Lysosomes and Peroxisomes

Lysosomes

Structure:

• Single-membrane organelle, enclosed by a lipid bilayer.

• Contains numerous hydrolytic enzymes capable of breaking down substances such as proteins, nucleic acids, lipids, and carbohydrates.

• Size: 0.2 – 0.6 micrometers.

• The internal environment has a low pH (4.5 – 5.5).

Lysosomal Membrane Proteins:

• Glycosylated, enhancing membrane stability.

Important Lysosomal Proteins:

• SYT7 protein: Pumps H+ from lysosomes into the cytoplasm and transports it to the cell membrane for membrane regeneration.

• NPC1 protein: Pumps cholesterol into the cytoplasm to stabilize intracellular cholesterol.

• V-type H+-ATPase protein channel: Converts ATP energy → ADP + Pi, pushing H+ into the lysosome to maintain a pH of 4.4 – 5.5.

Functions of Lysosomes:

• Degradation of substances taken in from outside the cell.

• Renewal of damaged organelles.

• Maintaining homeostasis and cellular stability.

Formation of Lysosomes:

• Lysosomes are organelles of the cell, lacking their own genome.

• The formation of lysosomes depends on the needs of the cell.

• Pre-enzymes are synthesized at the ribosome –> Golgi –> endoplasmic reticulum –> primary lysosome.

Phagocytosis and Autophagy:

• Secondary lysosome is formed from the combination of primary lysosomes and phagocytic vesicles or autophagic vesicles.

• Phagocytic vesicles: Formed by “capturing” foreign bodies from outside the cell.

• Autophagic vesicles: Formed by the endoplasmic reticulum wrapping around old, damaged organelles.

Tay-Sachs Disease:

• Due to the lack of the gene encoding the synthesis of hexosaminidase A enzyme, a crucial enzyme in the hydrolysis of glycolipids.

• Glycolipid accumulates and stagnates, causing nerve cell degeneration, leading to developmental delay and mental disorders.

• Autosomal recessive genetic disease on chromosome 15.

General Features of Lysosomal Diseases:

• Disorders in the processes occurring within the lysosome.

• Enzyme deficiency.

• Often characterized by substance precipitation.

• Severe impact on the body.

Approximately 30 different diseases are related to lysosomes.

Silicosis (Pneumoconiosis):

• Common occupational disease in miners and other industries.

• Dust particles are small and not retained by the cilia and mucus of the bronchi.

• They reach the alveoli and are absorbed by macrophages.

• The main chemical component of dust is silicate, an inorganic substance that is insoluble and cannot be broken down by lysosomal enzymes.

• Silicate accumulates in lysosomes, leading to lysosomal membrane rupture, releasing enzymes and stimulating inflammation.

• Prolonged inflammation leads to fibrosis of lung tissue.

Pompe Disease:

• Lysosomes lack the acid alpha-glucosidase (CAA) enzyme.

• Glycogen accumulates in lysosomes due to its inability to be broken down.

• Symptoms: Heart weakness, poor muscle tone, enlarged liver, heart defects.

Gaucher Disease:

• Caused by a deficiency in the Golgi enzyme phosphottransferase, responsible for attaching the pre-enzyme to the mannose 6-phosphate complex.

• Lysosomes do not receive and lack glucocerebrosidase, leading to an inability to break down glucosylceramide.

• Glucosylceramide accumulates in macrophages, manifesting the disease.

• Symptoms: Enlarged liver and spleen, abnormal long bones, skull deformities, joint misalignments.

• Type 1: Predominant, survivable.

• Type 2: Early death.

• Type 3: Characterized by interaction of type 1 and 2, affecting the nervous system, manifesting between 3 – 10 years old.

Treatment for Lysosomal Diseases:

• Substrate reduction therapy.

• Surgical removal.

• Enzyme enhancement:

• Gene therapy.

• Enzyme replacement therapy (recombinant, stem cells).

• Enzyme induction therapy (medication).

Peroxisomes

Structure:

• Single-membrane organelle, spherical, 0.2 – 1 micrometer in size.

• Contains oxidative enzymes such as acid oxidase, catalase, ureate oxidase, involved in metabolism and energy production.

• Capable of self-division.

• Lack their own genome.

• Often concentrated in the liver and kidneys.

Number of Peroxisomes:

• Each cell has approximately 500 peroxisomes.

Functions of Peroxisomes:

• Oxidation of toxic compounds to cells such as uric acid, amino acids, ethanol, methanol, fatty acids…

• Synthesis of lipids, amino acids, lysine, cholesterol, and dolichol.

• Production of bile acid in liver tissue.

• Contains enzymes for the synthesis of plasmalogen, essential in the structure of the heart and brain membranes.

• Performs oxidation reactions producing H2O2 (toxic), using the catalase enzyme to reduce H2O2 to H2O or using H2O2 to oxidize other organic compounds.

Peroxisomal Enzymes:

• Synthesized by free ribosomes.

In yeast and plants:

• Oxidation of fatty acids is only performed inside peroxisomes.

Cholesterol and dolichol:

• Synthesized both inside peroxisomes and in the endoplasmic reticulum.

Process of Peroxisome Formation:

• Involved in Peroxine proteins (Pex3 and Pex19), fixed on the buds of the endoplasmic reticulum –> forming the peroxisome membrane.

• Other proteins are formed by translation in the cytoplasm –> enter and form a complete peroxisome.

When Peroxisomes Mature:

• Enzymes inside and various metabolic activities.

Peroxisome Diseases:

• Disorders from peroxisome defects:

• X-linked adrenoleukodystrophy (ALD): Accumulation of fatty acid chains –> fatty acids enter the peroxisome –> excess leading to destruction of the myelin sheath in nerve cells.

• Disorders in the synthesis of substances within peroxisomes:

• Zellweger: Due to mutations occurring in at least 10 different genes of import proteins –> occurs in the first 10 years of life.

• Process: Mutations in 10 genes –> proteins cannot enter the peroxisome –> gradual degradation of peroxisomes –> inability to oxidize toxic substances.

Characteristics of Zellweger Syndrome:

• Protruding forehead, flat face, wide nose.

• Wide-set eyes, cataracts, glaucoma.

• Hand deviation towards the radius.

• Prominent patella.

• Genital malformations.

• Reduced muscle tone.