Consequences of this mutation
A gene holds instructions or the "recipe" to
create a protein.
kind of proteins exist: antibodies, enzymes (used to carry out the
chemical processes in the body, such as fatty acid oxidation),
messengers, structural components and transport or storage proteins.
process to create a protein happens in 2 steps. The first step is
called transcription and copies the information stored in a gene's DNA
into a similar molecule called RNA. Ribosomes then read the information
in this RNA and use it to create proteins. This process is known as
translation; i.e., the ribosome "translates" the genetic information
from RNA into proteins.
A protein is a long chain of specific
building blocks called amino acids. The MCAD enzyme consists of 421 of
those amino acids in a very specific order. Some of these amino acids
attract each other, others repell each other.
|The long chain of amino acids will fold itself into a three dimensional structure. |
The image on the left is an example of what the MCAD enzyme looks like.
The three dimensional structure is very important for the functioning of the enzyme.
the enzyme is not correctly folded, then it won't work correctly. To
help enzymes in the folding process, other proteins are used. These
proteins are called chaperonins.
The protein made from the information on the ACADM gene is an enzyme. It is used in the fat metabolism (see also the pages on fat metabolism).
there is a mutation in the DNA of a gene (for example an A is replaced
by a G) then this means that also the protein that is made based on
this DNA will contain an error. In case of the A985G mutation on the
ACADM gene the produced enzyme will contain the so called K304E
mutation. This means that in the enzyme on position 304 the amino acid
K is replaced by an amino acid E, and that the enzyme does not
Many different mutations on the ACADM gene have been identified and cause MCAD deficiency.For most of these mutations the result is that the MCAD enzyme will not correctly fold and thus not correctly work.
some of these mutations the result is that the creation of the MCAD
enzyme is prematurely stopped, causing the enzyme to be too short
and not properly functioning.
of the mutated MCAD enzymes are also more thermosensitive than the
normal (or "wild type") MCAD enzyme. This means that they will more
quickly break down if the surrounding temperature rizes.
In case the temperature increases, the enzyme will (partially) unfold and will lose its three dimensional structure.
a normal MCAD enzyme will not breakdown below a temperature of 44,5 °C,
there are mutated enzymes that already break down at a temperature of
not even 40 °C.
Read futher about how the diagnosis
for MCAD deficiency can be made >