Studies on the metabolism of galactose-6-phosphate in rat heart and brain

Abstract

The subcellular distribution of NADP + and NAD +-dependent glucose-6-phosphate and galactose-6-phosphate dehydrogenases were studied in rat liver, heart, brain, and chick brain. Only liver particulate fractions oxidized glucose-6-phosphate and galactose-6-phosphate with either NADP + or NAD + as cofactor. While all of the tissues examined had NADP +-dependent glucose-6-phosphate dehydrogenase activity, only rat liver and rat brain soluble fractions had NADP +-dependent galactose-6-phosphate dehydrogenase activity. Rat liver microsomal and rat brain soluble galactose-6-phosphate dehydrogenase activities were kinetically different ( K m 's 0.5 m m and 10 m m, respectively, for galactose-6-phosphate), although their reaction products were both 6-phosphogalactonate. Rat brain subcellular fractions did not oxidize 6-phosphogalactonate with either NADP + or NAD + cofactors but phosphatase activities hydrolyzing 6-phosphogalactonate, galactose-6-phosphate and galactose-1-phosphate were found in crude brain homogenates. In addition, galactose-6-phosphate and 6-phosphogalactonate were tested as inhibitors of various enzymes, with largely negative results, except that 6-phosphogalactonate was a competitive inhibitor ( K i = 0.5 mM) of rat brain 6-phosphogluconate dehydrogenase.