Characterization of a Human Dihydrolipoamide Dehydrogenase Mutant Showing Significantly Decreased Catalytic Efficiency toward NAD +

Journal of the Korean Chemical Society

article

Hakjung Kim¹ 

[1] Department of Chemistry, College of Natural and Life Sciences, Daegu University

关键词: Dihydrolipoamide dehydrogenase;    Pyridine nucleotide-disulfide oxidoreductase;    Flavoenzyme;   

DOI  :  10.5012/jkcs.2020.64.3.141

学科分类：化学（综合）

来源: Korean Chemical Society

【 摘 要 】

Dihydrolipoamide dehydrogenase (E3) (dihydrolipoamide: NAD+ oxidoreductase; EC 1.8.1.4) is a flavin-dependent homodimeric enzyme containing one FAD as a prosthetic group at each subunit (Fig. 1).1 Each subunit of human E3 is composed of 474 amino acids with a molecular mass of 50,216 daltons.2 Three a-keto acid dehydrogenase complexes (pyruvate, a-ketoglutarate and branched-chain aketo acid dehydrogenase complexes) have E3 as a common component.3 E3 catalyzes the reoxidation of the dihydrolipoyl prosthetic group attached to the lysyl residue(s) of the acyltransferase components of the three a-keto acid dehydrogenase complexes. Because E3 is an essential component in three a-keto acid dehydrogenase, the decrease of E3 activity can affect the activities of all three complexes. This results in increased urinary excretion of a-keto acids, elevated blood lactate, pyruvate, and branched chain amino acids. Patients with an E3 deficiency normally die young because such a deficiency is a detrimental genetic defect that harms the central nervous system. Leigh syndrome with recurrent episodes of hypoglycemia and ataxia, permanent lactic acidaemia and mental retardation can be manifested.

【 授权许可】

Unknown