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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:


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

(1)

- OXIDAREA AG

- oxidarea este procesul prin care AG, in forma activa de AcilCoA sunt degradati in mitocondri si/ peroxizomi pana la AcetilCoA, 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
Transportul AG activati in mitocondrie (suntul
carnitinei)
Beta oxidarea p-z in matricea mitocondriala

2.

3.

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.

2. TRANSPORTUL ACIL-CoA DIN CITOSOL


IN MITOCONDRIE

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.

3. - OXIDAREA IN MATRICEA MITOCONDRIALA


II: Hidratarea dublei legaturila -hidroxiacil CoA (p-hidroxiacil CoA).

3. - OXIDAREA IN MATRICEA MITOCONDRIALA

III: Oxidarea -hidroxiacil CoA cu producere de -cetoacil CoA


printr-o reactie NAD-dependenta.

3. - OXIDAREA IN MATRICEA MITOCONDRIALA

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.

BILANTUL ENERGETIC
AL OXIDARII
Energetics
of FA oxidation
ACIDULUI PALMITIC (16C)
e.g. 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

NADH + H+
Total

2 ATP
3 ATP
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

https://www.youtube.com/watch?
v=9fxzKp4DxTU

The palmitic acid (C16:0) is formed by fatty acid synthase complex;


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

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