Lysosomal glucosidase is an enzyme that breaks down glycogen in lysosomes. It is essential for breaking glycogen down into glucose to provide energy to cells. Deficiencies in lysosomal glucosidase can lead to glycogen storage disorders like Pompe disease, where glycogen builds up and causes muscle and organ damage. Diagnosis involves testing for enzyme activity and genetic mutations. Treatment may include enzyme replacement therapy to break down glycogen accumulations.

1. Group L Presentation
LYSOSOMAL GLUCOSIDASE
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2. INTRODUCTION
 What is lysosomal glucosidase: lysosomal glucosidase is another name for acid
alpha-glucosidase, an enzyme that breaks down glycogen in the lysosomes of
cells.
 Lysosomes are structures that serve as recycling centers within cells. They use
digestive enzymes to break down complex molecules into simpler ones that can
be used by cell.
 Lysosomal glucosidase is essential for the degradation of glycogen to glucose in
lysosome
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3. THE LYSOSOME
LYSOSOMES are membrane bound organelles found in the cytoplasm
of the eukaryotic cell and are responsible for maintaining the cellular
cleanliness and recycling.
They are also called the suicidal sacs or bags
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4. Functions of Lysosome
 They play a role in the removal of dead of old cells
 Play a role in apoptosis or programmed cell death
 They are responsible for breaking down molecules of nutrient or foreign
particles that enter the cell.
 In cellular metabolism, lysosomes are responsible for autophagy a process in
which the cell recycles unneeded parts of itself to create new parts and to
provide energy
 Also undergoes metabolic regulation where metabolic pathways are regulated
in mammals to give out energy. For example glycogen to glucose
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5. LYSOSOMAL ENZYMES
Such as the lysosomal glucosidase responsible for breakdown of
glycogen
The hydrolitic enzymes like the acid hydrolases that break down
macro-molecules like the nucleic acids, proteins, and the polysac
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6. GLYCOSIDASES
These are enzymes that are responsible for the hydraulic breakdown of
carbohydrates into monomers.
This process occurs in the intestines and it also helps in the absorption
of sugars into the blood stream Glucosidase.
Has several types which among them are alpha and beta glucosidase In
lysosomes alpha glucosidase is a digestive enzyme that is used to
breakdown complex sugars to simpler sugars called glucose which is
the main source of energy.
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7. Cont….
Alpha glucosidase acts on the alpha -1,4-glocosidic bonds between
glucose molecules in complex carbohydrates.
Inhibiters of alpha glucosidase are used as medicines to manage blood
sugar levels in individuals with diabetes.
They act by slowing down the digestion of carbohydrates which leads
to more gradual increase in blood glucose levels.
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8. ROLE OF LYSOSOMAL GLUCOSIDASE
 The breakdown of complex glycogen to simpler glucose
 Primarily takes place in cytoplasm but also in lysosomes(must be acidic) of hepatocytes and myocytes
to promote cellular homeostasis of glucose.
 Stimulated by glucagon(from pancreas) and adrenaline(from adrenal glands) respectively
 Process and enzymes involved include:
 1 Glycogen phosphorylase- promotes formation of G-1 phosphate
 2 Transferase- attaches 3 glucose molecules to the main chain
 3 Acid alpha glucosidase – a debranching enzyme that cleaves off glucose molecules at every branch
by hydrolysing the alpha 1,6 glycosidic bonds to form a single chain of molecules which can be further
cleaved off by glycogen phosphorylase.
 4 Phosphogluco mutase – converts glucose 1 phosphate to glucose 6 phosphate
 5 G-6 phosphatase – coverts G-phosphate to glucose only in hepatocytes
 6 glucose is transported to the cytoplasm for cellular functions.
 Note: Glucose produced from lysosomal glycogenolysis in liver cells can only be transported into the
bloodstream if there is extreme demand for glucose. In muscles, the G-6 phosphate produced in
lysosomal or cytoplasmic glycogenolysis is only used in muscle cells and not transported into the
bloodstream.
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10. PATHWAYS INVOLVING LYSOSOMAL
GLUCOSIDASE
Lysosomal glucosidase is an enzyme responsible for the
breakdown of glycogen, a storage form of glucose, within
lysosomes. The metabolic pathway involved in lysosomal
glucosidase is known as the glycogenolysis pathway.
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11. IMPORTANCE OF THE PATHWAY
 essential for normal cellular function and particularly important in organs such as the liver, heart
 And skeletal muscles.
 Helps maintain cellular homeostasis by eliminating waste products and recycling essential nutrients
 regulates glycogen storage levels, prevents excessive accumulation and maintains balance in the body
 It ensures the proper breakdown of glycogen and the release of glucose, which serves as a vital energy source
for cells.
 essential for normal cellular function and particularly important in organs such as the liver, heart And skeletal
muscles.
 Helps maintain cellular homeostasis by eliminating waste products and recycling essential nutrients
 regulates glycogen storage levels, prevents excessive accumulation and maintains balance in the body
 It ensures the proper breakdown of glycogen and the release of glucose, which serves as a vital energy source
for cells.
 Deficiencies in this enzyme can lead to a group of genetic disorders known as Glycogen Storage
Disorders(GSDs). These disorders can cause the build up of glycogen in various tissues and organs, leading to a
range of symptoms and complications.e.g Pompe disease, cori disease, Mcardlea
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12. DISORDERS ASSOCIATED WITH
LYSOSOMAL GLUCOSIDASE
DEFICIENCY
 These disorders included pompe disease and Gaucher’s disease.
 Pompe disease is a genetic disorder caused by mutations in the GAA gene which
encodes for aloba-glucosidase, If this gene is mutated in any way, alpha-glucosidase
may be produced in insufficient amount ma or not at all. As a result, glycogen
builds up in the cells particularly the muscles leading to muscle weakness, difficulty
breathing and heart problems.
 Gaucher’s disease is a genetic disorder causes by mutations in the GBA gene which
encodes for glucocerebrosidase. This enzyme breaks down glucocerebroside into
glucose and ceramide. Mutations in the GBA gene lead to accumulation of
glucocerebroside in body cells resulting in symptoms such as enlarged spleen,
enlarged liver, bruising, lung problems among others
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14. DIAGNOSIS AND TREATMENT
 Enzyme Activity Assay: This is a fundamental test to measure GAA activity in
blood.
 Genetic Testing: DNA analysis can identify mutations in the GAA gene, confirming
the diagnosis and providing information about the specific genetic variant.
 Muscle Biopsy: This can reveal glycogen accumulation in muscle cells,
METHODE
 Genetic Testing: Identifying specific mutations in the GAA gene can confirm the
diagnosis and provide important information for genetic counseling.
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15. TREATMENT
 Enzyme Replacement Therapy (ERT): This helps break down
accumulated glycogen.
 Chaperone Therapy: This involves the use of small molecules that
can stabilize the misfolded GAA enzyme,
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16. RECENT RESEARCH AND DIRECTION
 Gene Therapy Advances: Researchers are exploring gene therapy as a potential treatment option for
lysosomal glucosidase deficiency, aiming to introduce functional copies of the deficient gene into
affected cells.
 Enzyme Replacement Therapy (ERT) Improvements: Efforts are being made to enhance the
efficacy and accessibility of enzyme replacement therapy (ERT) for lysosomal glucosidase deficiency.
This involves optimizing the delivery methods and increasing the availability of the therapeutic
enzyme.
 Emerging Small Molecule Therapies: Novel small molecule therapies are being investigated to
target specific pathways associated with lysosomal glucosidase deficiency, potentially offering
alternative treatment options or complementing existing therapies.
 Precision Medicine Approaches: Researchers are exploring personalized treatment strategies that
consider individual patient variations, aiming to optimize the effectiveness of interventions and
improve overall patient outcomes.
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17. CONCLUSION
 Lysosomal glucosidase is an enzyme primarily found in the lysosome
 It plays a crucial role in the break down of complex carbohydrates particularly Glycogen into glucose
 Lysosomal Glucosidase is involved in the glycogen degradation pathway where it breaks down
glycogen into glucose units
 Dysfunction or deficiency leads to accumulation of glycogen in the lysosome causing storage
diseases such as Pompe disease
 Pompe disease is a rare, inherited and often fatal disorder affecting muscle and nerve cells
 Early diagnosis and treatment is crucial for managing the symptoms and improving the patients life
 In this case Enzyme Replacement Therapy (ERT) is the commonly used
 recombinant human acid alpha-Glucosidase(rhGAA) is administered by intravenous infusion
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18. REFERENCES
 Brown, T. A., Smith, A. B., & Johnson, C. D. (Year). Biochemistry: Principles and
Practice. Publisher.
 Ernesto R. Bongarzone, in Basic Neurochemistry (Eighth Edition),
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19. THANKS FOR YOUR
ATTENTION
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