Fatty Acid Beta-Oxidation
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The Process
- Development Process

The Fatty Acid Oxidation Process
-
Fatty Acid Beta-Oxidation
- Fatty Acid Omega-Oxidation
- Fatty Acid Beta-Oxidation Regulation

The Fatty Acid Synthesis Process 
- Fatty Acid Synthesis
- Fatty Acid Synthesis Regulation

Evaluation of used information sources
- GenMAPP database evaluation
- Reactome database evaluation
- Biocarta database evaluation
- KEGG database evaluation
- Genego Metacore evaluation

- Ingenuity database evaluation


Beta
-Oxidation


Beta
-Oxidation results in sequential cleavage of two carbon units from fatty acids. It is an important source of energy for the body during fasting or metabolic stress [1].
Mitochondrial
beta-oxidation is a process involving transport of activated acyl-CoA into the mitochondria and the removal of two carbon acetyl-CoA units. These units are used for the tricarboxylic acid cycle and for the production of ketone bodies.

Carnitine O-palmitoyltransferase (EC: 2.3.1.21) is the overall rate limiting step for
beta-oxidation. Long chain acylcarnitines are passed to carnitine O-palmitoyltransferase (EC: 2.3.1.21) in the inner mitochondrial membrane by catalase (EC: 1.11.1.6). Acyl-CoAs of all chain lengths undergo a series of enzymatic reacties in the mitochondrial matrix, which results in the release of two carbon unit acetyl-CoA and an acyl-CoA molecule that is two carbons shorter. The first reaction is the dehydrogenation of the acyl-CoA to 2-enoyl-CoA, which is catalyzed by Acyl-CoA dehydrogenase (EC: 1.3.99.3). The 2-enoyl-CoA is hydrated to 3-hydroxyacyl-CoA and this reaction is catalyzed by enoyl-CoA hydratase (EC: 4.2.1.17). 3-hydroxyacyl-CoA undergoes 2,3 dehydrogenation to 2-ketoacyl-CoAs, which is catalyzed by 3-Hydroxyacyl-CoA dehydrogenase (EC: 1.1.1.35). To complete one turn of the recursive beta-oxidation cycle acetyl-CoA is released by cleavage of the thioester bond and acyl-CoA is formed, which is catalyzed by Acetyl-CoA C-acyltransferase (EC: 2.3.1.16).



Carnitine shuttle

Sources of carnitine in the diet are meat, fish and dairy. Carnitine is synthesized in the kidneys, liver and brain. Other tissues depend on the uptake of carnitine from the circulation. Carnitine is involved in the transport of in the transport of long-chain fatty acids from the cytosol to the intramitochondrial space where beta-oxidation of fatty acids take place [2].
Entry into the mitochondria starts with the conversion of fatty acyl-coenzyme A to a fatty  acyl-carnitine by carnitine O-palmitoyltransferase (EC: 2.3.1.21) on the inner side of the outer mitochondrial membrane. Fatty acyl-carnitine is transferred into the mitochondrial matrix by carnitine O-acetyltransferase (EC 2.3.1.7) and converted back to fatty acyl-coenzyme A by carnitine O-palmitoyltransferase (EC: 2.3.1.21) on the inner surface of the inner mitochondrial membrane [3].

Peroxisomal Beta-oxidation
[4]

Peroxisomal beta-oxidation has the same mechanism as the beta-oxidation in mitochondria. Through the beta-oxidation pathway a 2-carbon unit is split from each fatty acid in the form of acetyl-CoA. Acetyl-CoA is then degraded in the Krebs cycle. Mitochondria catalyse the Beta-oxidation of the fatty acids derived from the diet. The peroxisomes oxidizing a different set of fatty acids and fatty acids derivatives include very-long-chain fatty acids (VLCFA), pristanic acid (2,6,10,14)-tetramethylpentdecanoic acid and di- and trihydroxycholestanoic acid (DHCA and THCA). VLCFA are derived from dietary sources and are synthesized endogenously from shorter fatty acids. Pristanic acid is derived from dietary sources. Di- and trihydroxycholestanoic acid are intermediates in the formation of the primary bile achids, cholic acid and chenodeoxycholic acid, and these are formed from cholesterol in the liver.
The peroxisomal fatty acid oxidation system is only able to chain-shorten fatty acids and is not able to degrade fatty acids to completion. The shorter chains are transported as carnitine ester from the peroxisomes to the mitochondria, where the degradation will be completed.

The products of beta-oxidation in the peroxisomes have to be shuttled to the mitochondria. Peroxisomes are equipped with different carnitine acyltransferases including carnitine acetultransferase (CAT) and carnitine actanoyltransferase (COT). These allow the formation of carnitine esters inside peroxisomes, followed by export across the peroxisomal membrane. Uptake of carnitine esters into mitochondria occurs via the mitochondrial carnitine/acylcarnitine tranporter (CACT) followed by the retroconversion of the acylcarnitines into the acyl-CoA esters via different acyltransferases, which are present in the mitochondria. An alternative to get the product of beta-oxidation in the peroxisomes in the mitochondria is by cleavage of the acyl-CoA esters into the free acids plus CoASH followed by transport of the free fatty acids to mitochondria.

Peroxisomes contain two acyl-CoA oxidases (EC: 1.3.3.6), one for straight-chain fatty acids and a second one catalyzing the dehydrogenation of 2-methyl branched-chain fatty acids.



 

References:

  1. Vockley J, Whiteman AH. Defects of mitochondrial β-oxidation: a growing group of disorders. Neuromuscular Disorders. 2002 Mar; 12(3): 235-246
  2. Rubio-Gozalbo ME, Bakker, JA, Waterham HR, Wanders RJA. Carnitine-acylcarnitine translocase deficiency, clinical biochemical and genetic aspects. Molecular Aspects of Medicine. 2004 Oct-Dec; 25(5-6): 521-532
  3. McClelland GB. Fat to the fire: the regulation of lipid oxidation with exercise and environmental stress. Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology. 2004 Nov; 139(3): 443-460
  4. Wanders RJA. Peroxisomes, lipid metabolism, and peroxisomal disorders. Molecular Genetics and Metabolism. 2004 Sep-Oct; 83(1-2) 16-27