Coenzyme A

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Structural formula
Structural formula of coenzyme A
General
Surname Coenzyme A
other names
  • [(2 R , 3 S , 4 R , 5 R ) -5- (6-amino-9 H -purin-9-yl) -4-hydroxy-3- (phosphonooxy) tetrahydro-2-furanyl] methyl-3 -hydroxy-2,2-dimethyl-4-oxo-4 - ({3-oxo-3 - [(2-sulfanylethyl) amino] propyl} amino) butyl dihydrogen diphosphate ( IUPAC )
  • CoA
Molecular formula C 21 H 36 N 7 O 16 P 3 S
Brief description

beige solid

External identifiers / databases
CAS number
  • 85-61-0
  • 55672-92-9 (sodium salt hydrate)
EC number 201-619-0
ECHA InfoCard 100.001.472
PubChem 6816
ChemSpider 6557
DrugBank DB01992
Wikidata Q407635
properties
Molar mass 767.53 g mol −1
Physical state

firmly

safety instructions
GHS labeling of hazardous substances
no GHS pictograms
H and P phrases H: no H-phrases
P: no P-phrases
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Coenzyme A (also Coenzyme A , CoA or CoASH for short ) is a coenzyme that is used to "activate" alkanoic acids and their derivatives and is directly involved in lipid metabolism and indirectly in sugar and protein metabolism .

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

Isolation was first achieved in 1951 by the German biochemist and later Nobel Prize winner Feodor Lynen in the form of acetyl-coenzyme A ("activated acetic acid") from yeast cells. The structure was cleared up two years later by James Baddiley from the British Lister Institute of Preventive Medicine and Fritz Albert Lipmann from Harvard University .

structure

The coenzyme A molecule is made up of several components: these include a nucleotide ( adenosine diphosphate , ADP), a vitamin ( pantothenic acid , vitamin B5) and an amino acid ( cysteine ), which are linked together during synthesis in the body and then lightly be modified.

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

Structural components in coenzyme A.

β-alanine ( 4 ) and pantoic acid ( 3 ) together are also known as pantothenic acid. If one considers this together with the cysteamine ( 5 ), one speaks of the pantethein ( 5 + 4 + 3 ). 3'-phospho-adenosine can be understood together with the diphosphate as 3'-phospho-adenosine diphosphate. Accordingly, coenzyme A consists of pantethein and 3'-phospho-ADP.

Structural model of coenzyme A.

biosynthesis

The synthesis in the animal organism starts from the essential pantothenic acid, to which a phosphoryl group is first bound with the help of pantothenate kinase and then a cysteine ​​is bound with the help of phosphopantothenate cysteine ​​ligase . After the cysteine ​​has been decarboxylated to cysteamine by the phosphopantothenoylcysteine decarboxylase, an adenosine monophosphate (AMP) is attached to the phosphate group and finally the adenosine is phosphorylated at the 3'-OH group. The last two steps are catalyzed by different domains of the coenzyme A synthase .

For the detailed processes during the synthesis including structural formulas, see the section Web links.

function

Coenzyme A is able to enter into high- energy compounds via the SH group (thiol group) of the cysteamine component. It enters into these compounds with the carboxy groups (-COOH) of alkanoic and fatty acids to form so-called thioester bonds .

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

It is said that coenzyme A activates the binding partners by forming the high-energy thioester bond, because only then are they able to enter into certain chemical reactions in the body at sufficient speed. Without coenzyme A, the binding partners would be significantly less reactive.

Acetyl-CoA

Abstract of the structural formula of Acetyl-CoA

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

Acetyl-CoA is produced in the organism during several metabolic processes:

  • On the one hand, it is formed by the so-called oxidative decarboxylation of pyruvate , which in turn is the end product of glycolysis , but also by the breakdown of amino acids (such as L-alanine ). The oxidative decarboxylation of pyruvate takes place in the mitochondrion . There the pyruvate dehydrogenase enzyme complex catalyzes the splitting off of carbon dioxide CO 2 (the carboxy group is split off, hence “decarboxylation”) and at the same time the linkage of the remaining acetyl residue with the SH group of coenzyme A. The originally central carbon atom of the pyruvate is oxidized (hence "oxidative").
  • In addition, acetyl-CoA is formed during the breakdown of fatty acids in the course of β-oxidation . Here, two carbon atoms in the form of acetyl-CoA are split off from the fatty acid one after the other. So z. B. in the degradation of palmitic acid with 16 carbon atoms in the context of β-oxidation eight molecules of acetyl-CoA. This process also takes place in the mitochondrial matrix.

The acetyl-CoA formed can be completely broken down in the mitochondrion by the citric acid cycle and respiratory chain to CO 2 and H 2 O or it can be used again for the synthesis of high-energy compounds such as triglycerides , ketone bodies or cholesterol . These anabolic processes sometimes take place in the cytosol (e.g. fatty acid synthesis ), but the acetyl-CoA cannot easily leave the mitochondrion and the transport routes for longer-chain carboxylic acids (see below) are also blocked. For the transport of acetyl-CoA from the mitochondrion into the cytosol there is therefore a special transport system, the so-called citrate shuttle .

Acyl-CoA

Acyl-Coenzyme A (acyl-CoA for short) is the name for an "activated" fatty acid . Analogous to acetyl-CoA, instead of an acetyl residue, the residue of a fatty acid - an acyl residue - is attached to the SH group.

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

Acyl-CoA is formed by the enzyme acyl-CoA synthetase (also called thiokinase), which takes place in the cytosol . First of all, the free fatty acid on the carboxy group (-COOH) reacts with ATP , splitting off diphosphate . The so-called acyl adenylate is formed. The energy from this bond is then used to esterify the coenzyme A with the fatty acid, thereby splitting off AMP . Both steps are catalyzed by thiokinase.

To break down fatty acids, the acyl-CoA must be transported into the mitochondria. Like acetyl-CoA, acyl-CoA cannot cross the inner mitochondrial membrane by itself and is transferred to L- carnitine for transport . From this form of transport called acyl-carnitine, the acyl residue in the mitochondria is transferred back to a coenzyme A, so that acyl-CoA is again present.

Fatty alcohols are formed from acyl-CoA, which are used, for example, for the synthesis of beeswax by the honeybees .

Propionyl-CoA

Structure of propionyl-CoA

Propionyl-CoA is produced on several occasions in the metabolism. The best known way is the breakdown ( β-oxidation ) of odd-numbered fatty acids . After repeated cleavage 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 remains at the end. Propionyl-CoA is also formed when fatty acids with methyl branches are broken down. This also applies to the breakdown of the branched side chain of cholesterol , as takes place during the biosynthesis of bile acids - propionyl-CoA is also split off. A very important source of propionyl-CoA is the breakdown of the amino acids isoleucine , valine and methionine as well as the main breakdown pathway of threonine .

Propionyl-CoA is converted to succinyl-CoA , which can then enter the citric acid cycle and help replenish it . For this purpose, propionyl-CoA is first converted into D- methylmalonyl-CoA by the biotin- dependent propionyl-CoA carboxylase . The methylmalonyl-CoA epimerase then generates the L isomer. This in turn is converted into succinyl-CoA by methylmalonyl-CoA mutase , whose function depends on cobalamin .

Propionyl-CoA also plays a role in fatty acid synthesis . The formation of odd-numbered fatty acids starts with propionyl-CoA. Methyl branches within a fatty acid chain can be created by chain extension with methylmalonyl-CoA, which is produced from propionyl-CoA by propionyl-CoA carboxylase.

Individual evidence

  1. a b c d Data sheet Coenzyme A hydrate, ≥85% (UV, HPLC) from Sigma-Aldrich , accessed on April 18, 2017 ( PDF ).
  2. Janine Hellenbrand: Characterization of acyl-CoA reductases . Dissertation, RWTH Aachen, 2012.
  3. ^ D. Doenecke, J. Koolman, G. Fuchs, W. Gerok: Karlsons Biochemie und Pathobiochemie. 15th edition. Georg Thieme Verlag, Stuttgart 2005; Pp. 214f, 219ff, 281, 328f ISBN 978-3-13-357815-8 .
  4. Entry EC  5.1.99.1 in the BRENDA enzyme database
  5. JM Berg, JL Tymoczko, L. Stryer: Biochemistry. 6th edition. Spectrum Academic Publishing House, Elsevier GmbH, Munich 2007; Pp. 697f, 741f, 744f; ISBN 978-3-8274-1800-5 .
  6. K. Urich: Comparative Animal Biochemistry. Springer Verlag, Berlin 1994; P. 564f; ISBN 3-540-57420-4 .

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Web links

Commons : Coenzyme A  - Collection of pictures, videos and audio files
Wikibooks: Biosynthesis of Coenzyme A  - Learning and Teaching Materials