La Via Citoplasmatica: Perossisomi
La Via Citoplasmatica: Perossisomi
La Via Citoplasmatica: Perossisomi
perossisomi
The Nobel Prize in Physiology or Medicine 1974
Albert Claude, Christian de Duve, George E. Palade
http://www.nobelprize.org/nobel_prizes/medicine/laureates/1974/duve-facts.html
Christian de Duve
Born: 2 October 1917, Thames Ditton, United
Kingdom
Died: 4 May 2013, Nethen, Belgium
Affiliation at the time of the award: Rockefeller
University, New York, NY, USA, Université
Catholique de Louvain, Louvain, Belgium
Prize motivation: "for their discoveries
concerning the structural and functional
organization of the cell"
http://www.nobelprize.org/nobel_prizes/medicine/laureates/1974/duve-facts.html
… Then serendipity entered the picture.
… Then serendipity entered the picture.
[...] One day, by chance, a scientist purified some cell fractions
and then left them in the fridge. Five days later, after returning to
measure the enzymatic activity of the fractions, they observed the
enzymatic activity levels they were looking for! To ensure there
was no mistake, they repeated the experiment a number of times.
Each time, the results were the same: if they measured the
enzymatic activity using fresh samples, then the activity was only
10% of the activity obtained when they let the samples rest for
five days in the fridge. How could they explain these results?
Enzyme Latency
http://www.nobelprize.org/nobel_prizes/medicine/laureates/1974/duve-lecture.html
[…] If two or more enzymes are present together in the same particles, they will be released together in
this kind of experiment; if in different particles, they may come out separately (Fig. 7).
http://www.nobelprize.org/nobel_prizes/medicine/laureates/1974/duve-lecture.html
[…] If two or more enzymes are present together in the same particles, they will be released together in
this kind of experiment; if in different particles, they may come out separately (Fig. 7).
peroxisomes
I PEROSSISOMI
scoperta.
ATPasi
docking-complex
RING-complex
E3 ubiquitin ligases
L’importo delle proteine della matrice
1. Riconoscimento nel
citosol da parte di
recettori solubili
2. Docking
3. Traslocazione
attraverso la
membrana del
complesso recettore-
cargo
1° gradiente di pH
• Nelle diverse fasi dell’importo si formano oligomeri o dimeri in base allo stato redox
La maggior parte
delle PMP sono
importate nel RE.
DRP: Dynamin-
related proteins
Ruolo alternativo di Pex19 nell’inserimento delle PMP nella
membrana perossisomiale
Caratteristiche tipiche della malattia includono fegato ingrossato, alti livelli di ferro e rame nel sangue.
I sintomi comprendono tratti grossolani della faccia, ipotonia, difficoltà di alimentazione, convulsioni, problemi
cardiaci, epatomegalia, emorragie gastroenteriche.
La prognosi è scarsa. La morte avviene entro il primo anno di vita, causata soprattutto da complicazioni
respiratorie e problemi gastroenterici.
Non esistono cure. Il trattamento è sintomatico e di supporto.
LA SINDROME DI ZELLWEGER
ADRENOLEUCODISTROFIA (ALD)
Nell’ALD, i perossisomi sono privi di Acil CoA sintetasi, l’enzima che lega il CoA agli
acidi grassi a catena lunga.
L’enzima viene però normalmente sintetizzato e la carenza sembra riguardare le
ATPasi Pex1p/Pex6p, o altri specifici trasportatori.