Dehydrogenase E1 and transketolase domain-containing protein 1 (DHTKD1)

Dehydrogenase E1 and transketolase domain-containing protein 1 (DHTKD1) is a mitochondrial enzyme that operates as the E1 component of the 2-oxoadipate dehydrogenase complex (OADHC), playing a critical role in the catabolism of several amino acids, including lysine, hydroxylysine, and tryptophan[1][2][5][6]. It catalyzes the decarboxylation of 2-oxoadipate to glutaryl-CoA, constituting a key step in mitochondrial energy metabolism[2][5]. DHTKD1 forms a homodimer and operates in conjunction with shared E2 (DLST) and E3 (DLD) subunits, similar to components of the 2-oxoglutarate dehydrogenase complex[2][4]. Defects in DHTKD1 are associated with rare metabolic disorders, notably 2-aminoadipic 2-oxoadipic aciduria, and with Charcot-Marie-Tooth disease type 2Q[1][2][5]. Genetic and functional studies further implicate altered DHTKD1 activity in type 2 diabetes and other cardiometabolic diseases, where impaired mitochondrial respiration, reduced ATP generation, and altered reactive oxygen species production are observed[3]. Experimental inhibitors of DHTKD1, such as adipoylphosphonic acid and tenatoprazole, provide tools for probing function but highlight the need for careful monitoring given the enzyme’s essential role in energy balance and neurometabolic health[2][5].

Other names

2-oxoadipate dehydrogenase complex component E1E1aOADC-E1OADH-E1Alpha-KADH-E1KIAA1630MGC3090DKFZP762M115CMT2QAAKADAMOXADprobable 2-oxoglutarate dehydrogenase E1 component DHKTD1, mitochondrialalpha-ketoadipate dehydrogenase

Competitive or allosteric inhibition of the E1 component of the 2-oxoadipate dehydrogenase complex, impairing catabolism of 2-oxoadipate and downstream metabolic pathways