Leucine, the side chains of these give each

Leucine, Valine and Isoleucine are collectively
known as the branched-chain amino acids
(BCAAs), in which the side chains of these give each of the more than 20 amino
acids their unique characteristics. They have a similar
structure, but the side chains differ in the structural conformation and
hydrophobicity. For example, leucine is more common in a-helices, while valine
and isoleucine tend to be found in B-sheets. Together, the three branched-chain AAs make up approximately 33% of
all the AAs in the body. In fact, a great amount of these three AAs is found in
the skeletal muscle where they act as a structural element and store for
systemic nitrogen (Cole, 2015).

They are essential amino acids which means the
body cannot synthesize them, therefore,
must be obtained from the diet. A good source of these would be dairy products
and red meat. The BCAAs share enzymes that catabolise the first two steps in
their metabolism and are key amino acids in several systemic functions,
particularly nitrogen homeostasis and neurological function (Cole, 2015).

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The BCAAs first catabolic step does not occur in
the liver. They are degraded primarily in muscle tissue  since the liver lacks the aminotransferase enzyme
(Cole, 2015). Subsequently, their catabolism comprises two common steps and the
flux-generating step, branched-chain keto acid dehydrogenase (BCKD), is one of
them. (Brosnan & Brosnan, 2006).

 

 

 

 

 

 BCKD Complex

 The complex
consists of three catalytic subunits that utilises
five cofactors   (Burrage, et al., 2014):

·       Thiamine pyrophosphate (E1 component)

·       NAD+

·       FAD             
E3 component

·       Lipoate

·       CoA (E2 component)

The BCKD is produced by deamination of branched-chain amino acids valine, leucine and isoleucine.
Within its complex are found three enzymes, each of which has multiple copies.
These enzymes have been acknowledged as branched-chain
a-keto acid decarboxylase (E1), dihydrolipoamide acyltransferase (E2), and dihydrolipoamide
dehydrogenase (E3) (Brosnan & Brosnan, 2006). A genetic defect in this
complex has shown to be responsible for the Maple syrup urine disease which is
an autosomal recessive disease.

 

Cause-Genetics

Caused by a mutation in 1 of 4 genes that
comprise a protein complex which is responsible for the breakdown of AAs (leucine, isoleucine, valine).

     Three
genes that have been linked with MSUD are (Strauss, et al., 2006):

·       BCKDHA,
encoding BCKA decarboxylase (E1) alpha
subunit (MSUD type 1A)

·       BCKDH,
encoding BCKA decarboxylase (E1) beta
subunit (MSUD type 1B)

·       DBT,
encoding dehydrolipoyl transacylase (E2) subunit (MSUD type 2)

 

The aforementioned
genes are unique for the BCKD complex. E3 instead is involved in other complexes
and gives different phenotype characteristics.

If a person
has MSUD, this is due to either an absence or some type of defective branched-chain
a-ketoacid dehydrogenase which is caused by an elevation of a-keto acids and
branched- chain amino acids in the urine and blood. As these keto-acids accumulate,
they give the urine the odour of maple syrup.

Maple syrup
urine disease is inherited in an autosomal recessive manner which means that for
a person to have this disease they must inherit two defective traits, one from
the male parent and one from the female parent.