Pyruvate dehydrogenase multienzyme complex (PDC) catalyzes the oxidative decarboxylation of pyruvate and the subsequent acetylation of coenzyme A to acetyl-CoA. The E1 component of PDC catalyzes the first step of the multistep process, using thiamine pyrophosphate (TPP) and a divalent cation as cofactors. E. coli PDC is a homodimeric enzyme [].
In prokaryotes and eukaryotes, pyruvate dehydrogenase complex (PDC) contains multiple copies of three enzymatic components: pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2) and lipoamide dehydrogenase (E3) []. PDC catalyses the overall conversion of pyruvate to acetyl-CoA and CO2. In eukaryotes, PDC is located in the mitochondrial matrix [, ]. This entry represents agroup of E3-binding proteins, including dihydrolipoamide acetyltransferase (E2) and pyruvate dehydrogenase protein X component (known as Pdx1). Pdx1, found only in eukaryotes, plays a structural role in the complex by binding and positioning dihydrolipoamide dehydrogenase (E3) to the dihydrolipoamide acetyltransferase (E2) core []. Mutations in the Pdx1 gene has been linked to human disease [, ]. Mutations in the E2 gene cause pyruvate dehydrogenase deficiency [].
The 2-oxo acid dehydrogenase multienzyme complexes []from bacterial andeukaryotic sources catalyze the oxidative decarboxylation of 2-oxo acids tothe corresponding acyl-CoA. These include: Pyruvate dehydrogenase complex (PDC). 2-oxoglutarate dehydrogenase complex (OGDC). Branched-chain 2-oxo acid dehydrogenase complex (BCOADC). These three complexes share a common architecture: they are composed ofmultiple copies of three component enzymes - E1, E2 and E3. E1 is a thiaminepyrophosphate-dependent 2-oxo acid dehydrogenase, E2 a dihydrolipamideacyltransferase, and E3 an FAD-containing dihydrolipamide dehydrogenase. E2 acyltransferases have an essential cofactor, lipoic acid, which iscovalently bound via a amide linkage to a lysine group. The E2 components ofOGCD and BCOACD bind a single lipoyl group, while those of PDC bind either one(in yeast and in Bacillus), two (in mammals), or three (in Azotobacter and inEscherichia coli) lipoyl groups []. In addition to the E2 components of the three enzymatic complexes describedabove, a lipoic acid cofactor is also found in the following proteins: H-protein of the glycine cleavage system (GCS) []. GCS is a multienzymecomplex of four protein components, which catalyzes the degradation ofglycine. H protein shuttles the methylamine group of glycine from the Pprotein to the T protein. H-protein from either prokaryotes or eukaryotesbinds a single lipoic group. Mammalian and yeast pyruvate dehydrogenase complexes differ from that ofother sources, in that they contain, in small amounts, a protein of unknownfunction - designated protein X or component X. Its sequence is closelyrelated to that of E2 subunits and seems to bind a lipoic group []. Fast migrating protein (FMP) (gene acoC) from Ralstonia eutropha (Alcaligenes eutrophus) [].This protein is most probably a dihydrolipamide acyltransferase involved inacetoin metabolism. This signature contains the lipoyl-binding lysine residue. The domain surronding this site is evolutionary related to that around the biotin-binding lysine residue of biotin requiring enzymes.
