ATP citrate lyase

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ATP citrate lyase
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
Locus Chr. 17 q21.2

ATP citrate lyase is an enzyme that represents an important step in fatty acid biosynthesis.[2] This step in fatty acid biosynthesis occurs because ATP citrate lyase is the link between the metabolism of carbohydrates (which causes energy) and the production of fatty acids.[1]

Function[edit]

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, serves several important biosynthetic pathways, including lipogenesis and cholesterogenesis.[3] It is activated by insulin.[4] 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.[1]

Reaction[edit]

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 + H2O-->oxaloacetate + Acetyl-CoA + ADP + Pi.

This enzyme was formerly listed as EC 4.1.3.8.[5]

Location[edit]

The enzyme is cytosolic in plants[6] and animals.

Structure[edit]

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.[6]

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.[1]

References[edit]

  1. ^ a b c d 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. 
  2. ^ 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. 
  3. ^ "Entrez Gene: ATP citrate lyase". 
  4. ^ 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. 
  5. ^ ATP Citrate Lyase at the US National Library of Medicine Medical Subject Headings (MeSH)
  6. ^ a b 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. 

Further reading[edit]

  • 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[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.


Ramachandran Plot of ATP Citrate Lyase http://www.rcsb.org/pdb/images/3MWD_ram_m_500.pdf