Last edited: 9/7/2021

4. PEROXISOMES
Cell Biology | Peroxisomes: Zellweger Syndrome, Refsum's Medical Editor: Abigail S. Xu, RPh
Disease, Adrenoleukodystophy

OUTLINE (2) α-oxidation

BCFA get into peroxisome via ABCD1
I) FUNCTIONS OF PEROXISOMES conversion of branched chain fatty acid (BCFA) to very
II) PEROXISOMAL DISORDERS
long chain fatty acid (VLCFA)
III) REVIEW QUESTIONS
cut of branches
IV) REFERENCES
VLCFA can then undergo β-oxidation

I) FUNCTIONS OF PEROXISOMES (B) METABOLISM OF ETHANOL

Ethanol can be metabolized by
o smooth E.R.
o peroxisomes
Ethanol Metabolism in Peroxisomes
ethanol enter peroxisome
ethanol is broken down to acetaldehyde
utilize hydrogen peroxide (H2O2) [from β-oxidation]
o generate water (H2O) and oxygen (O2)

(C) BILE ACID ACTIVATION AND METABOLISM

Bile acid intermediates (not yet active) are taken into
peroxisomes
Enzymes in peroxisomes activate the bile acids
Activated bile acids can be released from peroxisomes
and go to smooth E.R.

(D) CHOLESTEROL SYNTHESIS

Acetyl-CoA from β-oxidation can combine with other
acetyl-CoA to synthesize cholesterol
Cholesterols are not entirely synthesized in peroxisomes
o Cholesterol intermediates are made in
peroxisomes
o Sent to smooth E.R. to produce cholesterol
Importance of cholesterol
Figure 1. Summary of Function of Peroxisomes o Cell membrane
 maintain fluidity
(A) FATTY ACID METABOLISM
 especially in temperature changes
Types of Fatty Acids: o Steroid hormones
 Testosterone
(i) Very Long Chain Fatty Acids (VLCFA)  Estrogen
(ii) Branched Chain Fatty Acids (BCFA) o Bile Acid synthesis
ABCD1 transporters (E) PLASMALOGEN SYNTHESIS
o transport fatty acids into peroxisomes
Acyl-CoA
(1) β-oxidation o Fatty acids remaining after VLCFA undergo β-
VLCFA get into peroxisome via ABCD1 oxidation
VLCFA undergo 4 Steps “O HOT” Glycerol can be taken up by peroxisomes and get
converted to dihydroxyacetone phosphate (DHAP)
(i) Oxidation [Recall: Glycolysis]
(ii) Hydration (Addition of water) DHAP combines with fatty acids to make
(iii) Oxidation phospholipids, particularly plasmalogen
Plasmalogen
(iv) Thiolation
o Incorporated into myelin
End products o myelin sheaths wrap around axons of neurons in the
o Acetyl-CoA central and peripheral nervous system
 2 Carbon Molecule
o Acyl-CoA
 Remaining after very long chain fatty acid is
broken down
 Can undergo β-oxidation again
o Hydrogen Peroxide (H2O2)
 ↑VLCFA oxidized to Acetyl-CoA and Acyl-CoA
 ↑H2O2 generated from water and oxygen

Peroxisomes CELL BIOLOGY: Note #1. 1 of 4

 (F) REDUCE FREE RADICAL DAMAGE (b) Seizures
Hydrogen peroxide is produced a lot during β-oxidation
o Free radical
(ii) Jaundice
Electron Transport Chain (ETC) generates lots of free • Liver not able to process bilirubin (pigment)
radicals • ↑bilirubin in blood
Oxygen (O2) • Bilirubin deposit in skin and sclera of eyes

(iii) Polycystic Kidney Disease

• Affect development of renal tubules
Free radicals
o dangerous and damaging (B) REFSUM’S DISEASE
o bind to and damage
 DNA
 Proteins
 Lipids
o Macromolecules are important to organelles and
membranes
o Damage to them causes cellular dysfunction
Catalase
o Enzyme in peroxisome
o Convert harmful hydrogen peroxide into water and
oxygen
o Prevent build-up of hydrogen peroxide that can lead Figure 3. Pathophysiology and Manifestations of Refsum’s
to free radical damage Disease
(1) Pathophysiology
II) PEROXISOMAL DISORDERS
Autosomal recessive disorder
(A) ZELLWEGER SYNDROME ↓Genes involved in α-oxidation
o α-oxidation is involved in the conversion of branched
chain fatty acids into very long chain fatty acids
↑branched chain fatty acids (BCFA)
(2) Manifestations
BCFA build up in tissues

(i) Central Nervous System

(a) Retinitis Pigmentosa
• Accumulation of BCFA in retina
• Night blindness
• Visual changes
Figure 2. Pathophysiology and Manifestations of Zellweger • Can also cause cataract
Syndrome
(b) Ataxia
(1) Pathophysiology
• Damage to cerebellum
Autosomal recessive disorder
o Needs two mutant alleles (c) Neuropathy
↓PEX gene • Damage to peripheral nerves
o PEX gene codes for peroxins
o Peroxin: protein essential in making peroxisome (ii) Ichthyosis
↓Peroxisomes • Accumulation in skin
o ↑Very Long Chain Fatty Acids (VLCFA)
 Since ↓β-oxidation (iii) Epiphyseal Dysplasia
o ↑Branched Chain Fatty Acids (BCFA) • Accumulate in epiphyseal plates, affecting
o Ethanol accumulation growth
 Due to ↓ethanol metabolism • Shortening of 4th toe
o ↑H2O2
 Cannot convert it to water and oxygen
o ↓Cholesterol, Plasmalogen synthesis
(2) Manifestations
Accumulation of VLCFA, BCFA, ethanol, hydrogen
peroxide in different tissues, causing damage
Neuro-hepato-renal syndrome

(i) Central Nervous System

(a) Hypotonia
• Neurodegeneration in muscles
• Common in babies: Floppy baby syndrome

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 (C) ADRENOLEUKODYSTROPHY III) REVIEW QUESTIONS
1) Ethanol is broken down into what in the
peroxisomes?
a) Water
b) Oxygen
c) Acetaldehyde
d) Acetyl-CoA

2) What is combined with fatty acids to make

phospholipids?
Figure 4. Pathophysiology and Manifestations of
Adenoleukodystrophy a) Glycerol
b) DHAP
(1) Pathophysiology c) Acetyl-CoA
d) Acyl-CoA
X-linked recessive disorder
o More common in males
↓ABCD1 gene 3) An autosomal recessive disorder that affects the
↓ABCD1 protein PEX gene, leading to accumulation of VLCFA, BCFA,
o ABCD1 protein brings in VLCFA and BCFA into ethanol, and hydrogen peroxide
peroxisomes to be metabolized a) Zellweger Syndrome
b) Refsum’s disease
↓metabolism of fatty acids since they cannot get into c) Adrenoleukodystrophy
peroxisomes d) None of the above
Accumulation of VLCFA and BCFA in tissues
(2) Manifestations 4) A peroxisomal disorder that affects genes involved
in α-oxidation
(i) Dementia a) Zellweger Syndrome
• Accumulation in central nervous system b) Refsum’s disease
• Progressive neurodegeneration c) Adrenoleukodystrophy
d) None of the above
(ii) Adrenal Crisis
• Accumulation in adrenal cortex
5) X-linked recessive disorder that affects ABCD1 gene
• Very fatal in children expression
a) Zellweger Syndrome
(a) ↓↓Aldosterone Production b) Refsum’s disease
• Produced by the Zona Glomerulosa c) Adrenoleukodystrophy
d) None of the above
(b) ↓↓Cortisol Production
CHECK YOUR ANSWERS
• Produced by Zona Fasciculata
IV) REFERENCES

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