ATP citrate lyase
Encyclopedia
ATP citrate lyase is an enzyme
that represents an important step in fatty acid biosynthesis. This step in fatty acid biosynthesis occurs because ATP citrate lyase is the link between the metabolism of carbohydrates (which causes energy) to the production of fatty acids.
in many tissues. The enzyme is a tetramer of apparently identical subunits. The product, acetyl-CoA, serves several important biosynthetic pathways, including lipogenesis
and cholesterogenesis. It is activated by insulin. ATP-citrate lyase is also responsible for catalyzing the conversion of citrate
and CoA
into acetyl-CoA
and oxaloacetate, along with the hydrolysis of ATP.
and Coenzyme A
, citrate lyase catalyzes the cleavage of citrate
to yield acetyl CoA, oxaloacetate, ADP
, and orthophosphate:
This enzyme was formerly listed as EC 4.1.3.8.
, Marchantimorpha, Bryopsida
, Pinaceae
, monocotyledon
s, and eudicots), species of fungi, Glaucophyte
s, Chlamydomonas
, and prokaryote
s.
Animal ACL enzymes are homomeric, presumably an evolutionary fusion of the ACLA and ACLB genes probably occurred early in the evolutionary history of this kingdom.
A structure of human ATP citrate lyase was determined using X-ray diffraction to a resolution of 2.10 Å. The enzyme is composed of two polymer chains which are polypeptides. Chain A of the first polymer is 425 amino acids in length. Chain B of the second polymer is 334 amino acids in length.
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
that represents an important step in fatty acid biosynthesis. This step in fatty acid biosynthesis occurs because ATP citrate lyase is the link between the metabolism of carbohydrates (which causes energy) to the production of fatty acids.
Function
ATP citrate lyase is the primary enzyme responsible for the synthesis of cytosolic acetyl-CoAAcetyl-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...
in many tissues. The enzyme is a tetramer of apparently identical subunits. The product, acetyl-CoA, serves several important biosynthetic pathways, including lipogenesis
Lipogenesis
Lipogenesis is the process by which acetyl-CoA is converted to fats. The former is an intermediate stage in metabolism of simple sugars, such as glucose, a source of energy of living organisms. Through lipogenesis, the energy can be efficiently stored in the form of fats...
and cholesterogenesis. It is activated by insulin. ATP-citrate lyase is also responsible for catalyzing the conversion of citrate
Citrate
A citrate can refer either to the conjugate base of citric acid, , or to the esters of citric acid. An example of the former, a salt is trisodium citrate; an ester is triethyl citrate.-Other citric acid ions:...
and CoA
COA
COA can refer to:*Codename Amscray*Cash on Arrival*Cause of action*CedarOpenAccounts*Center of Attention*Certificate of Appealability*Certificate of Approval for marriage or civil partnership in the United Kingdom*Certificate of Authenticity...
into 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...
and oxaloacetate, along with the hydrolysis of ATP.
Reaction
In the presence of ATPAdenosine 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...
and Coenzyme A
Coenzyme A
Coenzyme A is a coenzyme, notable for its role in the synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle. All sequenced genomes encode enzymes that use coenzyme A as a substrate, and around 4% of cellular enzymes use it as a substrate...
, citrate lyase catalyzes the cleavage of citrate
Citrate
A citrate can refer either to the conjugate base of citric acid, , or to the esters of citric acid. An example of the former, a salt is trisodium citrate; an ester is triethyl citrate.-Other citric acid ions:...
to yield acetyl CoA, oxaloacetate, ADP
Adenosine diphosphate
Adenosine diphosphate, abbreviated ADP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside adenosine. ADP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase adenine....
, and orthophosphate:
- citrate + ATP + CoA + H2O-->oxaloacetate + 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...
+ ADP + Pi.
This enzyme was formerly listed as EC 4.1.3.8.
Structure
The enzyme is composed of two subunits in green plants (including ChlorophyceaeChlorophyceae
The Chlorophyceae are one of the classes of green algae, distinguished mainly on the basis of ultrastructural morphology. For example the chlorophycean CW clade, and chlorophycean DO clade, are defined by the arrangement of their flagella. Members of the CW clade have flagella that are displaced...
, Marchantimorpha, Bryopsida
Bryopsida
The Bryopsida constitute the largest class of mosses, containing 95% of all moss species. It consists of approximately 11,500 species, common throughout the whole world....
, Pinaceae
Pinaceae
Pinaceae are trees or shrubs, including many of the well-known conifers of commercial importance such as cedars, firs, hemlocks, larches, pines and spruces. The family is included in the order Pinales, formerly known as Coniferales. Pinaceae are supported as monophyletic by its protein-type sieve...
, monocotyledon
Monocotyledon
Monocotyledons, also known as monocots, are one of two major groups of flowering plants that are traditionally recognized, the other being dicotyledons, or dicots. Monocot seedlings typically have one cotyledon , in contrast to the two cotyledons typical of dicots...
s, and eudicots), species of fungi, Glaucophyte
Glaucophyte
The glaucophytes, also known as glaucocystophytes or glaucocystids, are a small group of freshwater microscopic algae. Together with the red algae and green algae plus land plants , they form the Archaeplastida...
s, Chlamydomonas
Chlamydomonas
Chlamydomonas is a genus of green algae. They are unicellular flagellates. Chlamydomonas is used as a model organism for molecular biology, especially studies of flagellar motility and chloroplast dynamics, biogenesis, and genetics...
, and prokaryote
Prokaryote
The prokaryotes are a group of organisms that lack a cell nucleus , or any other membrane-bound organelles. The organisms that have a cell nucleus are called eukaryotes. Most prokaryotes are unicellular, but a few such as myxobacteria have multicellular stages in their life cycles...
s.
Animal ACL enzymes are homomeric, presumably an evolutionary fusion of the ACLA and ACLB genes probably occurred early in the evolutionary history of this kingdom.
A structure of human ATP citrate lyase was determined using X-ray diffraction to a resolution of 2.10 Å. The enzyme is composed of two polymer chains which are polypeptides. Chain A of the first polymer is 425 amino acids in length. Chain B of the second polymer is 334 amino acids in length.