Thermodynamic determination of plasma and leukocyte beta-hexosaminidase isoenzymes in homozygote and heterozygote carriers for the GM2 gangliosidosis B1 variant

American Journal of Clinical Pathology
J Antonio CasalJ C Tutor

Abstract

In the GM2 gangliosidosis B1 variant, the mutated isoenzyme A of beta-hexosaminidase (Hex) is incapable of hydrolyzing ganglioside GM2 and negatively charged substrates. Biochemical characterization of this lysosomal disease is carried out using synthetic alpha-subunit-specific sulfated substrates, as heat-inactivation assays are not applicable. The apparent enzyme activation energy of Hex using the chromogenic substrate 3,3'-dichlorophenolsulfonphthaleinyl N-acetyl-beta-D-glucosaminide is related directly to the relative proportions of Hex A and Hex B isoenzymes. This thermodynamic variable was used for the study of Hex enzyme heterogeneity in 3 patients with the GM2 gangliosidosis B1 variant and 6 heterozygote carriers. Hex activity was determined at 25 degrees C, 30 degrees C, 35 degrees C, and 37 degrees C in a Cobas Bio analyzer (Roche Diagnostics, Basel, Switzerland), and Arrhenius plot slopes and apparent activation energies were calculated in plasma samples and mononuclear and polymorphonuclear leukocyte lysates. The determination of the Hex isoenzymes in plasma presented a high discrimination power for B1 variant patients but not for heterozygote carriers, in whom false-negative results may be obtained. However, thermo...Continue Reading

References

Jan 1, 1974·Annals of Human Genetics·R J GoldC R Scriver
Oct 1, 1993·DNA and Cell Biology·P Hechtman, F Kaplan
Sep 11, 1999·Clinica Chimica Acta; International Journal of Clinical Chemistry·L F PérezJ C Tutor
Nov 26, 1999·Biochimica Et Biophysica Acta·D J Mahuran
Dec 28, 2002·American Journal of Medical Genetics. Part a·J Antonio CasalJ Carlos Tutor

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