title: Extracorporeal enzyme reactors for depletion of phenylalanine in phenylketonuria.
abstract: Multitubular enzyme reactors with immobilized enzymes were developed to achieve depletion of circulating substrate by extracorporeal means. To act as prototypes, reactors were prepared with immobilized L-phenylalanine ammonia-lyase, an enzyme that metabolizes phenylalanine to trans-cinnamic acid and ammonia without the need for a coenzyme. We report the first application of phenylalanine ammonia-lyase reactors in an extracorporeal circulation system in a patient with phenylketonuria. A phenylalanine level of 1.82 mmol/L (for the last 6 years) decreased to 1.24 mmol/L after 5.5. hours of treatment, without the enzyme entering the circulation. Total phenylalanine depletion from blood and tissue stores was estimated at 1800 mg. The hemodialysis-like procedure proved to be without side effects, specific for phenylalanine, and suitable in the management of pregnant women with phenylketonuria and late-onset hyperphenylalaninemia. The extracorporeal use of enzyme reactors for temporary enzyme replacement represents a new, safe, and effective therapeutic modality.
mesh_terms: D000328:Adult; D000642:Ammonia-Lyases; D004800:Enzymes, Immobilized; D006801:Humans; D008297:Male; D010649:Phenylalanine / Q000097:blood*; D010650:Phenylalanine Ammonia-Lyase; D010661:Phenylketonurias / Q000097:blood / Q000178:diet therapy / Q000628:therapy*; D006435:Renal Dialysis
chemical_list: D004800:Enzymes, Immobilized; D010649:Phenylalanine; D000642:Ammonia-Lyases; D010650:Phenylalanine Ammonia-Lyase