1. The document summarizes the process of 硫-oxidation of fatty acids, where fatty acids are broken down in the mitochondria to produce acetyl-CoA through repeated cycles.
2. There are three main stages: activation of fatty acids to acyl-CoA in the cytosol, transport of acyl-CoA into the mitochondria via carnitine shuttle, and four reactions of 硫-oxidation in the mitochondrial matrix that cleave off two-carbon acetyl-CoA units.
3. Each cycle of 硫-oxidation involves oxidation, hydration, another oxidation, and cleavage reactions to liberate acetyl-CoA from the fatty acid chain, with the shortened acyl-
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1. 硫 -Oxidation of Fatty Acids
Mrs. Poonam Sunil Aher (M Pharmacy, PhD)
Assistant Professor, HOD Pharmaceutical Chemistry
Department
Sanjivani College of Pharmaceutical Education and
Research (Autonomous),
Kopargaon, Ahmednagar-423603 (M.S.), INDIA
Mobile: +91-9689942854
2. 硫 -Oxidation of Fatty Acids
The fatty acids in the body are mostly oxidized by 硫-oxidation.
硫 -Oxidation may be defined as the oxidation of fatty acids on the 硫 -
carbon atom.
This results in the sequential removal of a two carbon fragment,
acetyl CoA.
Fatty acid oxidation -stages and tissues The 硫 -oxidation of fatty acids
involves three stages
l. Activation of fatty acids occurring in the cytosol
ll. Transport of fatty acids into mitochondria
lll. B-Oxidation proper in the mitochondrial matrix.
Fatty acids are oxidized by most of the tissues in the body.
However, brain, erythrocytes and adrenal medulla cannot utilize fatty
acids for energy requirement.
3. 1. Fatty Acids Activation
Fatty acids are activated to acyl CoA by thiokinases or acyl CoA synthetases.
The reaction occurs in two steps and requires ATP, coenzyme A and Mg2+.
Fatty acid reacts with ATP to form acyladenylate which then combines with
coenzyme A to produce acyl CoA
In the activation, two high energy phosphates are utilized, since ATP is
converted to pyrophosphate (PPi).
The enzyme inorganic pyrophosphatase hydrolyses PPi to phosphate (Pi).
The immediate elimination of PPi makes this reaction totally irreversible
5. 2. Transport of Acyl CoA into mitochondria
The inner mitochondrial membrane is impermeable to fatty acids.
A specialized carnitine carrier system (carnitine shuttle) operates to
transport activated fatty acids from cytosol to the mitochondria.
This occurs in four steps
1. Acyl group of acyl CoA is transferred to carnitine, catalysed by carnitine
acyltransferase I (present on the outer surface of inner mitochondrial
membrane).
2. The acyl-carnitine is transported across the membrane to mitochondrial
matrix by a specific carrier protein.
3. Carnitine acyl transferase ll (found on the inner surface of inner
mitochondrial membrane) converts acyl-carnitine to acyl CoA.
4. The carnitine released returns to cytosol for reuse
7. 3. Proper 硫 -Oxidation
Each cycle of 硫 -oxidation, liberating a two carbon unit-acetyl CoA, occurs in a
sequence of four reactions
1. Oxidation : Acyl CoA undergoes dehydrogenation by an FAD-dependent
flavoenzyme, acyl CoA dehydrogenase. A double bond is formed between 留 and 硫
carbons (i.e.,2 and 3 carbons).
2. Hydration : Enoyl CoA hydratase brings about the hydration of the double bond
to form 硫 -hydroxyacyl CoA.
3. Oxidation : 硫 -Hydroxyacyl CoA dehydrogenase catalyses the second oxidation
and generates NADH. The product formed is 硫 -ketoacyl CoA.
4. Cleavage : The final reaction in 硫 -oxidation is the liberation of a 2 carbon
fragment, acetyl CoA from acyl CoA. This occurs by a thiolytic cleavage catalysed
by 硫 -ketoacyl CoA thiolase .
The new acyl CoA, containing two carbons less than the original, renters the 硫 -
oxidation cycle.
The process continues till the fatty acid is completely oxidized.