Enzyme studies in a patient with saccharopinuria: a defect of lysine metabolism.

Abstract

Extract: Elevated levels of saecharopine, lysine, and citrulline in urine and plasma were observed in a patient suffering from saccharopinuria. Using radioisotope methods the lysine-degradative enzymes, lysine-oxoglutarate reductase and saecharopine dehyrogenase, were studied in skin fibroblasts grown from this patient and from healthy subjects. The results show that, in contrast to healthy individuals (range 177–320 pmol formed/min/mg protein), the paitent's fibroblasts are completely lacking in saecharopine dehydrogenase activity, which accounts for the presence of the high levels of saccharopine. The patient also has a reduced level of lysine-oxoglutarate reductase activity (333 pmol saccharopine formed/min/mg protein; range 550–1,570 nmol), which may in part explain the hyperlysinemia. A further enzyme saecharopine oxidoreductase which metabolizes saecharopine to lysine was found to be present in the patient's fibroblasts (63 pmol lysine formed/min/mg protein) but absent from those of healthy control subjects. This indicated induction of this enzyme by the patient in an attempt to reduce the high levels of saecharopine in her tissues and body fluid. Speculation: There are two interesting features of this patient with saccharopinuria which the present studies have not clearly defined, namely the presence of high levels of lysine and citrulline found in plasma and urine. There are three possible explanations for the hyperlysinemia which may be operating singly or in combination. Depression in activity of lysine-oxoglutarate reductase (the patient possesses 37% of the normal activity). Inhibitory effect of saecharopine on lysine-oxoglutarate reductase (in vitro studies). Induction by the patient of saccharopine oxidoreductase which metabolizes saccharopine to lysine. No explanation has yet been found for the high levels of citrulline in plasma and urine.