Coenzyme A

Coenzyme A ( also coenzyme A, short- CoA or CoASH ) is a coenzyme that is used to "activation" of alkanoic acids and their derivatives and is involved in energy metabolism.

It is acyl group donor in acyltransferases ( EC 2.3.NN ) and CoA transferases ( EC 2.8.3.N ).

The insulation was first provided in 1951 by the German biochemist and Nobel laureate later Feodor Lynen in the form of acetyl -coenzyme A ( " activated acetic acid " ) from yeast cells. The elucidation of the structure was carried out two years later by James Baddiley from the British Lister Institute of Preventive Medicine and Fritz Albert Lipmann at Harvard University.

Structure

The coenzyme A molecule made ​​up of several components: these include a nucleotide ( adenosine diphosphate, ADP), a vitamin (pantothenic acid, vitamin B5 ), and an amino acid (cysteine ​​), whereas the synthesis in the body that links together and then slightly be modified.

In detail, the final cysteamine from coenzyme A (also thioethanolamine ) (5), β -alanine, there is (4), pantoic acid (2,4- dihydroxy-3 ,3- dimethylbutyric acid ) (3), diphosphate (2) and the 3 ' phosphorylated adenosine ( 1).

β -alanine (4) and pantoic acid (3) together are referred to as pantothenic acid. Considering this together with the cysteamine ( 5) Speak of the pantetheine (5 4 3). 3' -phospho- adenosine can be conceived together with the diphosphate 3' -phospho- adenosine diphosphate. Accordingly, there is coenzyme A from pantetheine and 3' -phospho- ADP.

Biosynthesis

The synthesis in the animal organism is based on the essential pantothenic acid, to the first use of the pantothenate kinase phosphoryl group, and then use the Phosphopantothenat -cysteine ​​ligase, a cysteine ​​is bound. Once the cysteine ​​was decarboxylated by the Phosphopantothenoylcystein decarboxylase to cysteamine is subject an adenosine monophosphate ( AMP) to the phosphate group, and finally the Adenosine is phosphorylated at the 3'- OH group. The last two steps are catalyzed by various domains of the coenzyme -A synthase.

The detailed procedures for the synthesis including structural formulas see Weblinks section.

Function

The coenzyme A is able to enter into energy- rich compounds via the SH group ( thiol ) of cysteamine share. It is these compounds with the carboxyl groups (-COOH) of alkane and fatty acids with the formation of so-called thioester.

Coenzyme A is thus directly - as acyl -CoA - involved in carbohydrate and protein metabolism - the metabolism of fats and indirectly - as acetyl -CoA.

It is said that coenzyme A binding partner by the formation of high-energy thioester bond activated, because only this way they are able to enter into certain chemical reactions in the body in sufficient speed. Without coenzyme A binding partner would be much slower to react.

Acetyl- CoA

Acetyl coenzyme A ( acetyl- CoA short ) is an "activated " residual acetic acid ( CH 3 CO - ). This is bound to the SH group of the cysteamine moiety of coenzyme A.

Acetyl -CoA is produced in the body in several metabolic processes:

• Firstly, there is the so-called oxidative decarboxylation of pyruvate, which in turn is obtained as a final product of glycolysis, educated, but also by the breakdown of amino acids ( such as L- alanine). The oxidative decarboxylation of pyruvate takes place in the mitochondrion. Here the pyruvate dehydrogenase enzyme complex catalyses the elimination of carbon dioxide CO2 ( the carboxyl group is cleaved, thus " decarboxylation " ) and simultaneously the combination of the residual acetyl residue with the SH group of coenzyme A. It is the original middle carbon atom of the pyruvate is oxidized ( therefore " oxidative ").

• In addition, acetyl -CoA formed in the breakdown of fatty acids in the β - oxidation. Here, the fatty acid cleaved from successively always two carbon atoms in the form of acetyl-CoA. So arise, for example in the degradation of palmitic acid with 16 carbon atoms as part of the β - oxidation of eight molecules of acetyl -CoA. This process also takes place in the mitochondrial matrix.

The formed acetyl -CoA can be broken down in the mitochondrion through the citric acid cycle and respiratory chain completely to CO2 and H2O or can be used again for the synthesis of high-energy compounds such as triglycerides, ketone bodies or cholesterol. These anabolic processes take place partly in the cytosol (eg, fatty acid synthesis), however, the acetyl -CoA can not readily leave the mitochondrion and the transport routes for long-chain carboxylic acids (see below) are blocked him. For the transport of acetyl-CoA from the mitochondria into the cytosol, there is therefore a specific transport system, the so-called citrate shuttle.

Acyl-CoA

Acyl -coenzyme A (short- acyl -CoA) is the name for an "activated " fatty acid. Analogously to the acetyl-CoA is here instead of the acetyl residue of a fatty acid, - an acyl radical - bound to the SH- group.

Acyl -CoA is involved in the degradation of fatty acids ( β - oxidation), by binding the fatty acid. In the synthesis of fatty acids in the body assumes a structurally related prosthetic group of fatty acid - acyl carrier protein called (short ACP) - the role of coenzyme A.

Is formed acyl -CoA by the enzyme acyl -CoA synthetase ( also thiokinase ), this occurs in the cytosol. First, the free fatty acid reacts at the carboxy group (-COOH) with the elimination of ATP diphosphate. The result is the so-called acyl- adenylate. The energy of binding is then used to esterify the Coenzyme A with the fatty acid, this AMP is cleaved. Both steps are catalyzed by the thiokinase.

The breakdown of fatty acids, the acyl-CoA has to be transported into the mitochondria. As well as acetyl-CoA can not independently acyl CoA overcome the inner mitochondrial membrane and is transmitted to the transport of L-carnitine. From this acyl -carnitine said transport form of acyl radical in the mitochondria inside is transferred back to a coenzyme A, so again acyl-CoA is present.

Propionyl- CoA

Propionyl -CoA formed in the metabolism on several occasions. The most popular way is the degradation ( β - oxidation) of odd-numbered fatty acids. After repeated splitting off of a unit of two carbon atoms in the form of acetyl-CoA, a unit of three carbon atoms in the form of propionyl-CoA is left at the end. But also in the degradation of fatty acids with methyl branches formed propionyl -CoA. This also affects the degradation of the branched side chain of cholesterol, as it takes place in the biosynthesis of bile acids - while propionyl-CoA is also cleaved. A very important source of propionyl -CoA represents the degradation of the amino acids isoleucine, valine and methionine, as well as the main pathway of threonine

Propionyl -CoA is converted to succinyl -CoA, which can then enter the citric acid cycle and contributes to its population. To propionyl-CoA is first reacted by the dependent biotin propionyl CoA carboxylase methylmalonyl CoA to D. The methylmalonyl -CoA epimerase then produces the L- isomer. This in turn is converted by the methylmalonyl- CoA mutase, dependent on their function of cobalamin in succinyl -CoA.

But also in the synthesis of fatty acids propionyl-CoA also plays a role. The structure of odd-numbered fatty acids starts with propionyl -CoA. Methyl branches in a fatty acid chain can be produced by chain extension with methylmalonyl -CoA, which is formed by the propionyl -CoA carboxylase of propionyl CoA.