ATP citrate lyase
| ATP citrate lyase | |
|---|---|
| File:Atpcitratelyase.pdb.png Crystal structure of truncated human ATP-citrate lyase.[1] | |
| Identifiers | |
| Symbol | ACLY |
| Entrez | 47 |
| HUGO | 115 |
| OMIM | 108728 |
| RefSeq | NM_001096 |
| UniProt | P53396 |
| Other data | |
| EC number | 2.3.3.8 |
| Locus | Chr. 17 q21.2 |
ATP citrate lyase is an enzyme that in animals represents an important step in fatty acid biosynthesis.[2] ATP citrate lyase is important in that, by converting citrate to acetyl CoA, it links the metabolism of carbohydrates, which yields citrate as an intermediate, and the production of fatty acids, which requires acetyl CoA.[1] In plants, ATP citrate lyase generates cytosolic acetyl-CoA precursor of thousands of specialized metabolites including waxes, sterols, and polyketides.[3]
Function
ATP citrate lyase is the primary enzyme responsible for the synthesis of cytosolic acetyl-CoA in many tissues. The enzyme is a tetramer of apparently identical subunits. The product, acetyl-CoA, in animals serves several important biosynthetic pathways, including lipogenesis and cholesterogenesis.[4] It is activated by insulin.[5] In plants, ATP citrate lyase generates the acetyl-CoA for cytosolically-synthesized metabolites. (Acetyl-CoA is not transported across subcellular membranes of plants.) These include: elongated fatty acids (used in seed oils, membrane phospholipids, the ceramide moiety of sphingolipids, cuticle, cutin, and suberin); flavonoids; malonic acid; acetylated phenolics, alkaloids, isoprenoids, anthocyanins, and sugars; and, mevalonate-derived isoprenoids (e.g., sesquiterpenes, sterols, brassinosteroids); malonyl and acyl-derivatives (d-amino acids, malonylated flavonoids, acylated, prenylated and malonated proteins).[3] De novo fatty acid biosynthesis in plants is plastidic, thus ATP citrate lyase is not important for this pathway.
ATP-citrate lyase is responsible for catalyzing the conversion of citrate and CoA into acetyl-CoA and oxaloacetate, along with the hydrolysis of ATP.[1]
Reaction
In the presence of ATP and Coenzyme A, citrate lyase catalyzes the cleavage of citrate to yield acetyl CoA, oxaloacetate, ADP, and orthophosphate:
- citrate + ATP + CoA → oxaloacetate + Acetyl-CoA + ADP + Pi
This enzyme was formerly listed as EC 4.1.3.8.[6]
Location
The enzyme is cytosolic in plants[3] and animals.
Structure
The enzyme is composed of two subunits in green plants (including Chlorophyceae, Marchantimorpha, Bryopsida, Pinaceae, monocotyledons, and eudicots), species of fungi, Glaucophytes, Chlamydomonas, and prokaryotes.
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.[3]
A structure of truncated human ATP citrate lyase was determined using X-ray diffraction to a resolution of 2.10 Å. [1]
References
- ↑ 1.0 1.1 1.2 1.3 PDB: 3MWE; Sun T, Hayakawa K, Bateman KS, Fraser ME (August 2010). "Identification of the citrate-binding site of human ATP-citrate lyase using X-ray crystallography". J. Biol. Chem. 285 (35): 27418–27428. doi:10.1074/jbc.M109.078667. PMC 2930740. PMID 20558738.
- ↑ Elshourbagy NA, Near JC, Kmetz PJ, Wells TN, Groot PH, Saxty BA, Hughes SA, Franklin M, Gloger IS (March 1992). "Cloning and expression of a human ATP-citrate lyase cDNA". Eur. J. Biochem. 204 (2): 491–499. doi:10.1111/j.1432-1033.1992.tb16659.x. PMID 1371749. Archived from the original on 2013-01-18.
- ↑ 3.0 3.1 3.2 3.3 Fatland BL, Ke J, Anderson MD, Mentzen WI, Cui LW, Allred CC, Johnston JL, Nikolau BJ, Wurtele ES (October 2002). "Molecular characterization of a heteromeric ATP-citrate lyase that generates cytosolic acetyl-coenzyme A in Arabidopsis". Plant Physiol. 130 (2): 740–756. doi:10.1104/pp.008110. PMC 166603. PMID 12376641.
- ↑ "Entrez Gene: ATP citrate lyase".
- ↑ Guay C, Madiraju SR, Aumais A, Joly E, Prentki M (December 2007). "A role for ATP-citrate lyase, malic enzyme, and pyruvate/citrate cycling in glucose-induced insulin secretion". J. Biol. Chem. 282 (49): 35657–35665. doi:10.1074/jbc.M707294200. PMID 17928289.
- ↑ ATP+Citrate+Lyase at the US National Library of Medicine Medical Subject Headings (MeSH)
Further reading
- Lovell SC, Davis IW, Arendall WB, de Bakker PI, Word JM, Prisant MG, Richardson JS, Richardson DC (February 2003). "Structure validation by Calpha geometry: phi,psi and Cbeta deviation". Proteins. 50 (3): 437–450. doi:10.1002/prot.10286. PMID 12557186.
External links
- ATP Citrate Lyase at the US National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
Ramachandran Plot of ATP Citrate Lyase https://web.archive.org/web/20121019183028/http://www.rcsb.org/pdb/images/3MWD_ram_m_500.pdf
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