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 5th
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.
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