The biosynthesis of cystathionine in patients with homocystinuria.

Abstract

Top of pageAbstract Extract: The synthesis in rat and normal human liver homogenates of cystathionine from homoserine+cysteine was studied. When cystathionine was used as substrate, cyst(e)ine was formed and incubation of liver homogenate with homoserine+cysteine resulted in the formation of cystathionine. Incubation of homogenate prepared from homocystinuric liver with L-homoserine+DL-cysteine-3-14C or DL-cysteine-35S resulted in the formation of labelled cystathionine. The identity of cystathionine was established in three chromatographic separations. Oral loading with homoserine and cysteine or cystine in two patients with homocystinuria resulted in urinary excretion of cystathionine in amounts similar to that reported in normal human subjects without amino acid loading. Speculation: The observation that human and monkey brains contain much larger quantities of cystathionine than those of other species [26] suggests a special relation of this amino acid to the normal development and function of the primate brain. Cystathionine is either absent from or markedly deficient in the brain of untreated homocystinuric patients [2, 9]. Since we have shown that synthesis of cystathionine from homoserine and cysteine does take place in the patient's liver in vitro, supplementation of the diet with homoserine and cysteine may prove effective in raising intracellular cystathionine concentration toward the normal, and may possibly improve the prognosis in this disease. Keywords: Cystathionase; cystathionine; cystine; homocystinuria; homoserine; pyridoxine; serine