Multiple enzyme defects in familial hyperlysinemia.

Abstract

Lysine-ketoglutarate reductase (EC. 1.5.1.8) deficiency in skin fibroblasts has been previously reported in patients with familial hyperlysinemia, providing an adequate explanation for the biochemical derangements noted clinically. In the present study, analysis of liver obtained at autopsy from a patient with familial hyperlysinemia confirmed the lysine-ketoglutarate reductase deficiency but, unexpectedly, also revealed an absence of saccharopine dehydrogenase (EC. 1.5.1.9) and saccharopine oxidoreductase activity. Skin fibroblasts from two siblings with the disease and a third patient from an unrelated family were also deficient in all three enzymes (lysine-ketoglutarate reductase, average 9%; saccharopine dehydrogenase, average 4%; saccharopine oxidoreductase, less than 10% of normal). The possibility that saccharopine dehydrogenase is a substrate-inducible enzyme was investigated by maintaining normal skin fibroblasts in a medium with minimal lysine concentration, and exposing hyperlysinemic fibroblasts to elevated saccharopine concentrations. There was no significant modification in saccharopine dehydrogenase activity.

• Authors: J Dancis, J Hutzler, N C Woody, R P Cox
• Journal: Pediatric research (Pediatr Res) Vol. 10 Issue 7 Pg. 686-91 (Jul 1976) ISSN: 0031-3998 [Print] United States
• PMID: 934735 (Publication Type: Journal Article)

Chemical References

• Oxidoreductases Acting on CH-NH Group Donors
• Saccharopine Dehydrogenases
• Lysine

Topics

• Adolescent
• Amino Acid Metabolism, Inborn Errors (enzymology, genetics)
• Child
• Fibroblasts (enzymology)
• Humans
• Liver (enzymology)
• Lysine (blood)
• Oxidoreductases Acting on CH-NH Group Donors (deficiency)
• Saccharopine Dehydrogenases (deficiency)
• Skin (enzymology)