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Welcome, everybody. My
name is Michael Schrader.
I'm a professor of
cell biology in
the Department of Biosciences
at the University of Exeter.
In my short talk, I would like
to address peroxisomal
disorders.
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Peroxisomes were first
identified in 1954
by Johannes Rhodin through
electron microscopy.
They were characterised
biochemically by
Nobel laureate Christian
de Duve in the 1960s.
He revealed their
oxidative nature and role
in hydrogen peroxide
metabolism and named them
peroxisomes because
peroxisomes contain
several oxygen-consuming
oxidases,
which generate
hydrogen peroxide,
which can then be
degraded by catalase,
one of the most prominent
peroxisomal marker enzymes.
In 1973, Sidney Goldfischer
and colleagues discovered
that Zellweger syndrome
patients lack peroxisomes,
and this was the first
link to human disease.
Later on, the important role of
peroxisomes in the
breakdown of fatty acids,
for example, very long-chain
fatty acids, was discovered,
and very long-chain
fatty acids are also now
a specific biomarker for
peroxisomal disorders.
The first gene defect was
only identified in 1992.
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What are the major metabolic
pathways of peroxisomes?
Peroxisomes possess
three ABCD transporters.
These are ABC transporters,
which are involved in the
uptake of a variety of
fatty acid substrates
into the peroxisomes.
The peroxisomes possess
a β-oxidation pathway
for the degradation of,
for example, very long
chain fatty acids,
also for the oxidation of
bile acid intermediates.
This usually generates
hydrogen peroxide,
which is generated
by a key enzyme
in the pathway by an
acyl-CoA oxidase.
It also generates acyl-CoA
and chain-shortened fatty acids,
which are routed to mitochondria
for further β-oxidation.
Peroxisomes also harbour an
alpha oxidation pathway for
the degradation of
branched-chain fatty acids
such as phytanic acid,
and phytanic acid can be
alpha oxidised into
pristanic acid,
which can then be degraded
by peroxisomal β-oxidation.
However, peroxisomes
also synthesise lipids,
for example, ether
phospholipids.
The key enzymes for
ether phospholipid
synthesis are peroxisomal.
First, the enzymes
which generate
the specific ether bond
do this in peroxisomes,
but the peroxisomes
cooperate with
the endoplasmic reticulum to
complete ether
lipid biosynthesis.
We distinguish two major groups
of peroxisomal disorders.
