Dihydrolipoamide dehydrogenase: Functional similarities and divergent evolution of the pyridine nucleotide-disulfide oxidoreductases

Abstract

Dihydrolipoamide dehydrogenase (E 3) is the common component of the three α-ketoacid dehydrogenase complexes oxidizing pyruvate, α-ketoglutarate, and the branched-chain α-ketoacids. E 3 also participates in the glycine cleavage system. E 3 belongs to the enzyme family called pyridine nucleotide-disulfide oxidoreductases, catalyzing the electron transfer between pyridine nucleotides and disulfide compounds. This review summarizes the information available for E 3 from a variety of species, from a halophilic archaebacterium which has E 3 but no α-ketoacid dehydrogenase complexes, to mammalian species. Evidence is reviewed for the existance of two E 3 isozymes (one for pyruvate dehydrogenase complex and α-ketoglutarate dehydrogenase complex and the other for branched-chain α-ketoacid dehydrogenase complex) in Pseudomonas species and for possible mammalian isozymes of E 3, one associated with the three α-ketoacid dehydrogenase complexes and one for the glycine cleavage system. The comparison of the complete amino acid sequences of E 3 from Escherichia coli, yeast, pig, and human shows considerable homologies of certain amino acid residues or short stretches of sequences, especially in the specific catalytic and structural domains. Similar homology is found with the limited available amino acid sequence information on E 3 from several other species. Sequence comparison is also presented for other member flavoproteins [e.g., glutathione reductase and mercury(II) reductase] of the pyridine nucleotide-disulfide oxidoreductase family. Based on the known tertiary structure of human glutathione reductase it may be possible to predict the domain structures of E 3. Additionally, the sequence information may help to better understand a divergent evolutionary relationship among these flavoproteins in different species.