Caenorhabditis elegans and Ascaris suum: Inhibition of isocitrate lyase by itaconate

Patel, Thakor R.; McFadden, Bruce A.

doi:10.1016/0014-4894(78)90107-8

Cited by 41 publications

(36 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The apparent Ki was 7 ,LIM at pH 7.7 at 30 C (25). Under corresponding conditions the Ki values for two nematode enzymes, both of which were inhibited noncompetitively, were 7 and 19 ,lM (17). The flax enzyme is similarly inhibited (Ki = 17 ,iM at pH 7.6, 30 C).…”

Section: Discussionmentioning

confidence: 78%

See 1 more Smart Citation

Enzyme Profiles in Seedling Development and the Effect of Itaconate, an Isocitrate Lyase-directed Reagent

Khan¹,

McFadden²

1979

Plant Physiol.

Self Cite

View full text Add to dashboard Cite

Changes in levels of isocitrate lyase, malate synthase, and catalase have been investigated during germination of flax (Liu,m usitatissiumn L.) in the presence and absence of itaconate. Germination was accompanied by a rapid increase in these enzymes during the first 3 days. The presence of 38 miHmolar itaconate inhibited the incidence of seed germination and the growth of embryo axes as well as Plant Materials. The following were used: flax (Linum usitatissimum), corn (Zea mays), soybean (Glycine hispida), green gram (Vigna glabra), black eyed bean (Vigna sinensis), fenugreek (Trigonella foenumgraecum), alfalfa (Medicago sativa), lentil (Lens culinaris), and wheat (Triticum aestivum L.).Germination and Seedling Growth. Flax seeds variety Varansi local from an Indian cultivar was used for detailed studies. Seeds were germinated essentially as described by Khan et al. (9). Seeds were surface-sterilized for 5 s in 0.01% (w/v) HgCl2 solution, washed with sterile distilled H20, and transferred to sterile Petri dishes lined with moistened filter paper and incubated at 25 C.For the treatment with itaconate, seeds were soaked in an appropriate concentration of the inhibitor for 6 h at 4 C, and the seeds then transferred to Petri dishes containing 10 ml of test solution. Respective controls received the same treatment, except that water was used instead of inhibitor solution. The zero time of the germination period in all of these experiments was 6 h after the initiation of seed imbibition. In separate experiments we have shown that no marked change in enzyme activities was observed during the imbibition period at 4 C. For enzyme assays done on seeds incubated in the presence or absence of itaconate, seeds were selected at random prior to germination. Postgermination assays were conducted only on seeds in which the embryo axis had emerged.Preparation of Extracts. For the preparation of crude enzyme extract, seedlings were harvested and washed with deionized H20 followed by glass-distilled H20. The

show abstract

Section: Discussionmentioning

confidence: 78%

“…Similar effects of itaconate (14). The function of isocitrate lyase in nematode development has been implied (1,16,17). In recent research on the nematode C. elegans it has been found that 15 mm itaconate almost completely abolishes axenic growth and is much more toxic than oxalate, maleate and succinate (17).…”

Section: Discussionmentioning

confidence: 99%

Enzyme Profiles in Seedling Development and the Effect of Itaconate, an Isocitrate Lyase-directed Reagent

Khan¹,

McFadden²

1979

Plant Physiol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…It has previously been shown that itaconic acid has an antimicrobial activity by inhibiting isocitrate lyase (ICL) (29,30), an enzyme of the glyoxylate shunt (Fig. 6A).…”

Section: Itaconic Acid Is Produced By Human Primary Macrophages But Atmentioning

confidence: 98%

Immune-responsive gene 1 protein links metabolism to immunity by catalyzing itaconic acid production

Michelucci

Cordes

Ghelfi

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

859

922

View full text Add to dashboard Cite

Immunoresponsive gene 1 (Irg1) is highly expressed in mammalian macrophages during inflammation, but its biological function has not yet been elucidated. Here, we identify Irg1 as the gene coding for an enzyme producing itaconic acid (also known as methylenesuccinic acid) through the decarboxylation of cis-aconitate, a tricarboxylic acid cycle intermediate. Using a gain-and-loss-of-function approach in both mouse and human immune cells, we found Irg1 expression levels correlating with the amounts of itaconic acid, a metabolite previously proposed to have an antimicrobial effect. We purified IRG1 protein and identified its cis-aconitate decarboxylating activity in an enzymatic assay. Itaconic acid is an organic compound that inhibits isocitrate lyase, the key enzyme of the glyoxylate shunt, a pathway essential for bacterial growth under specific conditions. Here we show that itaconic acid inhibits the growth of bacteria expressing isocitrate lyase, such as Salmonella enterica and Mycobacterium tuberculosis. Furthermore, Irg1 gene silencing in macrophages resulted in significantly decreased intracellular itaconic acid levels as well as significantly reduced antimicrobial activity during bacterial infections. Taken together, our results demonstrate that IRG1 links cellular metabolism with immune defense by catalyzing itaconic acid production.

show abstract

“…Itaconic acid plays an important role as a bioactive compound in living organisms: Itaconic acid inhibits the glyoxylate shunt essential for many bacteria to survive during infection (59,75). The activation of the glyoxylate shunt is a survival strategy of invading pathogens, allowing them to utilize acetyl-CoA-generating carbon sources such as fatty acids or cholesterol for biomass production under glucose-limiting conditions (51).…”

Section: Itaconic Acid Inhibits the Glyoxylate Shuntmentioning

confidence: 99%

Itaconic Acid: The Surprising Role of an Industrial Compound as a Mammalian Antimicrobial Metabolite

2015

View full text Add to dashboard Cite

Itaconic acid is well known as a precursor for polymer synthesis and has been involved in industrial processes for decades. In a recent surprising discovery, itaconic acid was found to play a role as an immune-supportive metabolite in mammalian immune cells, where it is synthesized as an antimicrobial compound from the citric acid cycle intermediate cis-aconitic acid. Although the immune-responsive gene 1 protein (IRG1) has been associated to immune response without a mechanistic function, the critical link to itaconic acid production through an enzymatic function of this protein was only recently revealed. In this review, we highlight the history of itaconic acid as an industrial and antimicrobial compound, starting with its biotechnological synthesis and ending with its antimicrobial function in mammalian immune cells. 12.1

show abstract

Caenorhabditis elegans and Ascaris suum: Inhibition of isocitrate lyase by itaconate

Cited by 41 publications

References 28 publications

Enzyme Profiles in Seedling Development and the Effect of Itaconate, an Isocitrate Lyase-directed Reagent

Enzyme Profiles in Seedling Development and the Effect of Itaconate, an Isocitrate Lyase-directed Reagent

Immune-responsive gene 1 protein links metabolism to immunity by catalyzing itaconic acid production

Itaconic Acid: The Surprising Role of an Industrial Compound as a Mammalian Antimicrobial Metabolite

Contact Info

Product

Resources

About