07 peroxi er
DESCRIPTION
peroxisomeTRANSCRIPT
Peroxisomes
catalase and urate oxidase: oxidatitve enzymes Biogenesis from ER Fission
PEROXISOMES lots in liver
Oxidation Peroxidase
Detoxification Ethanol -> Acetaldehyle -> Acetic acid ADH ALDH
Hydrogen peroxide
Catalase
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 β-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 (Ser–Lys–Leu) 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