Reactome | GAA hydrolyzes lysosomal glycogen

GAA hydrolyzes lysosomal glycogen

Stable Identifier

R-HSA-9036727

Type

Reaction [transition]

Species

Homo sapiens

Compartment

lysosomal lumen

Synonyms

GAA hydrolyzes alpha(1,6) linkages in lysosomal glycogen, GAA hydrolyzes alpha(1,4) linkages in lysosomal glycogen

ReviewStatus

5/5

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While most glycogen is cytosolic, glycogen granules are also found in lysosomes, which they are thought to enter by autophagy. Once in lysosomes, the polysaccharide component of the granules is degraded by a single enzyme, lysosomal alpha-glucosidase (GAA), which hydrolyzes both alpha(1,4) and alpha(1,6) linkages to yield free glucose (Brown et al. 1970). The fate of the glycogenin protein component of the granules has not been studied; it is thought to be degraded by the diverse lysosomal proteases (Muller et al. 2012).
Mutations that reduce the activity of GAA are associated with glycogen storage disease type II (Pompe disease) (Hirschhorn & Reuser 2001; Leslie & Tinkle). The most active forms of GAA are 70 and 76 kDa polypeptides generated by removal of both aminoterminal and carboxyterminal fragments (Brown et al. 1970; Hoefsloot et al. 1988; Wisselaar et al. 1993).

Literature References

PubMed ID	Title	Journal	Year
21767668	Specific functions of lysosomal proteases in endocytic and autophagic pathways Müller, S, Dennemärker, J, Reinheckel, T	Biochim. Biophys. Acta	2012
8420990	Structural and functional changes of lysosomal acid alpha-glucosidase during intracellular transport and maturation Wisselaar, HA, Kroos, MA, Hermans, MM, van Beeumen, J, Reuser, AJ	J. Biol. Chem.	1993
5264799	Simultaneous absence of alpha-1,4-glucosidase and alpha-1,6-glucosidase activities (pH 4) in tissues of children with type II glycogen storage disease Brown, BI, Brown, DH, Jeffrey, PL	Biochemistry	1970
3049072	Primary structure and processing of lysosomal alpha-glucosidase; homology with the intestinal sucrase-isomaltase complex Hoefsloot, LH, Hoogeveen-Westerveld, M, Kroos, MA, van Beeumen, J, Reuser, AJ, Oostra, BA	EMBO J.	1988