Тарамдалған тізбекті α-кетоқышқыл дегидрогеназа кешені

Protein complex
The branched chain α ketoacid dehydrogenase complex (BCKDC or BCKDH complex) is a multi subunit complex of enzymes that is found on the mitochondrial inner membrane. This enzyme complex catalyzes the oxidative decarboxylation of branched, short chain alpha ketoacids. BCKDC is a member of the mitochondrial α ketoacid dehydrogenase complex family, which also includes pyruvate dehydrogenase and alpha ketoglutarate dehydrogenase, key enzymes that function in the Krebs cycle.

In animal tissue, BCKDC catalyzes an irreversible step in the catabolism of the branched chain amino acids L isoleucine, L valine, and L leucine, acting on their deaminated derivatives (L alpha keto beta methylvalerate, alpha ketoisovalerate, and alpha ketoisocaproate, respectively) and converting them to α Methylbutyryl CoA, Isobutyryl CoA and Isovaleryl CoA respectively. In bacteria, this enzyme participates in the synthesis of branched, long chain fatty acids. In plants, this enzyme is involved in the synthesis of branched, long chain hydrocarbons. The overall catabolic reaction catalyzed by the BCKDC is shown in Figure 1.

E1 uses thiamine pyrophosphate (TPP) as a catalytic cofactor. E1 catalyzes both the decarboxylation of the α ketoacid and the subsequent reductive acylation of the lipoyl moiety (another catalytic cofactor) that is covalently bound to E2.

E2 catalyzes a transfer of the acyl group from the lipoyl moiety to coenzyme A (a stoichiometric cofactor).

The E3 component is a flavoprotein, and it re oxidizes the reduced lipoyl sulfur residues of E2 using FAD (a catalytic cofactor) as the oxidant. FAD then transfers these protons and electrons to NAD+ (a stoichiometric cofactor) to complete the reaction cycle.

A deficiency in any of the enzymes of this complex as well as an inhibition of the complex as a whole leads to a buildup of branched chain amino acids and their harmful derivatives in the body. These accumulations lend a sweet smell to bodily excretions (such as ear wax and urine), leading to a pathology known as maple syrup urine disease. This enzyme is an autoantigen recognized in primary biliary cirrhosis, a form of acute liver failure. These antibodies appear to recognize oxidized protein that has resulted from inflammatory immune responses. Some of these inflammatory responses are explained by gluten sensitivity. Other mitochondrial autoantigens
include pyruvate dehydrogenase and branched chain oxoglutarate dehydrogenase, which are antigens recognized by anti mitochondrial antibodies. Mutations of the BCKDK gene, whose protein product controls the activity of the complex, may result in over activation of the complex and excessive catabolism of the three amino acids. This leads to branched chain keto acid dehydrogenase kinase deficiency, a rare disease first described in humans in 2012.