Fats, fatty acids and fat metabolism
majority (95%) of the
fats in our food and also the fats stored in our body fat
triglyceride is made of one glycerol and 3 fatty acids.
Glycerol is some sort of sugar and is metabolised in the carbohydrate
fatty acid is made of 3
kinds of atoms: C (carbon), O (oxygen) and H (hydrogen). Fatty acids
have 4 to 24 carbon atoms. Depending on the number of carbons they are
called short chain fatty acids (C4 to C6), medium chain fatty acids (C6
to C12) and long or very long chain fatty acids (C12 and more).
of a fatty acid with 6 carbons (C6):
of a fatty acid with 16 carbons (C16):
acids can be burnt or oxidized in order to produce
oxidation of fatty
acids takes place in the mitochondria of the cell. A mitochondrion can
be seen as the energy factory of the cell.
Activation of a fatty acid
soon as a fatty acid arrives in the cell, it first has to be activated.
is done using a specific enzyme and the result is what we call an
acyl-CoA or acyl-coenzyme A. These acyl-CoA's have, just like the fatty
acid out of which they are made, a several number of carbon atoms.
Depending on the number of carbon atoms, we can speak of short chain,
medium chain, long chain or very long chain acyl-CoA's.
oxidation of the
acyl-CoA happens inside the mitochondria, so the activated fatty acids
first have to be transported through the membrane to the inside of the
Transport of the acyl-CoA
the shorter acyl-CoA's can pass the membrane of the
without any help. The longer acyl-CoA's
(as of C10) need the help of a substance called carnitine.
acyl-CoA will drop its CoA and replace it by a carnitine. The result is
an acylcarnitine that can be transported through the membrane of the
mitochondrion. Once the acylcarnitine is inside the mitochondrion the
carnitine is removed and replaced again by a CoA. The acyl-CoA is now
ready for being metabolised.
Metabolising of an acyl-CoA: beta-oxidation
biochemical process that happens in 4 steps. For each step a specific
enzyme is needed. Each time the end product of a certain step will be
used as the starting product for the next step.
enzyme needed for the first step is called acyl-CoA dehydrogenase.
There are 4 versions of this enzyme: one for short chain, medium chain,
long chain and very long chain fatty acids.
The enzyme necessary for the oxidation of medium-chain fatty acids is
then called medium-chain acyl-CoA dehydrogenase, or MCAD.
enzymes needed for the
3 other steps are not important with regard to MCAD deficiency
not further discussed in this text. But they are mentioned on the image
below that schematically represents the cycle of beta-oxidation:
end product of beta-oxidation after the 4th step is 1 acetyl-CoA and 1 acyl-CoA that is 2
carbon atoms shorter that the acyl-CoA that was started with. In this
process energy is released.
will be further processed by an other biochemical process (called the
citric acid cylce, Krebs cycle or TCA cycle). It can also be used to
produce ketones. See the pages on the fed-fast cycle for more information
that was also the result of the beta-oxidation, will undergo the
beta-oxidation process again. This cycle will continue until the fatty
acid is completely metabolized.
Medium-chain acyl-CoA dehydrogenase deficiency
deficiency is a deficiency (not properly
working) of an enzym
called acyl-CoA dehydrogenase necessary for the oxidation of medium
chain fatty acids. This enzyme is called the MCAD enzyme elsewhere on this website.
patients with MCAD deficiency the first step of beta-oxidation will not
work properly on medium chain fatty acids, and as a consequence also
the other steps of beta-oxidation will not work.
and very long chain
fatty acids will partially be oxidized until they become medium chain
fatty acids and will thus also need the MCAD enzyme.
Medium-chain acyl-CoA's are accumulated inside the mitochondrion because they cannot be further metabolised.
in times when the fat metabolism is accelerated (when fasting or in
case of illness with fever) the amount of acyl-CoA's can be very high
and this is toxic. It can cause serious complications.
Furthermore the body
count on oxidation of fatty acids for energy and depends on the intake
of sugar from food. In case of fasting or vomiting a lack of
energy can occur, and also this can have serious consequences.
Luckily these acyl-CoA's
don't have to be trapped inside the mitochondria for ever. The body
knows of ways to eliminate these substances, and one of the key players
more about carnitine >