Cysteamine inhibition of [15N]-glycine turnover in cystinosis and of glycine cleavage system in vitro.
In order to clarify the hyperglycinemic effect of cysteamine treatment in children with nephropathic cystinosis, we measured [15N]-glycine turnover in three affected patients. Administration of cysteamine lowered the glycine flux and the glycine metabolic clearance rate but did not alter the glycine pool size. Formation of [15N]-serine from [15N]-glycine was lower in untreated patients than in control subjects and was reduced still further by cysteamine. Studies in vitro with isolated rat liver mitochondria and acetone extracts of mitochondria indicated that even low cysteamine concentrations (0.1 mM) inhibited the glycine cleavage system in both the direction of glycine oxidation and glycine synthesis. Cysteamine was a more potent inhibitor of the glycine cleavage system than any other sulfhydryl containing compound. Although no ill effects of cysteamine treatment were immediately apparent, patients receiving cysteamine should be monitored carefully for the appearance of any neurologic symptoms which might be referable to inhibition of the glycine cleavage system.
D003065:Coenzyme A / Q000502:physiology; D003543:Cysteamine / Q000494:pharmacology* / Q000502:physiology; D003554:Cystinosis / Q000378:metabolism*; D003653:Decarboxylation; D005998:Glycine / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008930:Mitochondria, Liver / Q000378:metabolism; D009587:Nitrogen Isotopes
D009587:Nitrogen Isotopes; D003543:Cysteamine; D003065:Coenzyme A; D005998:Glycine