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Citrate metabolism

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).


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Citrate is the first product of the tricarboxylic acid cycle (TCA cycle), and this mitochondrially produced citrate is moved into the cytosol by the transporter SLC25A1. Citrate in the circulation is transported into cells by SLC13A5. A third source of citrate is that produced intracellularly by isocitrate dehydrogenase 1 (IDH1) from α-ketoglutarate (arising from glutamine metabolism) under conditions of hypoxic stress for example. ATP-citrate lyase (ACLY) converts cytosolic citrate into acetyl-CoA which is then utilised for lipogenesis. Targeting citrate transport and/or synthesis are mechanisms being explored for lipid-lowering potential and application to the treatment of chronic metabolic diseases that are characterised by dysregulated lipogenesis. Inhibition of IDH activity has been directed towards anti-tumour drug development, with two IDH inhibitors already in clinical use.


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ACLY (ATP citrate lyase) Show summary »

Target Id 3245
Nomenclature ATP citrate lyase
Common abbreviation ACLY
Genes ACLY (Hs), Acly (Mm), Acly (Rn)
Ensembl ID ENSG00000131473 (Hs), ENSMUSG00000020917 (Mm), ENSRNOG00000016924 (Rn)
UniProtKB AC P53396 (Hs), Q91V92 (Mm), ACLY_RAT (Rn)
EC number
NDI-091143 pKd 8.1 [3]
bempedoic acid pKi 5.7 [4]
NDI-091143 pIC50 8.7 [3]
BMS-303141 pIC50 6.9 [2]
Comment ACLY catalyzes the conversion of cytosolic citrate and coenzyme A to oxaloacetate (OAA) and acetyl coenzyme A (acetyl-CoA). Acetyl-CoA is required for fatty acid (lipid) synthesis. ACLY is considered to be a tractable target for the development of therapeutics for metabolic diseases. Based on its role in the metabolic reprogramming in cancers, it is also an oncology drug target.

isocitrate dehydrogenase (NADP(+)) 1 / IDH1 C Show summary » More detailed page go icon to follow link


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How to cite this family page

Database page citation:

Citrate metabolism. Accessed on 06/12/2023. IUPHAR/BPS Guide to PHARMACOLOGY,

Concise Guide to PHARMACOLOGY citation:

Alexander SP, Fabbro D, Kelly E, Mathie A, Peters JA, Veale EL et al. (2021) THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: Enzymes. Br J Pharmacol. 178 Suppl 1:S313-S411.