Peroxisomes

-contain ~50 enzymes (pH 7.5)

-made on free ribosomes in cytosol and folded ones imported directly into peroxisome
(resembles transport into nucleus?)
-present in all tissues (liver & kidney)
-carry out oxidative reactions
-generate H2O2 for oxidative purposes
-contain catalase (peroxidase) to destroy xs H2O2
-involved in biosynthetic, degradative and detoxification reactions
-originate from ER & pre-existing peroxisomes
-peroxins (receptors in peroxisome membrane) import cytosolic proteins
-growth by uptake of specific peroxisomal proteins and lipids from cytosol
-can undergo fission
-peroxisome import signal on the proteins made in the cytosol. It is SKL (Ser-Lys-Leu) usually
at the C terminal (another on N terminal). Import signals bind to peroxisomal translocators;
Peroxins (PEX genes). Import requires ATP and only folded proteins enter peroxisome.
-biosynthetic functions include:
-plasmalogen synthesis. Plasmalogen is in the membrane of cells that form the
myelin sheath, and thus this ether phospholipid is important in myelination and
neuronal function. Membrane components of heart and brain (80-90% of myelin
membrane phospholipid). Thus, a deficiency would lead to abnormalities in nerve cell
myelination
-bile acid synthesis (derived from cholesterol; occurs in liver)
-lipid biosynthesis: cholesterol and dolichol (also made by sER)
-degradative functions include:
-VLCFA B-oxidation (unique to peroxisomes, once smaller can be degraded in
mitochondria).
-VLCFAs contain greater than 24 carbons, once down to 10, completed in
mitochondria.
-fatty acid oxidation = major source of metabolic energy
-fatty acids > AcetylCoA > cytosol (used for biosynthesis of cholesterol & bile
acids)
-Purine catabolism (xanthine oxidase)
-nucleic acid purines (A, G) = degraded to uric acid: Xanthine oxidase
-xanthine oxidase catalyzes hypoxanthine to xanthine, and xanthine to uric acid
-this purine degradation process, along with xanthine oxidase, important in gout
-gout have uric acid crystal accumulations (hyperuricemia) in joints > arthritis
-usually first sign of gout is swelling of big toe
-first treatment for gout is anti-inflammatory drugs, then dieting, and finally
sometimes allopurinol: xanthine oxidase inhibitor
-H2O2
-Peroxisomal reactions
-oxidases use O2 to remove H from organic substrates
-catalase
-uses H2O2 to oxidize toxins (ie: alcohol): Peroxidation reaction which is
important in liver and kidney
-& when xs H2O2 accumulates, turns it into 2H2O and O2 (elimination of 2H2O2)
-Peroxisomal disorders
-Zellweger spectrum: PEX mutations = defective peroxisomal biogenesis
failure to import peroxisomal proteins > empty peroxisomes (similar to I-cell,
but not a defect in SKL tag because ~50 enzymes, instead defective peroxins


and thus dont recognize SKL sequence. Peroxins dont function as import
proteins anymore!)
-Zellweger syndrome, Neonatal adrenoleukodystrophy (NALD), Infantile
Refsum disease, Hyperpipecolactaemia
-Zellweger syndrome
-autosomal recessive, congenital
-peroxins dont recognize Ser-Lys-Leu (SKL) > failure to import peroxisomal
enzymes
-peroxisome deficiency
-VLCFA accumulates in blood & tissues
-lack of plasmalogen
-accumulation of VLCFAs in glial cell membrane (no B-oxidation) > abnormal
brain development
-neuronal migration defects
-hypomyelination
-accumulation of VLCFAs in liver > hepatomegaly & liver failure
-lack of bile acids > decreased fat absorption > decrease ATP > muscle
weakness
-severe neurological dysfunction
-hypotonia, hyporeflexia, seizures, mental retardation, dysphagia
-dysmorphic features
-prominent forehead, hypertelorism, large fontanelles
-hepatomegaly & liver dysfunction
-death 6-12 months
-X-linked Adrenoleukodystrophy (XALD) = defective membrane protein that
imports VLCFAs
-most common peroxisomal disorder
-defect in transport of VLCFA into peroxisome > defective breakdown of
VLCFAs
-VLCFAs accumulate in
-brain (glial cells) > myelin breakdown
-adrenal cortex > adrenal atrophy
-onset 5-10yo: apathy, behavioral changes
-spasticity, ataxia, visual loss
-death few years later