U01.01.025 Peroxisome

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Learning Objectives

  • Identify the four metabolic “powerhouse” functions of the Peroxisome.
  • Distinguish between $\beta$-oxidation of VLCFA and $\alpha$-oxidation of branched-chain fatty acids.
  • Contrast the clinical presentations of Zellweger syndrome, Refsum disease, and Adrenoleukodystrophy.
  • Understand the importance of plasmalogens in the central nervous system.

 

1. Peroxisomal Functions

Peroxisomes are membrane-enclosed organelles that handle specific metabolic “trash” and synthetic tasks that the mitochondria cannot.

  • \beta-oxidation of VLCFA: Breakdown of Very-Long-Chain Fatty Acids (strictly peroxisomal).
  • \alpha-oxidation: Breakdown of branched-chain fatty acids (like phytanic acid).
  • Catabolism: Breakdown of amino acids and ethanol.
  • Synthesis: Production of bile acids and plasmalogens.
    • Note: Plasmalogens are essential phospholipids for the white matter of the brain.

2. Zellweger Syndrome

A global failure of peroxisome biogenesis.

  • Genetics: Autosomal recessive; mutated PEX genes.
  • Pathophysiology: Failure to form peroxisomes leading to the accumulation of pipecolic acid.
  • Presentation: Hypotonia (“floppy baby”), seizures, jaundice, hepatomegaly, and distinct craniofacial dysmorphia. Usually fatal in infancy.

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3. Refsum Disease

A specific defect in \alpha-oxidation.

  • Genetics: Autosomal recessive.
  • Pathophysiology: Inability to degrade phytanic acid, leading to its buildup.
  • Presentation: A constellation of neurological and sensory issues: retinitis pigmentosa (vision loss), anosmia, hearing loss, ataxia, and ichthyosis (scaly skin).
  • Management: Dietary restriction (avoiding chlorophyll-containing foods/ruminant fats) and plasmapheresis.

4. Adrenoleukodystrophy (ALD)

A defect in peroxisomal \beta-oxidation of VLCFAs.

  • Genetics: X-linked recessive; mutation in the ABCD1 gene.
  • Pathophysiology: VLCFAs cannot be transported into peroxisomes, causing buildup in the adrenal glands, white matter (leuko-) of the brain, and testes.
  • Presentation: Progressive loss of neurologic function and adrenal crisis.

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Summary Table: Peroxisomal Disorders

Disease Defect Key Finding
Zellweger Biogenesis (PEX genes) Hypotonia, early death.
Refsum \alpha-oxidation Retinitis pigmentosa, scaly skin.
ALD \beta-oxidation (ABCD1) X-linked, adrenal crisis.

 

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