L-55 Organelle Disorders

Front 1

Peroxisomes

Back 1

Small, single membrane organelle with alkaline pH. Several 100/cell.

Form mostly from preexisting peroxisomes, can also form from ER membrane vesicle which uptakes matrix proteins via transporters.

Front 2

Function of peroxisome

Back 2

Anabolic functions - plasmalogen synthesis, some steps in cholesterol and bile acid biosynthesis

Catabolic functions - beta oxidation of VLCFAs (C24:0, C26:0), phytanic acid alpha oxidation, H2O2 metabolism

Front 3

Peroxisomal targeting signals

Back 3

PTS1: Carboxy terminal Ser-Lys-Leu, binds to peroxin PEX5.

PTS2: Amino terminal 9 aas. Binds to peroxin Pex7.

Front 4

Peroximal biogenesis disorders

Back 4

Defect in peroxisomal targeting

Peroxisomes are abnormal and reduced in number.

Catalase found in cytosol.

Deficient plasmalogen synthesis and beta oxidation of VLCFAs.

Increased excretion of dicarboxylic acids.

Includes Zellweger Cerebrohepatorenal Syndrome and Rhizomelic Chondrodysplasia Punctata.

Front 5

Zellweger Cerebrohepatorenal Syndrome

Back 5

70% caused by Pex1 mutation.

AR, most common peroxisomal biogenesis disorder.

Dysmorphic facial features, eye abnormalities, severe hypotonia, neonatal seizures, renal cortical cysts, hepatomegaly, impaired liver, and psychomotor retardation

Front 6

Rhizomelic Chondrodysplasia Punctata

Back 6

65% due to defect in Pex7 (PTS2 receptor)

Severe shortening of proximal limbs, microcephaly, cataracts.

Decreased plasmalogen and increased phytanic acid.

Front 7

X-linked Adrenoleukodystrophy

Back 7

Single peroxisomal enzyme defect in ABCD1, a VLCFA transporter in peroxisome.

Rapid neurodegenerative course - hyperactive, withdrawn, visual, hearing, and speech impairment with adrenal insufficiency.

Types:

Childhood cerebral (classic) - 35%

Adrenomyeloneuropathy (milder) - 45%

Addison-disease only

Carrier detection and diagnosis by elevated VLCFAs.

Treatment - manage adrenal insufficiency, stem cell transplant, Lorenzo's oil.