| Abstract: | Acetyl-CoA:alpha-glucosaminide N-acetyltransferase is a lysosomal-membrane enzyme deficient in a genetic disorder, Sanfilippo disease type C. The enzyme catalyzes the transfer of an acetyl group from cytoplasmic acetyl-coenzyme A (acetyl-CoA) to terminal alpha-glucosamine residues of heparan sulfate within the organelle. Previous kinetic experiments indicated that the enzyme carries out a transmembrane acetylation via a ping-pong mechanism; the reaction can therefore be dissected into two half reactions--acetylation of the enzyme, and transfer of the acetyl group to glucosamine. Cells derived from patients were found to differ in their ability to perform each half reaction. Five cell lines (derived from three families) were able to catalyze acetylation of the lysosomal membrane and to carry out acetyl-CoA/CoA exchange, whereas a sixth cell line was devoid of this activity. |
