Peroxisome

Introduction – Peroxisome

Peroxisomes are small, membrane-bound organelles found in eukaryotic cells. They are involved in a variety of cellular processes, including the breakdown of fatty acids, the detoxification of harmful substances, and the synthesis of certain types of lipids.

Overview – Peroxisome

• Structure
  • membrane-bound vesicle
  • contain several important enzymes
    • catalase
    • hydrogen-transferring enzymes
    • lipid oxidizing enzymes
      • Refsum disease
        • autosomal recessive 
        • due to mutations in PHYH or PEX7 gene resulting in defects in alpha-oxidation leading to a build up of phytanic acid
        • presentation
          • vision loss
          • anosmia

Function – Peroxisome

• Function
  • degradation of very long chain fatty acids (VLCFAs)
    • > 24 carbons
    • via β-oxidation
    • reduces by 14 carbons and then sends to mitochondria
    • deficient in Zellweger syndrome
      • build-up of VLCFAs in peroxisomes
      • impaired myelin synthesis
        • severe neurological symptoms
      • hepatomegaly
      • death < 1 year
        • can increase lifespan with diet low in VLCFAs
      • AR
      • other examples of peroxisomal disorders
        • neonatal adrenoleukodystrophy (NALD)
  • bile acid synthesis
    • derived from cholesterol
  • phospholipid modification
    • alter phosphatidylserine and phosphatidylethanolamine
  • degradation of hydrogen peroxide
    • via catalase
    • degrades hydrogen peroxide produced in β-oxidation of fatty acids

Studies

• Biogenesis and dynamics: Research has focused on understanding the mechanisms of peroxisome biogenesis and the processes that regulate peroxisome size and number within cells. This includes studies on peroxisome fission and fusion, which are important processes for maintaining peroxisome homeostasis.
• Peroxisomal metabolism: Many studies have investigated the enzymes and metabolic pathways involved in peroxisomal metabolism. This includes studies on the beta-oxidation of fatty acids, the detoxification of harmful substances, and the synthesis of specialized lipids.
• Peroxisomal disorders: Researchers have identified several peroxisomal disorders, including Zellweger syndrome, rhizomelic chondrodysplasia punctata, and X-linked adrenoleukodystrophy. These disorders result from defects in peroxisome biogenesis or metabolism and are associated with a range of neurological and developmental problems.
• Peroxisomes and disease: Peroxisomes have been implicated in a range of diseases, including cancer, Alzheimer’s disease, and diabetes. Research has focused on understanding the role of peroxisomes in disease development and progression and identifying potential therapeutic targets.

Treatment

• Dietary changes: In some cases, a change in diet can help manage peroxisomal disorders. For example, patients with certain types of peroxisomal disorders may benefit from a diet low in very-long-chain fatty acids.
• Medications: Some medications can be used to treat the symptoms of peroxisomal disorders. For example, medications to reduce the amount of bile acids in the body can be used to treat Zellweger syndrome, a severe peroxisomal disorder.
• Gene therapy: In some cases, gene therapy may be an option for treating peroxisomal disorders. This involves replacing the faulty gene with a healthy one using viral vectors.

Complications

• Neurological problems: Many peroxisomal disorders affect the nervous system, leading to developmental delay, seizures, and other neurological problems.
• Vision and hearing problems: Certain peroxisomal disorders can cause vision and hearing problems, including blindness and deafness.
• Liver dysfunction: The liver is a major site of peroxisomal metabolism, and many peroxisomal disorders can cause liver dysfunction, including cirrhosis and liver failure.
• Skeletal abnormalities: Some peroxisomal disorders can result in skeletal abnormalities, including shortened bones, scoliosis, and other skeletal deformities.
• Metabolic abnormalities: Peroxisomal disorders can also lead to a range of metabolic abnormalities, including hypoglycemia, hyperammonemia, and other imbalances in the body’s metabolic processes.
• Impaired immune function: Some peroxisomal disorders can impair immune function, making patients more susceptible to infections.
• Respiratory problems: In some cases, peroxisomal disorders can lead to respiratory problems, including difficulty breathing and respiratory failure.

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