Homocystinuria: Biosynthesis of Cystathionine and Homolanthionine

Cystathioninuria after administration of homoserine and cystein has been confirmed in patients with homocystinuria; both precursors are necessary. Homolanthioninuria has been found to occur spontaneously in two of seven patients with homocystinuria and after homoserine loading in two more. A greater capacity for synthesis of cystathionine from homoserine and cysteine (reverse cystathionase) than for its cleavage (forward cystathionase) was demonstrated in rat liver, kidney and pancreas; rat brain showed very low activity in either direction. Homolanthionine synthesis from homoserine and homocysteine was less than 5% of cystathionine synthesis by reverse cystathionase in rat liver, kidney and pancreas; rat brain showed no activity. In liver extracts from two patients was less than cleavage and both were far less than in rat liver; homolanthionine synthesis activity in rat liver was separated from cystathionine synthase by ammonium sulfate fractionation; it was not separated from cystathionase by such fractionation or by chromatography on carboxymethyl-cellulose. Thus: (1) Although the administration of homoserine and cysteine results in cystathioninuria it is unlikely to promote formation of any considerable amount of cystathionine in the brain. (2) Whatever the excretion of homolanthionine may have to do with the pathogenesis of homocystinuria, it seems unlikely to have anything to do with the dementia. (3) Cystathionase, acting in the reverse direction is probably responsible for the synthesis of homolanthionine.