Peroxisome

Question 1

Describe the general peroxisome

Answer 1

Contains around 50 enzymes (pH 7.5) made on free ribosomes. Present in all tissue and carry out Oxidative (gen H2O2) reactions. Contains catalase (peroxidase) to destroy excess H2O2.
Involved in biosynth degradative and detox reactions

Question 2

What is the formation pathway of Peroxisomes

Answer 2

Orginate from ER and pre-existing peroxisomes.

Peroxin (R) import cytosolic proteins and lipids

Question 3

Describe the import signal

Answer 3

Proteins made in cytosol, C term SKL (ser-lys-leu) import signal (another on N term) binds to perox translocaters (Peroxin: PEX genes) requiring ATP and already folded proteins

Question 4

What are the functions of the perox

Answer 4

Biosynth and Degenerative

Question 5

What are the biosynth processes in perox

Answer 5

Plasmalogen synth (ether PL), bile acid synth (derived from chol in liver) Lipid BS (chol and dolichol in sER)

Question 6

What are the degenerative processes in perox

Answer 6

VLCFA beta-oxidation, Purine catabolism (Xanthine Oxidase), H2O2

Question 7

Describe the perox reactions

Answer 7

1. Oxidase uses O2 to remove H-atoms from organic substrates (RH2 + O2 -> R + H2O2). For uric acid, AA, FAs, purines.
2. Catalase uses h2o2 to oxidase toxins (alch) in liver and kidney. (h2o2 +Rh2 -> R + 2 h2o) when h202 accumulates (2h2o2 -> 2h2o + o2 therefore elim h2o2)

Question 8

Describe Fatty Acid oxidation

Answer 8

Beta-oxidation of very long chain FAs (VLCFA) greater than 24C, initiated in perox until C10 than completed in mt.
FA oxidation is major source of matabolic energy (fa - acetyl coa - cytosol (biosynth of chol and bile))

Question 9

Describe Purine catabolism

Answer 9

Nucleic acid purines (AG) degraded to uric acid using Xanthine oxidase
AMP - IMP - Hypoxanthine - Xanthine * - Uric acid * - Urate
Guanine directly to Xhanthine
*= X oxidase rxn (hypoxan +o2+h20 -> Xan + h202) (xanth + h2o -> uric acid + h2o2)

Question 10

Describe peroxisome synth fx

Answer 10

1. Plasmologen synth - PL with HC chain linked to glycerol by ether bond in membrane compartments of heart and brain (85% myelin)
2. Bile acid synth
3. Lipid Synth

Question 11

Describe Hyperuricanemia

Answer 11

Gout (arthritis) Tx: allopurinol = xanthine oxidase inhib

Question 12

What effects are from a plasmalogen defect

Answer 12

Abnormal nerve cell myelination

Question 13

Describe Zellwager Spectrum

Answer 13

PEX mutation = defect in peroxisome biogen - failure of importing perox proteins - empty perox.
Diag= Zellweiger syn, neonatal adreno leukodystrophy, infantile refsum disease, hyperpipecolactemia

Question 14

What is X-linked adrenoleukodystrophy (XALD)

Answer 14

Defect in membrane protein importing VLCFAs

Question 15

Describe Zellweiger syndrome

Answer 15

AR, Cong, perox dont recognize SKL signal - empty perox
VLCFA increased in blood, acc in glial cell membrane leading to abnormal brain development due to neuronal migration defect and hypomylination
Accumulate in liver lead to heptamegaly and liver fail = no bile = decreased fat absorb and ATP production leading to muscle weakness
Neurologic dysfunction = Hypotaneriema, hyperflexic, seize, large fontenelles, death at 6-12 months

Question 16

What is XALD

Answer 16

Defect in transport of VLCFA into perox therefore accumulation in cells, myelin breaks and adrenal atrophy.
Onset is 5-10 yrs with signs of apathy, behavior changes, spasticity, ataxia, visual loss, death