Peroxisomes

catalase and urate oxidase: oxidatitve enzymes

Biogenesis from ER
Fission

PEROXISOMES
lots in liver
Oxidation

Peroxidase
Hydrogen peroxide
Catalase

Detoxification
Ethanol -> Acetaldehyle -> Acetic acid
ADH
ALDH

PEROXISOMES
lots in liver
Oxidation of uric acid to 5-hydroxyisourate

Purine metabolism
Gene for Uricase acid lost in hominoids
nonsense mutation, TGA
Uric acid build up
Uric acid is a strong antioxidant, aging
Tumor lysis syndrome, chemotherapy, hyperuricemia
kidney failure
Gout, acute inflammatory arthritis, uric acid crystals

Peroxisomes

-oxidation of long chain fatty acids

catabolism to 2 carbon molecules
Biosynthesis of plasmalogens
myelin
nerves, cardiovasculature
70% brain myelin
Pentose phosphate pathway
2 enzymes
ATP generation
Ribose metabolism

Myelination

Peroxisomal Import
SS: three amino acids (SerLysLeu) located at the
C-terminus
Soluble receptor proteins in the cytosol
which recognize the targeting signals
docking proteins on the cytosolic surface
(peroxins and PEX genes)
Import resemble protein transport into the
nucleus (folded and oligomeric prots)

PEROXISOMAL DISORDERS
Defects in single enzymes
Myelination defects
Lipid metabolism
Acyl-CoA oxidase deficiency

abnormal neurological development

skeletal malformation
impaired respiration
Cataracts
Downs
Alzheimers
Zellweger syndrome
defect in importing proteins
peroxisomal deficiency

Acyl-CoA

PEROXISOMAL DISORDERS
Defects in PEROXINS (PEX genes) ->
peroxisome biogenesis diseases (PBDs)
Clinical symptoms
Autosomal recessive developmental brain disorders
Skeletal and craniofacial dysmorphism,
Liver dysfunction,
Progressive sensorineural hearing loss
Retinopathy
Zellweger syndrome (children and lethal)
Cerebrohepatorenal syndrome
Cells accumulate very long chain fatty acids (VLCFA)
Impaired neuronal migration, neuronal positioning
brain development.
Reduction in central nervous system (CNS) myelin

ER

Endoplasmic Reticulum

ER resident protein is protein disulfide isomerase (PDI)

SH on cysteines
cysteines in protein domains exposed to either the
extracellular space or the lumen of organelles in the
secretory and endocytic pathways are disulfide-bonded
CA2+ pumps
Storage and Ca2+ binding proteins

cysteine