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Beta Oxidation
Beta Oxidation
INTRODUCTION
Oils and fats are major energy reserves of living beings – also known as triacyl glycerols
They are hydrolysed in cytoplasm by lipases to give glycerol and fatty acids
The glycerol formed enter glycolytic pathway by being converted to dihydroxyacetone
phosphate
The free fatty acids are then released from the tissue, become tightly bound to serum
albumin and in this form are carried via the blood to other tissues for oxidation
Β - OXIDATION PATHWAY FOR SATURATED FATTY ACIDS WITH
EVEN NUMBER OF CARBON ATOMS
β – oxidation is defined as the oxidation of fatty acids on the β carbon atom (Franz Knoop
proposed this pathway)
In β oxidation fatty acids are degraded by the sequential of two carbon fragment, acetyl CoA
Several enzymes known collectively as fatty acid oxidase enzyme system are found in the
mitochondrial matrix, adjacent to the respiratory chain.
These enzymes catalyse β – oxidation of long chain fatty acids to acetyl CoA, mitochondria is
the site of β – oxidation
Fatty acids are oxidized by most of the tissues of the body, however brain, erythrocytes and
adrenal medulla cannot utilize fatty acids for energy
β – oxidation pathway involves three stages
1. Activation of fatty acids in cytosol
2. Transport of activated fatty acids into mitochondria
3. β – oxidation in the mitochondrial matrix
CoASH
1. MECHANISM OF FATTY ACID ACTIVATION CATALYZED BY ACYL-COA
SYNTHETASE
Activated long-chain fatty acyl-CoA cannot directly cross the inner mitochondrial
membrane
They penetrate the inner mitochondrial membrane only in combination with carnitine
The enzyme carnitine acyl transferase catalyses transfer of the fatty acyl group from its
thioester linkage with CoA to an oxygen-ester linkage with the hydroxyl group of
carnitine.
Since the standard free energy change of this reaction is small, the acyl carnitine linkage
evidently represents a high energy bond.
The acyl carnitine ester so formed then passes through inner membrane into the matrix
through specific transport system
3. β – oxidation
Fatty acids are dismembered through the β – oxidation of fatty acyl-CoA, a process that occurs
in four reactions
1. Formation of a trans α, β -double bond through dehydrogenation by the flavoenzyme acyl-
CoA dehydrogenase
Hydration of the double bond by enoyl-CoA hydratase (EH) to form a 3-L-hydroxyacyl-CoA.
3. NAD+- dependent dehydrogenation of this β - hydroxyacyl-CoA by 3-L-hydroxyacyl-CoA
dehydrogenase (HAD) to form the corresponding β -ketoacyl-CoA.
4. C α -C β cleavage in a thiolysis reaction with CoA as catalyzed by β -ketoacyl-CoA thiolase (KT;
also called just thiolase) to form acetyl-CoA and a new acyl-CoA containing two less C atoms
than the original one
Energetics of β – oxidation
The overall reaction for each cycle of β – oxidation is represented as
Cn Acyl CoA+ FAD +NAD+ +CoASH
For complete oxidation, it will undergo 7 cycles producing 8 acetyl CoA, 7FADH2 and 7NAD
During fasting, the nutritional glucose supply becomes progressively limiting, and glucose
production is maintained through glycogen breakdown (glycogenolysis) and de novo
glucose synthesis (gluconeogenesis).
Glycogen stores are limited, and ultimately gluconeogenic precursors, which include
lactate, pyruvate, glycerol, and specific amino acids, are the sole sources of glucose.
Because proteolysis is mainly responsible for the net generation of gluconeogenic
precursors, oxidation of fatty acids is essential as an alternative to prevent rapid erosion of
protein mass.
This adaptive response is mediated by the neuroendocrine system, which among other
mechanisms increases adipose lipolysis. Such lipolysis drives increased FAO and hepatic
ketogenesis and thereby leads to decreased glucose uptake and oxidation.
This competition between the oxidation of fatty acids and glucose is also known as the
glucose–fatty acid, or Randle, cycle
Ketone bodies
Acetyl-CoA produced by oxidation of fatty acids in liver mitochondria can be further
oxidized via the citric acid cycle
These compounds, which together with acetone are referred to as ketone bodies,
serve as important metabolic fuels for many peripheral tissues, particularly heart
and skeletal muscle.
The brain, under normal circumstances, uses only glucose as its energy source (fatty
acids are unable to pass the blood–brain barrier), but during starvation, ketone
bodies become the brain’s major fuel source.