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Oxidarea acizilor grai

Sinteza acizilor grai


OXIDAREA ACIZILOR GRASI

AG= importanta sursa de energie


Oxidarea- procesul in care energia este produsa prin
degradarea AG

Exista cateva tipuri de oxidare a AG:

(1) - oxidarea AG
(2) - oxidarea AG
(3) - oxidarea AG
(1) - OXIDAREA AG

- oxidarea este procesul prin care AG, in forma activa de Acil-


CoA sunt degradati in mitocondri si/ peroxizomi pana la Acetil-
CoA, molecula ce intra in cK.

Are loc in multe tesuturi incluzand ficatul, rinichii si cordul.


- OXIDAREA AG nu are loc in creier.
ETAPELE - OXIDARII

- OXIDAREA AG implica 3 etape:

1. Activarea AG in citosol
2. Transportul AG activati in mitocondrie (suntul
carnitinei)
3. Beta oxidarea p-z in matricea mitocondriala
ACTIVAREA ACIZILOR GRASI

Are loc in prezenta AG tiokinazei (acil COA sintetaza) prezenta in citosol.


Tiokinaza necesita 2ATP, COASH, Mg++.
Produsii rezultati sunt acil COA si apa.
2. TRANSPORTUL ACIL-CoA DIN CITOSOL
IN MITOCONDRIE
Intrucat MMI este impermeabila pt CoA, acilCoA traverseaza MMI
printr-un mecanism de transport special: suntul carnitinei

1. Grupurile acil CoA sunt transferate carnitinei cu formare de


acyl carnitine, in prezenta carnitin- aciltransferazei din MME

2. Acilcarnitina ulterior traverseaza MMI cu ajutorul translocazei

3. Grupul acil se reantoarce in matrice in prezenta acil transferazei II.

4. In final, carnitina se intoarce in citosol cu ajutorul translocazei, in


schimbul acil carnitinei.
3. - OXIDAREA IN MATRICEA
MITOCONDRIALA

Exista 4 etape ale -oxidarii


I Oxidarea in prezenta dehidrogenazei FAD dependente

II Hidratarea in prezenta Hidratazei

III Oxidarea in prezenta dehidrogenazei NAD dependente

Step IV Tioliza in prezenta Tiolazei


3. - OXIDAREA IN MATRICEA MITOCONDRIALA
I:
Prima reactie este oxidarea acil CoA - acil CoA dehidrogenazei la -
acil CoA nesaturat (enoil CoA).

FAD este acceptor de hidrogen.


II: Hidratarea dublei legaturila -hidroxiacil CoA (p-hidroxiacil CoA).
III: Oxidarea -hidroxiacil CoA cu producere de -cetoacil CoA
printr-o reactie NAD-dependenta.
IV: Scindarea a unui fragment cu doi atomi de carbon prin ruperea
legaturii dintre carbonii si
Enzima: tiolaza
Eliberarea de acetil CoA determina un
rest acil cu 2 atomi de C mai putin.

Aceasta molecula de acil CoA este


substratul urmatoarei runde de oxidare
incapand cu acil CoA dehidrogenaza.

Ciclul se repeta pana cand toti atomii de


C ai acilCoA original sunt convertiti la
acetilCoA.

In ultima runda, un acil CoA (butiril CoA)


este clivat la 2 acetil CoA.
Energetics of FA oxidation
BILANTUL ENERGETIC AL OXIDARII
e.g. Palmitic
ACIDULUI (16C):
PALMITIC (16C)

1. -oxidarea acidului palmitic se va repeta de 7 ori producnd 8


molecule de acetil CoA.
2. In fiecare ciclu, pentru 1 acetilCoA: FADH2 si NADH+H+ ce vor fi
transportate in lantul respirator mitocondrial
FADH2 2 ATP
NADH + H+ 3 ATP
Total 5 ATP/ cycle
Astfel, 7 cicluri (16:2-1) 5x7 = 35 ATP
3. Fiecare acetil CoA oxidat in ciclul citric produce 12 ATP (8 x 12 = 96
ATP)
4. 2 ATP sunt utilizati in activarea AG .
5. Energia castigata = Energia produsa - Energia utilizata
= 35 ATP + 96 ATP - 2 ATP = 129 ATP

https://www.youtube.com/watch?v=pmfeF1DUTOM
3.4. Synthesis of fatty acids
Occurs primarily in the liver, but also in adipose tissue and
mammary glands
Takes place in the cytosol
The major fatty acid produced in our body is palmitic acid (C16:0).
The process starts in the mitochondria and is finalized in cytoplasm.
Enzyme: fatty acid synthase
2 subunits (2 identical monomers)
Each monomer has 7 enzyme activities
Acetyl CoA is formed in the
mitochondria from pyruvate (the
end product from glycolysis).
Acetyl CoA cant cross
mitochondrial membrane.
Oxaloacetate (OAA) + Acetyl
CoA citrate
Citrate is transported by citrate
shuttle to cytosol, where is
cleaved to OAA + Acetyl CoA
Pyruvate carboxylase and
pyruvate dehydrogenase
(PDH) are enzymes present in
mitochondria only; are
catalyzing irreversible reactions.
In cytoplasm
Citrate lyase cleaves citrate to Acetyl CoA and OAA
NADPH is required for fatty acid synthesis
Acetyl CoA is tranformed in Malonyl CoA by :
Acetyl CoA carboxylase, process that
requires biotin and ATP
Is stimulated by insulin
Acetyl CoA carboxylase is rate-limiting, highly regulated by AMP levels
The palmitic acid (C16:0) is formed by fatty acid synthase complex;
https://www.youtube.com/watch?v=9fxzKp4DxTU

The elongation is a repetitive cycle that uses acetylCoA-ACP and


malonylCoA-ACP.
New fatty acid is not reoxidized in liver:
Inhibition of carnitine acyl transferase CPT1, by
malonyl CoA

Longer fatty acids are made in Smooth ER by similar


reactions involving malonyl CoA

Other enzymes desaturate the FA-CoA to form


the unsaturated derivatives; NADH is required.
Insulin:
Activates acetylCoA carboxylase,
stimulating the synthesis of fatty
acids;
The inactive form of acetylCoA
carboxylase is the phosphorylated
form. The activation of the enzyme
is realized by a protein
phosphatase, which is stimulated by
insulin.
Favours lipogenesis and inhibits
lipolysis, decreasing the release of
fatty acids and glycerol (from
triglycerides), thus inhibiting the
release of fatty acids from adipose
tissue.
Glucagon
Inactivates acetylCoA carboxylase,
inhibitig the fatty acids synthesis