Homocystinuria: Observations on the biosynthesis of cystathionine and homolanthionine

Gerald E. Gauli, Yoshiro Wada, Karmela Schneidman, David K. Rassin, Harris H. Tallan, John A. Sturman

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12 Scopus citations


Patients with homocystinuria and a normal subject excreted cystathionine (1.8-15.0 μmoles/hr) after oral administration of homoserine plus cysteine; administration of both precursors is necessary. Excretion in the urine of the next higher homologue of cystathionine, homolanthionine, was found to occur spontaneously (0.8—1.5 μmoles/ hr), but not constantly, in three of seven patients with homocystinuria; loading with homoserine increased homolanthioninuria (2.9-5.7 μmoles/hr). Optimum conditions were established in crude extracts of rat liver for in vitro synthesis of cystathionine from homoserine and cysteine (reverse cystathionase) and of homolanthionine from homoserine and homocysteine. Under these conditions, a greater capacity for synthesis of cystathionine by reverse cystathionase (1856 m μmoles/ mg protein/hr ± 95) than for its cleavage in the forward direction (951 mμmoles/mg protein/hr ± 26) was demonstrated in liver; brain showed barely measurable activity in either direction. In crude extracts of livers from two patients with homocystinuria, activity of reverse cystathionase (39 and 56 mμmoles/mg protein/hr) was less than cleavage (144 and 396 m μmoles/mg protein hr), and both activities were far less than that found in rat liver extracts under the same conditions. Homolanthionine synthesis in rat brain was almost nil; in the other rat organs, it was far less than cystathionine synthesis by reverse cystathionase (compare 69 m μmoles/mg protein/hr ± 2 in rat liver); it was greater in extracts of rat liver than in extracts of human liver (6.7-10.8 mμmoles/mg protein/hr in human liver); it was virtually absent from the liver of the vitamin B6-deficient rat, but activity was restored by pyridoxal phosphate added in vitro. Homolanthionine synthesis activity in rat liver was separated from cystathionine synthase by ammonium sulfate fractionation (Table IX); it was not separated from cystathionase by such fractionation or by chromatography on carboxymethylcellulose (Fig. 3).

Original languageEnglish (US)
Pages (from-to)265-273
Number of pages9
JournalPediatric Research
Issue number6
StatePublished - Jun 1971
Externally publishedYes

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health


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