Coenzyme A
Encyclopedia
Coenzyme A is a coenzyme, notable for its role in the synthesis and oxidation of fatty acid
s, and the oxidation of pyruvate
in the citric acid cycle
. All sequenced genome
s encode enzymes that use coenzyme A as a substrate, and around 4% of cellular enzymes use it (or a thioester, such as acetyl-CoA
) as a substrate. It is adapted from cysteamine
, pantothenate
, and adenosine triphosphate
.
, it can react with carboxylic acid
s to form thioester
s, thus functioning as an acyl
group carrier. It assists in transferring fatty acid
s from the cytoplasm
to mitochondria. A molecule of coenzyme A carrying an acetyl
group is also referred to as acetyl-CoA
. When it is not attached to an acyl group, it is usually referred to as 'CoASH' or 'HSCoA'.
Coenzyme A is also the source of the phosphopantetheine
group that is added as a prosthetic group to proteins such as acyl carrier protein
and formyltetrahydrofolate dehydrogenase
.
Fatty acid
In chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from...
s, and the oxidation of pyruvate
Pyruvic acid
Pyruvic acid is an organic acid, a ketone, as well as the simplest of the alpha-keto acids. The carboxylate ion of pyruvic acid, CH3COCOO−, is known as pyruvate, and is a key intersection in several metabolic pathways....
in the citric acid cycle
Citric acid cycle
The citric acid cycle — also known as the tricarboxylic acid cycle , the Krebs cycle, or the Szent-Györgyi-Krebs cycle — is a series of chemical reactions which is used by all aerobic living organisms to generate energy through the oxidization of acetate derived from carbohydrates, fats and...
. All sequenced genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
s encode enzymes that use coenzyme A as a substrate, and around 4% of cellular enzymes use it (or a thioester, such as acetyl-CoA
Acetyl-CoA
Acetyl coenzyme A or acetyl-CoA is an important molecule in metabolism, used in many biochemical reactions. Its main function is to convey the carbon atoms within the acetyl group to the citric acid cycle to be oxidized for energy production. In chemical structure, acetyl-CoA is the thioester...
) as a substrate. It is adapted from cysteamine
Cysteamine
Cysteamine is the chemical compound with the formula HSCH2CH2NH2. It is the simplest stable aminothiol and a degradation product of the amino acid cysteine. It is often used as the hydrochloride salt, HSCH2CH2NH3Cl....
, pantothenate
Pantothenic acid
Pantothenic acid, also called pantothenate or vitamin B5 , is a water-soluble vitamin. For many animals, pantothenic acid is an essential nutrient. Animals require pantothenic acid to synthesize coenzyme-A , as well as to synthesize and metabolize proteins, carbohydrates, and fats.Pantothenic acid...
, and adenosine triphosphate
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
.
Biosynthesis
Coenzyme A is synthesized in a five-step process from pantothenate and cysteine:- Pantothenate (vitamin B5) is phosphorylated to 4'-phosphopantothenate by the enzyme pantothenate kinasePantothenate kinasePantothenate kinase is the first enzyme in the Coenzyme A biosynthetic pathway. It phophorylates pantothenate to form 4'-phosphopantothenate.-Types:...
(PanK; CoaA; CoaX) - A cysteineCysteineCysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
is added to 4'-phosphopantothenate by the enzyme phosphopantothenoylcysteine synthetasePhosphopantothenoylcysteine synthetaseHuman phosphopantothenoylcysteine synthetase is a dimer with identical monomers.PPC syththetase converts phosphopantothenate into phosphopantothenoylcysteine by combining with cysteine while using a unit of ATP....
(PPC-DC; CoaB) to form 4'-phospho-N-pantothenoylcysteine (PPC) - PPC is decarboxylated to 4'-phosphopantetheinePantetheinePantetheine is the cysteamine amide analogue of pantothenic acid . The dimer of this compound, pantethine is more commonly known, and is considered to be a more potent form of vitamin B5 than pantothenic acid. Pantetheine is an intermediate in the production of coenzyme A by the body....
by phosphopantothenoylcysteine decarboxylasePhosphopantothenoylcysteine decarboxylaseIn enzymology, a phosphopantothenoylcysteine decarboxylase is an enzyme that catalyzes the chemical reactionHence, this enzyme has one substrate, N-[-4'-phosphopantothenoyl]-L-cysteine, and two products, pantotheine 4'-phosphate and CO2....
(CoaC) - 4'-phosphopantetheinePantetheinePantetheine is the cysteamine amide analogue of pantothenic acid . The dimer of this compound, pantethine is more commonly known, and is considered to be a more potent form of vitamin B5 than pantothenic acid. Pantetheine is an intermediate in the production of coenzyme A by the body....
is adenylylatedAdenineAdenine is a nucleobase with a variety of roles in biochemistry including cellular respiration, in the form of both the energy-rich adenosine triphosphate and the cofactors nicotinamide adenine dinucleotide and flavin adenine dinucleotide , and protein synthesis, as a chemical component of DNA...
to form dephospho-CoA by the enzyme phosphopantetheine adenylyl transferase (CoaD) - Finally, dephospho-CoA is phosphorylated using ATP to coenzyme A by the enzyme dephosphocoenzyme A kinase (CoaE).
Function
Since coenzyme A is, in chemical terms, a thiolThiol
In organic chemistry, a thiol is an organosulfur compound that contains a carbon-bonded sulfhydryl group...
, it can react with carboxylic acid
Carboxylic acid
Carboxylic acids are organic acids characterized by the presence of at least one carboxyl group. The general formula of a carboxylic acid is R-COOH, where R is some monovalent functional group...
s to form thioester
Thioester
Thioesters are compounds with the functional group C-S-CO-C. They are the product of esterification between a carboxylic acid and a thiol. Thioesters are widespread in biochemistry, the best-known derivative being acetyl-CoA.-Synthesis:...
s, thus functioning as an acyl
Acyl
An acyl group is a functional group derived by the removal of one or more hydroxyl groups from an oxoacid, including inorganic acids.In organic chemistry, the acyl group is usually derived from a carboxylic acid . Therefore, it has the formula RCO-, where R represents an alkyl group that is...
group carrier. It assists in transferring fatty acid
Fatty acid
In chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from...
s from the cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
to mitochondria. A molecule of coenzyme A carrying an acetyl
Acetyl
In organic chemistry, acetyl is a functional group, the acyl with chemical formula COCH3. It is sometimes represented by the symbol Ac . The acetyl group contains a methyl group single-bonded to a carbonyl...
group is also referred to as acetyl-CoA
Acetyl-CoA
Acetyl coenzyme A or acetyl-CoA is an important molecule in metabolism, used in many biochemical reactions. Its main function is to convey the carbon atoms within the acetyl group to the citric acid cycle to be oxidized for energy production. In chemical structure, acetyl-CoA is the thioester...
. When it is not attached to an acyl group, it is usually referred to as 'CoASH' or 'HSCoA'.
Coenzyme A is also the source of the phosphopantetheine
Phosphopantetheine
4'-Phosphopantetheine is an essential prosthetic group of acyl carrier protein and peptidyl carrier proteins and aryl carrier proteins derived from Coenzyme A...
group that is added as a prosthetic group to proteins such as acyl carrier protein
Acyl carrier protein
The acyl carrier protein is an important component in both fatty acid and polyketide biosynthesis with the growing chain bound during synthesis as a thiol ester at the distal thiol of a 4'-phosphopantethiene moiety...
and formyltetrahydrofolate dehydrogenase
Formyltetrahydrofolate dehydrogenase
In enzymology, a formyltetrahydrofolate dehydrogenase is an enzyme that catalyzes the chemical reactionThe 3 substrates of this enzyme are 10-formyltetrahydrofolate, NADP+, and H2O, whereas its 4 products are tetrahydrofolate, CO2, NADPH, and H+....
.
List of coenzyme A activated acyl groups
- Acetyl-CoAAcetyl-CoAAcetyl coenzyme A or acetyl-CoA is an important molecule in metabolism, used in many biochemical reactions. Its main function is to convey the carbon atoms within the acetyl group to the citric acid cycle to be oxidized for energy production. In chemical structure, acetyl-CoA is the thioester...
- Propionyl-CoAPropionyl-CoAPropionyl-CoA is a coenzyme A derivative of propionic acid.-Production:There are several different ways in which it is formed:* It is formed as a product of beta-oxidation of odd-chain fatty acids....
- Acetoacetyl-CoA
- Coumaroyl-CoA (used in flavonoidFlavonoidFlavonoids , are a class of plant secondary metabolites....
and stilbenoid biosynthesis) - Acyl derived from dicarboxylic acidDicarboxylic acidDicarboxylic acids are organic compounds that contain two carboxylic acid functional groups. In molecular formulae for dicarboxylic acids, these groups are often written as HOOC-R-COOH, where R may be an alkyl, alkenyl, alkynyl, or aryl group...
s- Malonyl-CoAMalonyl-CoAMalonyl-CoA is a coenzyme A derivative.-Functions:It plays a key role in chain elongation in fatty acid biosynthesis and polyketide biosynthesis....
- Succinyl-CoASuccinyl-CoASuccinyl-Coenzyme A, abbreviated as Succinyl-CoA or SucCoA, is a combination of succinic acid and coenzyme A.-Source:It is an important intermediate in the citric acid cycle, where it is synthesized from α-Ketoglutarate by α-ketoglutarate dehydrogenase through decarboxylation...
(used in hemeHemeA heme or haem is a prosthetic group that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin. Not all porphyrins contain iron, but a substantial fraction of porphyrin-containing metalloproteins have heme as their prosthetic group; these are...
biosynthesis) - Hydroxymethylglutaryl-CoA (used in isoprenoid biosynthesis)
- Pimelyl-CoA (used in biotinBiotinBiotin, also known as Vitamin H or Coenzyme R, is a water-soluble B-complex vitamin discovered by Bateman in 1916. It is composed of a ureido ring fused with a tetrahydrothiophene ring. A valeric acid substituent is attached to one of the carbon atoms of the tetrahydrothiophene ring...
biosynthesis) - fatty acyl-CoA (activated form of all fatty acids; only the CoA esters are substrates for important reactions such as mono-, di-, and triacylglycerol synthesis, carnitine palmitoyl transferase, and cholesterol esterification)
- Malonyl-CoA
- Benzoyl CoA
- Phenylacetyl CoA
- Butyryl CoA