![]() It follows a recessive manner of inheritance. The maple syrup urine disease can be inherited between generations. valine, leucine and isoleucine degradation pathway in KEGG.component E3: dyhydroliponamide dehydrogenase ( DLD).component E2: dihydrolipoyl transacylase ( DBT).The component E1 has two polypeptide subunits: the α unit BCKDHA and the β unit BCKDHB. It catalyzes the decarboxylation of α-keto acids and triggers the activity of E2 subunit by means of catalyzing binding between E2 subunit and its cofactor. component E1: The E1 subunit is the branched-chain α-keto acid dehydrogenase.It has three component enzymes with different catalytic activities: The mitochondrial branched-chain α-keto acid dehydrogenase complex (BCKDC) is the main catalysator for the degradation of BCAAs in mitochondrial matrix. Also the energy metabolism is disturbed, since the accumulation of BCKAs interrupts the citric acid cycle.īranched-chain α-keto acid dehydrogenase complex the pH value of the blood decreases, which explains some of the symptoms described in Phenotype.īecause of the accumulation of leucine in the brain, other essential amino acids are displaced, which leads to depletion of important neurotransmitters like glutamate. Accumulation of BCKAs results in a ketoacidose, i. If the function of the enzyme complex BCKDC is disturbed like in MSUD, the amino acids and their metabolites (BCKAs) cannot be removed and accumulate in blood and tissue. ![]() Acetyl-CoA and Succinyl-CoA, which can participate in other metabolic pathways such as the citrate cycle. After a chain of reactions in mitochondria branched-chain α-keto acids will be transformed to derivatives of CoA, e.g. The produced α-keto acids are then transported into mitochondria and decarboxylated by the BCKDC. ![]() This process takes part in the cytosol of cells. This reaction is catalyzed by cytosolic branched-chain amino-acid aminotransferase which cuts off the α-amino group of the BCAAs and substitutes the chemical group with a carbonyl group. The first step in degradation of the BCAAs leucine, isoleucine and valine is the oxidation to branched chain α-keto acids (BCKAs). the pyruvate dehydrogenase complex.īCAA degradation (source: KEGG) highlighting disease associated enzymes The reason is that this subunit is also a part of other enzyme complexes, e. In some sources type III is actually considered another disease, which is similar to MSUD, called dihydroliponamide dehydrogenase deficiency. The serum levels of BCAAs can be normalized with a thiamine therapy, because in this form a mutation affects the affinity of a thiamine binding site of the BCKDC.Īll of the above mentioned forms can be caused by mutations in the gene of any subunit of the BCKDC.Īnother classification divides the disease into subtypes depending on the subunit of the enzyme complex (see Biochemical disease mechanism) that is altered - type IA/IB/II or III if subunit E1 (α chain), E1 (β chain), E2 or E3 is altered, respectively. In the thiamine-responsive form there is an enzyme activity of up to 40 %.A dietary restriction with low BCAA content can be an effective treatment. The intermittend form has a later onset, because there is only a partial enzyme activity.So the symptoms are less severe than in the classic form. In the intermediate form there is an enzyme activity of up to 30 %.The newborns develop severe symptoms 4 to 7 days after birth. ![]()
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