two of the fatty acids. Monoacylglycerol Lipase comes and finishes the job by cleaving off the last fatty acid chain. YAY, now we have 3 single fatty acids floating around and a glycerol back bone.

So what now? Well glycerol can have two fates depending on the situation. If the body is in a need for glycolysis such as during exercise, as mentioned above the glycerol back bone can be converted into Dihydroxyacitone Phosphate. (DHAP) This is where you guys suffer for not having me list off every molecule in glycolysis. DHAP is the 5^th step of glycolysis meaning that if we were to add more of these molecules then more substrates are available to fuel glycolysis WITHOUT GLUCOSE!!

The glycerol can also be used to create more triglycerides if need be. This may occur when a work out is finishing. The body does not need any more energy and maybe it broke down a few too many TGI’s and now has nowhere to put them. Time to recycle. This process takes a few more steps but inevitable ends up with a molecule of TGI.

So we have dealt with the glycerol and still have the fatty acids to deal with. The FA’s go to the cell membrane and diffuse through the membrane and attach to Albumin. Albumin is a carrier protein that attaches FA’s and transports them via the blood stream to a cell where they can be put into the mitochondria. Albumin is found in eggs as the white portion we see when we cook them. Intracellular carrier proteins grab the fatty acids and transport them into the cell once they reached the cell. Once in the cytoplasm of the cell outside of the mitochondria each fatty acid has to be “Activated” . This is done by adding a Coenzyme A onto carboxylic acid group. This is the side of the fatty acid that was attached to the glycerol backbone and consists of two oxygen’s and a hydrogen.

I guess we should take a minute a  describe a fatty acid. A fatty acid is known as a hydrocarbon chain. It consists of a carbon back bone with two hydrogen’s attached to each carbon.  This fatty acid is always moving around slightly and not fixed in an immoveable structure. This is important because it allows the cell membrane ( phospholipid bilayer) to move around and helps the cell function. It is like putting a human in a straight jacket. They do not have very good function and there is no way a mental patient deserving of this special treatment can be in the Olympics. We want all of our cells to be in the Olympics and to work at their greatest capacity. This is where bonds come into play. A fatty acid chain can either be straight with single bonds on every carbon known as a saturated fatty acid. This is bad for the cell to be made of too many of these for the above reason. The same fatty acid can have one or more double bonds and this causes the fatty acid to change shape and twist a bit and actually makes the fatty acid more moveable on the triglyceride and the cell membrane. The more moveable the fatty is the potentially better it is. These are known as Monounsaturated fatty acids or polyunsaturated fatty acids. Trans fats are a derivative of a polyunsaturated fatty acid where the double bond simply faces the opposite direction. This in a natural form is good for us but when influenced by heat or by pressure then it turns out bad for us and that is where the “trans fat” dogma came from. Companies do not naturally make food because chemicals and heat and pressure and other processes change the molecules for the worse. Omega 3 and 6 basically is a naming technique used by scientists to differentiate different fatty acids. “3” and 6” simply determine what carbon the first double bond is. Omega 3 is an essential fatty acid meaning it has to be ingested to get into our system. Too many Omega 6 fatty acids are said to compete for the same rate limiting enzymes as omega 3s and for this reason are said to be bad in large amounts.

Back to fat metabolism. While activating the fatty acid a thiol group, simply a sulfur molecule, is added to the fatty acid chain. This thiol group has a lot of energy and can be broken like an ATP to fuel reactions.  ATP is used to create this “activated” state of the fatty acid but that is a necessary consequence Now that the fatty acid is ready to go into the mitochondria. It diffuses through the outer membrane of the mitochondria but it has to be transported into the inner membrane with a carrier called Carnitine. The FA attaches to this molecule and rides in into the inner membrane of the mitochondria.  In the process of attaching to the Carnitine molecule the Coenzyme A is dropped and recycled.

Now it is time for Beta Oxidation once the fatty acid attached to the Caritine travels into the inner membrane.  Basically after a few steps the long fatty acid chain has shortened by two carbon molecules. This forms Acetyl  CoA. If you read the last article then you would know this is a substrate for the Kreb cycle which powers glucose metabolism. It is interesting how each process can aid other processes that seeming have nothing to do with each other.  In addition to Acetyl CoA  NAD and FAD is produced in these few reactions which can go into the ETC. Amazing  isn’t it.

If the Acetyl CoA’s do not go into the Kreb Cycle they will be converted into ketones in the liver.  This happens in small amounts normally and the keytones are reconverted into acetyl CoA’s  to be put back into different processes. In times of starvation keytones are used as an energy source in the brain and can cause a lot of harmful side effects.

Our Last Process is known as Lipogenesis and is the process of reversing the beta oxidation process we just discussed. Fatty acids are built up 2 carbons at a time in a multi step process that is not necessary to understand. The end result of this process is Palmitic Acid, a 16 carbon fatty acid with no double bonds. From this fatty acid many others are formed by groups of proteins that lengthen, shorten and create double bonds.  These are then transported to different parts of the body depending on their function.

 That is what happens to fat as it goes into the body. Last up is Protein. That will have to wait until a nother day however. 

Thanks :)