Leucine, Valine and Isoleucine are collectivelyknown as the branched-chain amino acids(BCAAs), in which the side chains of these give each of the more than 20 aminoacids their unique characteristics. They have a similarstructure, but the side chains differ in the structural conformation andhydrophobicity. For example, leucine is more common in a-helices, while valineand isoleucine tend to be found in B-sheets. Together, the three branched-chain AAs make up approximately 33% ofall the AAs in the body. In fact, a great amount of these three AAs is found inthe skeletal muscle where they act as a structural element and store forsystemic nitrogen (Cole, 2015).They are essential amino acids which means thebody cannot synthesize them, therefore,must be obtained from the diet. A good source of these would be dairy productsand red meat.
The BCAAs share enzymes that catabolise the first two steps intheir metabolism and are key amino acids in several systemic functions,particularly nitrogen homeostasis and neurological function (Cole, 2015).The BCAAs first catabolic step does not occur inthe 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 theflux-generating step, branched-chain keto acid dehydrogenase (BCKD), is one ofthem.
(Brosnan & Brosnan, 2006). BCKD Complex The complexconsists of three catalytic subunits that utilisesfive 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-chaina-keto acid decarboxylase (E1), dihydrolipoamide acyltransferase (E2), and dihydrolipoamidedehydrogenase (E3) (Brosnan & Brosnan, 2006). A genetic defect in thiscomplex has shown to be responsible for the Maple syrup urine disease which isan autosomal recessive disease. Cause-GeneticsCaused by a mutation in 1 of 4 genes thatcomprise a protein complex which is responsible for the breakdown of AAs (leucine, isoleucine, valine).
Threegenes that have been linked with MSUD are (Strauss, et al., 2006):· BCKDHA,encoding BCKA decarboxylase (E1) alphasubunit (MSUD type 1A)· BCKDH,encoding BCKA decarboxylase (E1) betasubunit (MSUD type 1B)· DBT,encoding dehydrolipoyl transacylase (E2) subunit (MSUD type 2) The aforementionedgenes are unique for the BCKD complex. E3 instead is involved in other complexesand gives different phenotype characteristics.If a personhas MSUD, this is due to either an absence or some type of defective branched-chaina-ketoacid dehydrogenase which is caused by an elevation of a-keto acids andbranched- chain amino acids in the urine and blood. As these keto-acids accumulate,they give the urine the odour of maple syrup.
Maple syrupurine disease is inherited in an autosomal recessive manner which means that fora person to have this disease they must inherit two defective traits, one fromthe male parent and one from the female parent.