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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Modulation of rat tissue galactose-1-phosphate uridyltransferase by uridine and uridine triphosphate.

Uridine-containing sugar nucleotides, uridine diphosphate (UDP)-glucose and UDPgalactose are important intermediates in galactose metabolism, and tissue UDPgalactose may be a salient factor in the etiology of the long-term clinical manifestations of patients with galactose-1-phosphate uridyltransferase deficient galactosemia. Because uridine and uridine nucleotides such as uridine triphosphate (UTP) are known inhibitors of rat hepatic transferase, we have examined the effects of these compounds on the activity of the enzyme in homogenates of rat brain and ovary which are target organs of galactose toxicity in classical galactosemia. In addition, the concerted effect of uridine and UTP together on hepatic transferase has been assessed. These investigations have been prompted by considerations that uridine administration may have a therapeutic role in the long-term treatment of classical galactosemia. Both uridine and UTP have been found to be potent inhibitors of brain and ovarian transferase activity. Brain enzyme activity is more sensitive to these compounds than is that of the ovary. They are competitive inhibitors of UDPglucose in both newborn and adult brain enzyme preparations with a ki of 0.15 to 0.20 mM. Uridine and UTP at low concentrations were found to have an additive effect on rat hepatic transferase activity, which is especially significant in that uridine administration is known to increase hepatic UTP concentration. These findings suggest judicious caution should be used in giving uridine to patients with genetically limited transferase activity because the possibility exists of inhibiting small amounts of residual enzyme in the tissues of affected subjects.[1]

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