Beta oxidation

As β - oxidation is called the biochemical mechanism of degradation of fatty acids. The term refers to the held on β - carbon atom of the fatty acid oxidation. The β - oxidation was formerly known as fatty acid spiral.

The β - oxidation was discovered in 1904 by Franz Knoop in Freiburg. It was not until 50 years later, however, the exact mechanism of this pathway has been elucidated. The β - oxidation takes place in animal cells, mostly in the mitochondria, in plant cells in the glyoxysomes.

• 2.1 degradation of even-numbered saturated fatty acids 2.1.1 FAD - dependent oxidation
• 2.1.2 hydration
• 2.1.3 NAD - dependent oxidation
• 2.1.4 thiolysis

Preparation

Before the actual β - oxidation can commence, the otherwise very unreactive fatty acids must first be in the cytosol, " activated", and then transported from the cytosol into the mitochondrial matrix, the place in which the β - oxidation takes place.

Activation of fatty acid

The aim of activation is the formation of acyl-CoA by transferring fatty acid to coenzyme A. This produces an energy-rich thioester bond that allows for the further reaction steps. In the first step, ATP is cleaved to AMP and pyrophosphate to that (also: acyl- adenylate ) directly to the formation of acyl -AMP is utilized. Parallel to the cleavage of the pyrophosphate in simple phosphate by pyrophosphatase, the fatty acid can be esterified with elimination of AMP by the energy released with coenzyme A. The thus activated form of fatty acid is called acyl- CoA. Both reactions are catalyzed by a fatty acid -CoA ligase.

Transport into the mitochondrial matrix

After the acyl group is transferred with elimination of coenzyme A by the enzyme carnitine acyltransferase I on carnitine and active transport into the matrix of the mitochondria. This process is catalyzed by the carnitine - acylcarnitine transporter ( CACT ) of the antiport acyl -carnitine mitochondrial into the matrix and transported carnitine out simultaneously. In the matrix, the acyl group is replaced by carnitine acyltransferase II of carnitine and transferred back to CoA. While the activated fatty acid is now the decomposition available carnitine is exported back into the cytosol by the CACT. The acyl-CoA - activation is not reversible, an activated fatty acid is broken down.

Actual β - oxidation

Depending on the nature of the fatty acid (number of carbon atoms, position and configuration of any double bonds), the sequence of the degradation of the even-numbered, saturated fatty acids may vary as optionally additional reactions are required to suitable substrates for the enzymes of β - oxidation to create or because other reaction products are obtained as acetyl -CoA.

Degradation of even-numbered saturated fatty acids

The actual loss can be divided into four consecutive steps of:

FAD - dependent oxidation

Hydration

NAD - dependent oxidation

Thiolysis

Degradation of odd-numbered fatty acids

The degradation of these fatty acids is different from that of the even by the fact that in the end not acetyl -CoA, but propionyl -CoA remains. This is now in several steps to succinyl -CoA, a metabolite of the citric acid cycle, rebuilt.

To the propionyl-CoA is first carboxylated with ATP cleavage of the α - carbon atom. This reaction is catalyzed by propionyl -CoA carboxylase, which contains as a cofactor Biotin ( vitamin B7). The result (S)- methylmalonyl- CoA, which is converted by the methylmalonyl -CoA racemase in the (R ) - methylmalonyl- CoA in the next step. Finally, the carboxyl group is represented by the methylmalonyl- CoA mutase, vitamin B12 - dependent, transmitted from the α - carbon atom to the carbon atom of the methyl group, which is formed succinyl-CoA, can be added to the citric acid cycle.

Degradation of unsaturated fatty acids

Since most of the double bonds of the naturally occurring unsaturated fatty acids have a cis- configuration, but to accept the enzymes of β - oxidation only substrates in the trans configuration, they must first be converted by specific isomerases. Another problem directly consecutive double bonds (-CH = CH -CH = CH-) dar. These must be reduced so that only one double bond ( -CH 2- CH = remains CH -CH2-) to enzymes of the to be detected.

Energy yield

The formed during the β - oxidation of acetyl -CoA can be either further degraded in the citric acid cycle, or for the synthesis of ketone bodies are used. In the case of the degradation caused per round of β - oxidation, a FADH2 and NADH H , which deliver 1.5 or 2.5 ATP via the respiratory chain. Each acetyl- CoA, which is metabolized by the tricarboxylic acid cycle, also enables the synthesis of 10 ATP. For example, 106 molecules of ATP can the complete degradation of a molecule of palmitic acid are formed: palmitic acid contains 16 carbon atoms and is therefore reduced to a total of eight acetyl -CoA, with seven molecules of FADH2 and NADH H are formed, since the cycle is traversed seven times. However, since ATP was digested with hydrolysis of two high-energy compounds to AMP for activation of the fatty acid in the cytosol, resulting net: 7 x 14 10 - 2 = 106 ATP. In comparison, occur during complete degradation of one molecule of glucose only 32 molecules of ATP.

β - oxidation in other organelles

Fatty acids are degraded not only in the mitochondria. In plants and yeasts, for example, the breakdown of fatty acids takes place exclusively in the glyoxysomes or peroxisomes. In humans, very long chain fatty acids ( at least 22 C atoms ) are first mined in the peroxisomes into shorter products. Longer-chain rare fatty acids ( 26-28 carbon atoms with a plurality of double bonds ) can be metabolised by peroxisomes of brain cells. These fatty acids can then be metabolised shortened as described above by the mitochondrial β - oxidation.

For the transport of long-chain fatty acids into the peroxisome of the human ALD protein is used instead of carnitine. If this carries a defect, this leads to the expression of a disease, the X- adrenoleukodystrophy.

The degradation of fatty acids in peroxisomes has certain peculiarities: For example, the first enzyme oxidized by coenzyme A- activated fatty acid directly by means of oxygen. The result is a trans - Δ2 - enoyl -CoA and hydrogen peroxide ( H2O2). This reaction is catalysed by an acyl -CoA oxidase (EC 1.3.3.6 ) and bypasses the transfer of the electrons to FAD (see above). H2O2 is disproportionated by catalase to oxygen and water. ( Enoyl -CoA hydratase, L-3- hydroxyacyl -CoA dehydrogenase ) In addition, the activities of the following enzymes are combined in a multifunctional enzyme. Finally, the peroxisomal thiolase not cleave fatty acids, the chain length is less than eight carbon atoms.

Reverse beta- oxidation

The reversal of the beta- oxidation does not occur in nature, although there is no fundamental impediment. This reversal would be even more efficient than the normal fatty acid synthesis and could be realized in the appropriate microorganisms that produce biofuels and raw materials efficiently. The reversal of the beta- oxidation pathway in E. coli has 2011 Rice University in Houston and is an example of successful Bioengineering dar. These had to be deregulated and composed first partial routes for shorter and longer chains; 2 competing glucose fermentation are turned off; 3 initiating enzymes ( thiolase ) are terminating enzymes for the desired products ( acyl -CoA reductase, Aldehyd-/Alkoholdehydrogenase, thioesterase ) inserted / overexpressed and 4 are added for the desired reactants.