Acid alpha-glucosidase: Difference between revisions

Latest revision as of 06:08, 11 December 2024

Acid Alpha-Glucosidase

Acid alpha-glucosidase, also known as acid maltase, is an enzyme that plays a crucial role in the breakdown of glycogen into glucose within the lysosomes. This enzyme is encoded by the GAA gene located on chromosome 17 in humans. Deficiency in acid alpha-glucosidase activity leads to the accumulation of glycogen in the lysosomes, resulting in a condition known as Glycogen storage disease type II, or Pompe disease.

Function[edit]

Acid alpha-glucosidase is responsible for catalyzing the hydrolysis of alpha-1,4 and alpha-1,6 glycosidic linkages in glycogen, maltose, and isomaltose. This enzymatic activity is essential for the proper degradation of glycogen into glucose, which is then utilized by the body for energy production. The enzyme functions optimally at an acidic pH, which is characteristic of the lysosomal environment.

Genetic Basis[edit]

The GAA gene provides instructions for synthesizing acid alpha-glucosidase. Mutations in the GAA gene can lead to reduced or absent enzyme activity, causing the accumulation of glycogen in the lysosomes. Over 300 mutations in the GAA gene have been identified, which can result in varying degrees of enzyme deficiency and clinical severity of Pompe disease.

Clinical Significance[edit]

Deficiency of acid alpha-glucosidase results in Pompe disease, a rare autosomal recessive disorder. The disease manifests in various forms, ranging from the severe infantile-onset form to the milder late-onset form. Symptoms of Pompe disease include muscle weakness, respiratory difficulties, and cardiomyopathy. Early diagnosis and treatment are crucial for managing the disease and improving patient outcomes.

Diagnosis and Treatment[edit]

Diagnosis of Pompe disease involves measuring the activity of acid alpha-glucosidase in blood, skin fibroblasts, or muscle tissue. Genetic testing can confirm the diagnosis by identifying mutations in the GAA gene. Treatment options include enzyme replacement therapy (ERT) with recombinant human acid alpha-glucosidase, which can help reduce glycogen accumulation and alleviate symptoms.

Research and Future Directions[edit]

Ongoing research aims to improve the understanding of acid alpha-glucosidase function and the pathophysiology of Pompe disease. Advances in gene therapy and novel therapeutic approaches hold promise for more effective treatments in the future.

Also see[edit]

Template:Glycogen storage diseases Template:Lysosomal storage disorders

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-<br>= Acid Alpha-Glucosidase =
+Acid Alpha-Glucosidase
-'''Acid alpha-glucosidase''' (also known as '''GAA''', '''lysosomal alpha-glucosidase''', or '''acid maltase''') is an enzyme that plays a crucial role in the breakdown of glycogen into glucose within the lysosomes. This enzyme is essential for normal glycogen metabolism, and its deficiency leads to a rare genetic disorder known as Pompe disease.
+Acid alpha-glucosidase, also known as acid maltase, is an enzyme that plays a crucial role in the breakdown of glycogen into glucose within the lysosomes. This enzyme is encoded by the GAA gene located on chromosome 17 in humans. Deficiency in acid alpha-glucosidase activity leads to the accumulation of glycogen in the lysosomes, resulting in a condition known as [[Glycogen storage disease type II]], or Pompe disease.
-== Structure and Function ==
+== Function ==
-Acid alpha-glucosidase is a lysosomal enzyme encoded by the '''GAA''' gene located on chromosome 17q25.2-q25.3. The enzyme is synthesized as a precursor protein that undergoes post-translational modifications, including glycosylation, to become fully active. It functions optimally at an acidic pH, which is characteristic of the lysosomal environment.
+Acid alpha-glucosidase is responsible for catalyzing the hydrolysis of alpha-1,4 and alpha-1,6 glycosidic linkages in glycogen, maltose, and isomaltose. This enzymatic activity is essential for the proper degradation of glycogen into glucose, which is then utilized by the body for energy production. The enzyme functions optimally at an acidic pH, which is characteristic of the lysosomal environment.
-The primary function of acid alpha-glucosidase is to hydrolyze alpha-1,4 and alpha-1,6 glycosidic bonds in glycogen, converting it into free glucose. This process is vital for maintaining cellular energy homeostasis, especially in muscle tissues where glycogen is stored in significant amounts.
+== Genetic Basis ==
+The GAA gene provides instructions for synthesizing acid alpha-glucosidase. Mutations in the GAA gene can lead to reduced or absent enzyme activity, causing the accumulation of glycogen in the lysosomes. Over 300 mutations in the GAA gene have been identified, which can result in varying degrees of enzyme deficiency and clinical severity of Pompe disease.
-== Genetic and Molecular Basis ==
+== Clinical Significance ==
-Mutations in the '''GAA''' gene can lead to a deficiency in acid alpha-glucosidase activity. Over 300 mutations have been identified, including missense, nonsense, and splice-site mutations, as well as small deletions and insertions. These mutations result in varying degrees of enzyme deficiency, which correlate with the severity of Pompe disease.
+Deficiency of acid alpha-glucosidase results in [[Pompe disease]], a rare autosomal recessive disorder. The disease manifests in various forms, ranging from the severe infantile-onset form to the milder late-onset form. Symptoms of Pompe disease include muscle weakness, respiratory difficulties, and cardiomyopathy. Early diagnosis and treatment are crucial for managing the disease and improving patient outcomes.
-== Pompe Disease ==
+== Diagnosis and Treatment ==
-Pompe disease, also known as glycogen storage disease type II, is an autosomal recessive disorder caused by the deficiency of acid alpha-glucosidase. It is characterized by the accumulation of glycogen in the lysosomes, leading to progressive muscle weakness and respiratory difficulties.
+Diagnosis of Pompe disease involves measuring the activity of acid alpha-glucosidase in blood, skin fibroblasts, or muscle tissue. Genetic testing can confirm the diagnosis by identifying mutations in the GAA gene. Treatment options include enzyme replacement therapy (ERT) with recombinant human acid alpha-glucosidase, which can help reduce glycogen accumulation and alleviate symptoms.
-=== Clinical Manifestations ===
+== Research and Future Directions ==
-Pompe disease presents in various forms, ranging from the classic infantile-onset form to the late-onset form:
+Ongoing research aims to improve the understanding of acid alpha-glucosidase function and the pathophysiology of Pompe disease. Advances in gene therapy and novel therapeutic approaches hold promise for more effective treatments in the future.
-* '''Infantile-Onset Pompe Disease''': Symptoms appear within the first few months of life and include hypotonia, cardiomyopathy, and respiratory distress. Without treatment, it is often fatal within the first year.
-* '''Late-Onset Pompe Disease''': Symptoms can appear at any age from childhood to adulthood and primarily involve progressive muscle weakness, particularly affecting the respiratory and skeletal muscles.
-=== Diagnosis ===
-Diagnosis of Pompe disease is confirmed by measuring acid alpha-glucosidase activity in blood, fibroblasts, or muscle tissue. Genetic testing can identify mutations in the '''GAA''' gene, providing a definitive diagnosis.
-== Treatment ==
+== Also see ==
-The primary treatment for Pompe disease is enzyme replacement therapy (ERT) with recombinant human acid alpha-glucosidase. ERT has been shown to improve cardiac and skeletal muscle function, prolong survival, and enhance quality of life, particularly in infantile-onset patients.
+* [[Glycogen storage disease]]
+* [[Lysosomal storage disease]]
-== Research and Future Directions ==
+* [[Enzyme replacement therapy]]
-Ongoing research aims to improve the efficacy of ERT and explore alternative therapies, such as gene therapy and chaperone therapy. Advances in understanding the molecular mechanisms of acid alpha-glucosidase deficiency continue to provide insights into potential therapeutic targets.
+* [[Genetic testing]]
-== Conclusion ==
+{{Glycogen storage diseases}}
-Acid alpha-glucosidase is a critical enzyme in glycogen metabolism, and its deficiency leads to Pompe disease, a serious genetic disorder. Early diagnosis and treatment are essential for managing the disease and improving patient outcomes. Continued research is vital for developing more effective therapies and ultimately finding a cure.
+{{Lysosomal storage disorders}}
-== References ==
+[[Category:Enzymes]]
-* Hirschhorn, R., & Reuser, A. J. J. (2001). Glycogen storage disease type II: Acid alpha-glucosidase (acid maltase) deficiency. In C. R. Scriver, A. L. Beaudet, W. S. Sly, & D. Valle (Eds.), The Metabolic and Molecular Bases of Inherited Disease (8th ed., pp. 3389-3420). McGraw-Hill.
+[[Category:Genetic disorders]]
-* van der Ploeg, A. T., & Reuser, A. J. J. (2008). Pompe's disease. The Lancet, 372(9646), 1342-1353.
+[[Category:Metabolic disorders]]
-* Kishnani, P. S., et al. (2006). Recombinant human acid alpha-glucosidase: Major clinical benefits in infantile-onset Pompe disease. Neurology, 68(2), 99-109.