Regulation of galactose metabolism: implications for therapy.
In view of evidence that dietary therapy of galactose-1-phosphate uridyltransferase deficiency has failed to prevent complications of the disorder, there is a need for new strategies in treatment. The enhancement of residual enzyme activity in tissues of galactosaemic patients should provide such an approach. This possibility is derived from knowledge of the regulation of transferase activity in normal animal tissues. The pertinent observations summarized herein are: (1) that hepatic transferase activity is modulated by various cellular metabolites, uridine nucleotides being of particular significance; (2) that transferase activity in the young rat liver is subject to developmental programming with a several-fold increase after birth; (3) that transferase activity in pregnant rat liver is significantly increased which may be related to hormonal effects of progesterone; and (4) that pharmacological doses of folic acid may increase transferase activity. The basis of such regulation can give insight into sufficient augmentation of the residual activity to increase galactose utilization and thereby better the long-term outcome.
Segal
S
S
Division of Biochemical Development and Molecular Diseases, Children's Hospital of Philadelphia, Pennsylvania.
Rogers
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S
D000818:Animals; D005492:Folic Acid / Q000627:therapeutic use*; D005693:Galactosemias / Q000178:diet therapy / Q000201:enzymology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D011374:Progesterone / Q000494:pharmacology; D005694:UTP-Hexose-1-Phosphate Uridylyltransferase / Q000172:deficiency*
D011374:Progesterone; D005492:Folic Acid; D005694:UTP-Hexose-1-Phosphate Uridylyltransferase