The human perspective
Diseases that Result from Abnormal Peroxisomal
Function
Gerald Karp <<CELL AND MOLECULAR BIOLOGY>> 4th Edition
Some facts about peroxisomes
Peroxisomes (microbodies) are simple, membranebound vesicle with a diameter of 0.1 to 1.0 um.
Peroxisomes are multifunctional organelles, containing
more than 50 enzymes involved in such diverse
activities as the oxidation of very-long-chain fatty acids
(VLCFAs) and the synthesis of plasmalogens.
These organelles were named “peroxisomes”
because they are the site of synthesis and
degradation of hydrogen peroxide (H2O2), a highly
reactive and toxic oxidizing agent.
Plasmalogen: an unusual class of phopholipids in which one of the fatty
acids is linked to glycerol by an ether linkage rather than an ester linkage
Abundant in the Myelin sheaths that insulate axons in the brain
peroxisomal diseases
Empty peroxisomes
Genes mutation
Enzymes
fail to be
imported
proteins
involved in
the uptaking
Machinery for
transport
ZS
Zellweger syndrome
赵苇格氏症
A single peroxisomal
enzyme absence
VLCFAs accumulate
in the brain
Defect in a
membrane protein
that transports VLCFAs
ALD
adrenoleukodystrophy
肾上腺脑白质营养不良
ALD : adrenoleukodystrophy
ZS: Zellweger syndrome
VLCFAs: Very-long-chain fatty acids
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• Adrenoleukodystrophy (ALD) is a rare, inherited metabolic disorder
that afflicts the young boy Lorenzo Odone, whose story is told in the
1993 film "Lorenzo's oil." In this disease, the fatty covering (myelin
sheath) on nerve fibers in the brain is lost, and the adrenal gland
degenerates, leading to progressive neurological disability and
death.
• People with ALD accumulate high levels of saturated, very long
chain fatty acids in their brain and adrenal cortex because the fatty
acids are not broken down by an enzyme in the normal manner. So,
when the ALD gene was discovered in 1993, it was a surprise that
the corresponding protein was in fact a member of a family of
transporter proteins, not an enzyme. It is still a mystery as to how
the transporter affects the function the fatty acid enzyme and, for
that matter, how high levels of very long chain fatty acids cause the
loss of myelin on nerve fibers.
• More recently, all the transporters related to ALD protein have been
found in the yeast Saccharomyces cerevisiae, and a mouse model
for the human disease has been developed. These and other
molecular biology approaches should further our understanding of
ALD and hasten our progress toward effective therapies
What is Zellweger Syndrome?
Zellweger syndrome is a rare, congenital (present at birth) disorder characterized by the
reduction or absence of peroxisomes (cell structures that rid the body of toxic substances) in
the cells of the liver, kidneys, and brain. Zellweger syndrome is one of a group of genetic
disorders called peroxisomal diseases that affect brain development and the growth of the
myelin sheath, the fatty covering-which acts as an insulator-on nerve fibers in the brain. The
most common features of Zellweger syndrome include an enlarged liver, high levels of iron
and copper in the blood, and vision disturbances. Some affected infants may show prenatal
growth failure. Symptoms at birth may include lack of muscle tone and an inability to move.
Other symptoms may include unusual facial characteristics, mental retardation, seizures, and
an inability to suck and/or swallow. Jaundice and gastrointestinal bleeding may also occur.
Is there any treatment?
There is no cure for Zellweger syndrome, nor is there a standard course of treatment.
Infections should be guarded against to prevent such complications as pneumonia and
respiratory distress. Other treatment is symptomatic and supportive.
What is the prognosis?
The prognosis for individuals with Zellweger syndrome is poor. Death usually occurs within 6
months after onset, and may be caused by respiratory distress, gastrointestinal bleeding, or
liver failure.
What research is being done?
The NINDS supports research on genetic disorders including leukodystrophies such as
Zellweger syndrome. The goals of this research are to increase scientific understanding of
these disorders, and to find ways to prevent, treat, and cure them.