A UDP-Sugar Pyrophosphatase Is Developmentally Regulated in the Rat Retina

Authors

  • J. A. Martina,

    Corresponding author
    1. Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC), UNC-CONICET, Departamento de Química Biológica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, Córdoba, Argentina
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  • J. L. Daniotti,

    1. Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC), UNC-CONICET, Departamento de Química Biológica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, Córdoba, Argentina
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  • H. J. F. Maccioni

    1. Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC), UNC-CONICET, Departamento de Química Biológica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, Córdoba, Argentina
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  • This article is dedicated to the memory of Dr. Federico A. Cumar, who died on March 16, 1994.

Address correspondence and reprint requests to Dr. J. A. Martina at Departamento de Química Biológica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, CC 61 - (5016) Córdoba, Argentina.

Abstract

Abstract: 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 [sialyltransferase 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 ∼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 µM, respectively; Km and Ki for UDP-Gal, 5 and 12 µM, 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. Thus, at late stages the low activities of GalNAc-T and Gal T-II relative to ST-II and the high activity of the UDP-sugar nucleotide pyrophosphatase that would limit the availability of the UDP-GalNAc and UDP-Gal for GM2 and GM1 synthesis would be concurrent factors leading to the low proportion of ganglio-series gangliosides relative to GD3 that characterizes the rat retina tissue.

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