Familial hyperlysinemia with lysine-ketoglutarate reductase insufficiency.

Fibroblasts grown in tissue culture from the skin of normal subjects have lysine-ketoglutarate reductase activity (lysine: alpha-ketoglutarate: triphosphopyridine nucleotide (TPNH) oxidoreductase (epsilon-N-[L-glutaryl-2]-L-lysine forming)). The activity of the enzyme is considerably reduced in the skin fibroblasts grown from three siblings with hyperlysinemia. The high concentrations of lysine in the blood of these patients, the previous demonstration in the intact subject of a reduction in the ability to degrade lysine, and the present demonstration of diminished lysine-ketoglutarate reductase activity, accurately define the metabolic defect and establish the saccharopine (epsilon-N-[L-glutaryl-2]-L-lysine) pathway as the major degradative pathway for lysine in the human.