The oxidation of C 14galactose by patients with congenital galactosemia : Evidence for a direct oxidative pathway

Abstract

The oxidation of galactose-1-C 14 and galactose-2-C 14 by normal human subjects and patients with congenital galactosemia who lack the enzyme, galactose-1-phosphate uridyl transferase, was measured to determine whether this newly described direct oxidative pathway of galactose metabolism was present. Via this route, galactose is oxidized to galactonate which is subsequently decarboxylated to form d-xylulose, a keto sugar capable of entering the pentose phosphate metabolic pathway. By comparing C 14O 2 excretory pattern after intravenous administration of galactose-1-C 14 and galactose-2-C 14 with those seen after giving glucose correspondingly labeled, it was concluded that normal man oxidizes both small and large amounts of intravenously administered galactose to carbon dioxide by conversion first to glucose via the well known uridine sugar nucleotide pathway. On the other hand, in the Caucasian galactosemic subject with little capacity to oxidize galactose twice as much label is incorporated into carbon dioxide after giving galactose-1-C 14 than when galactose-2-C 14 is given, a finding consistent with operation of the oxidative route. The Negro variant galactosemic subject who can metabolize galactose demonstrates patterns of C 14O 2 formation similar to the normal. The data indicate that the low residual oxidative activity in the Caucasian galactosemic patients is due to operation of the galactonate pathway. The unknown metabolic pathway for extensive galactose oxidation in the Negro galactosemic subject is probably more closely related to one in which there is no differential oxidation of carbon one of galactose, like the conventional sugar nucleotide pathway.