Lysine α-ketoglutarate reductase (LKR)

Lysine α-ketoglutarate reductase (LKR) is an oxidoreductase enzyme that catalyzes the first step of the saccharopine pathway of lysine degradation, where it condenses lysine and α-ketoglutarate to form saccharopine using NAD(P)H as a cofactor[2][5][7]. In animals and plants, LKR activity is typically mediated by a bifunctional enzyme complex that also provides saccharopine dehydrogenase (SDH) activity, encoded in humans by the *AASS* gene[3][5]. LKR is highly expressed in the liver but is also active in muscle, kidney, heart, and intestinal tissues in mammals[1][4]. Its activity is crucial for whole-body lysine balance, and impairment leads to hyperlysinemia and related metabolic disturbances[2][5]. LKR is not currently considered a major therapeutic target; however, its metabolic importance makes it a potential candidate for research in inherited metabolic disorders and possible future interventions in nutritional or metabolic diseases[2][5].

Other names

Lysine-ketoglutarate reductaseLysine α-oxoglutarate reductaseL-lysine-alpha-ketoglutarate reductaseLysine:alpha-ketoglutarate:TPNH oxidoreductaseLysine-2-oxoglutarate reductaseLysine:2-oxoglutarate reductase

Not targeted by current therapeutic drugs; potential experimental inhibition by substrate analogs or metabolic intermediates (e.g., saccharopine, α-aminoadipate, α-ketoadipate, various metals can inhibit activity in vitro)