A UDP-sugar pyrophosphatase is developmentally regulated in the rat retina.

Rat retina tissue contains relatively high amounts of GD3 in relation to ganglio-series gangliosides even in the adult stages. This was attributed in part to an activity ratio between the enzyme that converts GM3 to GD3 [sialytransferase II (ST-II)] and the enzyme that converts GM3 to GM2 [N-acetylgalactosaminyltransferase (GalNAc-T)] favorable to ST-II. Here we report the presence in the rat retina tissue of an activity that hydrolyzes one of the substrates of GalNAc-T, the donor sugar nucleotide UDP-GalNAc. Chromatographic analyses of the products of degradation indicate that the activity corresponds to a UDP-sugar pyrophosphatase/phosphodiesterase I. The activity is developmentally regulated, increasing after day 4 of postnatal development to reach values approximately 10-fold higher in the adult tissue. The activity sediments with the microsomal membranes, also hydrolyzes UDP-Gal, does not hydrolyze CMP-NeuNAc, requires Mn2+, and does not require detergent. Kinetic data showed that the same activity hydrolyzes UDP-GalNAc and UDP-Gal, each one acting as competitive inhibitor for the hydrolysis of the other (Km and Ki for UDP-GalNAc, 48 and 33 microM, respectively; Km and Ki for UDP-Gal, 5 and 12 microM, respectively). In another set of experiments, it was found that the activities of the GalNAc-T and the enzyme that converts GM2 to GM1 [galactosyltransferase II (Gal T-II)] increased about threefold from birth to day 4 and then decreased to stabilize by day 6 in values that were similar to those at birth and about one-half those of ST-II.(ABSTRACT TRUNCATED AT 250 WORDS)