ATP citrate lyase
| ATP citrate lyase | ||
|---|---|---|
|
||
| Properties of human protein | ||
| Mass / length primary structure | 1101 amino acids | |
| Secondary to quaternary structure | Homotetramer | |
| Cofactor | magnesium | |
| Identifier | ||
| Gene name | ACLY | |
| External IDs | ||
| Enzyme classification | ||
| EC, category | 2.3.3.8 , Transferase | |
| Response type | Transfer of an acetyl group | |
| Substrate | ATP + citrate + CoA | |
| Products | ADP + oxaloacetate + acetyl-CoA + P i | |
| Occurrence | ||
| Homology family | ACLY | |
| Parent taxon | Eukaryotes | |
ATP citrate lyase (also: ATP citrate synthase ) is the enzyme that transfers an acetyl group from citrate to coenzyme A in the cytosol of eukaryotic cells , resulting in acetyl-CoA . This is the second reaction step in the citrate shuttle , which is necessary in order to transport the acetyl-CoA produced during oxidative decarboxylation out of the mitochondria . These processes are part of the energy metabolism in all eukaryotes .
The acetyl-CoA produced is the starting material for the lipogenesis that takes place in the cytosol .
Hypocitraturia is a cause of kidney stones and can be caused by an excessive activity of ATP citrate lyase in urinary leukocytes , as found in a Thai study. Dietary changes or potassium citrate supplementation are possible therapies. ATP citrate lyase is a potential target for fighting cancer . In a phase 3 study, an inhibitor of ATP citrate lyase, bempedoic acid , further reduced LDL levels in combination therapy with statins than statins alone. A market approval for bempedoic acid is expected in 2020.
Catalyzed reaction
+ CoA-SH + ATP ⇒
⇒ 
+ 
+ ADP + P i
An acetyl residue is transferred from citrate to CoA with the consumption of ATP: oxaloacetate and acetyl-CoA are formed.
Individual evidence
- ↑ UniProt P53396
- ↑ Tosukhowong P, Borvonpadungkitti S, Prasongwatana V, et al : Urinary citrate excretion in patients with renal stone: roles of leucocyte ATP citrate lyase activity and potassium salts therapy . In: Clin. Chim. Acta . 325, No. 1-2, November 2002, pp. 71-8. PMID 12367768 .
- ↑ Hatzivassiliou G, Zhao F, Bauer DE, et al : ATP citrate lyase inhibition can suppress tumor cell growth . In: Cancer Cell . 8, No. 4, October 2005, pp. 311-21. doi : 10.1016 / j.ccr.2005.09.008 . PMID 16226706 .
- ↑ Migita T, Narita T, Nomura K, et al : ATP citrate lyase: activation and therapeutic implications in non-small cell lung cancer . In: Cancer Res . . 68, No. 20, October 2008, pp. 8547-54. doi : 10.1158 / 0008-5472.CAN-08-1235 . PMID 18922930 .
- ↑ Ray KK, Bays HE, Catapano AL, et al : Safety and efficacy of bempedoic acid to reduce LEL cholesterol . In: N. Engl. J. Med. . 380, No. 11, March 2019, pp. 1022-1032. doi : 10.1056 / NEJMoa1803917 .
Web links
- Gopinathrao / reactome.org: Generation of Cytoplasmic Acetyl CoA from Citrate