Aconitate decarboxylase explained

aconitate decarboxylase
Ec Number:	4.1.1.6
Cas Number:	9025-01-8
Go Code:	0047613

The enzyme aconitate decarboxylase (i.e., ACOD1, also termed cis-aconitate decarboxylase, immune-responsive gene 1, immune response gene 1, and IRK1^{[1] [2]}) is a protein enzyme that in humans is encoded by the gene located at position 22.3 on the long arm (i.e., p-arm) of chromosome 13.^[3] ACOD1 catalyzes the following reversible (i.e., runs in both directions, as indicated by

\rightleftharpoons ) decarboxylation chemical reaction:^{[4] [5] [6]}

cis-aconitate

\rightleftharpoons itaconate + CO₂

Hence, ACOD1 converts cis-aconitate into two products, itaconate and CO₂ or itaconate and CO₂ into one product, aconitate.

ACOD1 belongs to the family of lyases, specifically the carboxy-lyases, which cleave carbon-carbon bonds. The systematic name of this enzyme class is cis-aconitate carboxy-lyase (itaconate-forming). Other names once in common use for this enzyme class include CAD and cis-aconitate carboxy-lyase. ACOD1 participates in c5-branched dibasic acid metabolism.^[7]

Ustilago maydis (a species of Ustilago fungi) converts cis-aconitate to its thermodynamically favored product, trans-aconitate, by the enzyme aconitate delta-isomerase (i.e., Adi1). The trans-aconitate product is decarboxylated to itaconate by trans-aconitate decarboxylase (i.e., Tad1).^[8] This Adi followed by Tad 1 enzymatic metabolic pathway is:

cis-aconitate

\rightleftharpoons trans-itaconate → itaconate + CO₂

Trans-aconitate decarboxylase does not metabolize cis-aconitate to itaconate.^[8] (The genes for aconitate delta-isomerase and trans-aconitate decarboxylase have been reported in several types of fungi hut not in other organisms, including humand, and are classified as provisional, i.e., accepted provisional to further studies.)

References

• BENTLEY R, THIESSEN CP . 1957 . Biosynthesis of itaconic acid in Aspergillus terreus. III. The properties and reaction mechanism of cis-aconitic acid decarboxylase . J. Biol. Chem. . 226 . 703 - 20 . 13438855 . 2 . 10.1016/S0021-9258(18)70852-1 . free .

Notes and References

1. Dalla Pozza E, Dando I, Pacchiana R, Liboi E, Scupoli MT, Donadelli M, Palmieri M . Regulation of succinate dehydrogenase and role of succinate in cancer . Seminars in Cell & Developmental Biology . 98 . 4–14 . February 2020 . 31039394 . 10.1016/j.semcdb.2019.04.013 .
2. Singh S, Singh PK, Jha A, Naik P, Joseph J, Giri S, Kumar A . Integrative metabolomics and transcriptomics identifies itaconate as an adjunct therapy to treat ocular bacterial infection . Cell Reports. Medicine . 2 . 5 . 100277 . May 2021 . 34095879 . 8149370 . 10.1016/j.xcrm.2021.100277 .
3. Liu X, Zhang L, Wu XP, Zhu XL, Pan LP, Li T, Yan BY, Xu AQ, Li H, Liu Y . Polymorphisms in IRG1 gene associated with immune responses to hepatitis B vaccination in a Chinese Han population and function to restrain the HBV life cycle . Journal of Medical Virology . 89 . 7 . 1215–1223 . July 2017 . 28004399 . 10.1002/jmv.24756 .
4. Peace CG, O'Neill LA . The role of itaconate in host defense and inflammation . The Journal of Clinical Investigation . 132 . 2 . January 2022 . 35040439 . 8759771 . 10.1172/JCI148548 .
5. Wu KK . Extracellular Succinate: A Physiological Messenger and a Pathological Trigger . International Journal of Molecular Sciences . 24 . 13 . July 2023 . 11165 . 37446354 . 10342291 . 10.3390/ijms241311165 . free .
6. Elkasaby T, Hanh DD, Kawaguchi H, Kondo A, Ogino C . Effect of different metabolic pathways on itaconic acid production in engineered Corynebacterium glutamicum . Journal of Bioscience and Bioengineering . 136 . 2 . 109–116 . August 2023 . 37328405 . 10.1016/j.jbiosc.2023.05.006 .
7. Nie Z, Wang L, Zhao P, Wang Z, Shi Q, Liu H . Metabolomics reveals the impact of nitrogen combined with the zinc supply on zinc availability in calcareous soil via root exudates of winter wheat (Triticum aestivum) . Plant Physiology and Biochemistry . 204 . 108069 . November 2023 . 37852066 . 10.1016/j.plaphy.2023.108069 .
8. Geiser E, Przybilla SK, Friedrich A, Buckel W, Wierckx N, Blank LM, Bölker M . Ustilago maydis produces itaconic acid via the unusual intermediate trans-aconitate . Microbial Biotechnology . 9 . 1 . 116–26 . January 2016 . 26639528 . 4720413 . 10.1111/1751-7915.12329 .