Mitochondrial Fatty Acid Oxidation Deficiencies.
In this lecture, I will start by describing
the biochemistry of mitochondrial fatty acid metabolism.
I will then talk about the fatty acid beta-oxidation deficiencies.
I will discuss the diagnostic strategies for their detection.
I will then use some time on the molecular genetics and molecular pathogenesis.
There after, I will mention the concept of
prevalent mutations and their use in the diagnostic procedure.
And finally, I will end up with some conclusions.
Now, let us look at the metabolites and enzymes of the fatty acid metabolism.
Fatty acids liberated from fat and foodstuff of
fatty foods are transported through the plasma membrane.
This transport is facilitated by the fatty acids transport protein.
The fatty acids are activated to the coenzyme-A derivative,
by means of fatty Acyl-CoA synthetase,
which is associated with the mitochondrial outer membrane.
To further metabolize the fatty acids, carnitine is necessary.
Carnitine is taken up through the carnitine transporter.
Carnitine is used as substrate to kill
the fatty Acyl-CoA for Carnitine palmitoyl-CoA transferase I.
The product is fatty Acyl carnitine,
which is located in the inter-membrane space of the mitochondria.
The fatty acyl carnitine is transported through
the inner-membrane and this is facilitated by carnitine/acylcarnitine translocase.
Now the fatty acids are inside the mitochondria but to be metabolized,
it has to be converted back to the acyl coenzyme-A derivative.