Propane-1,2,3-tricarboxylic acid, also known as tricarballylic acid, carballylic acid, and β-carboxyglutaric acid, is a

tricarboxylic acid A tricarboxylic acid is an organic carboxylic acid that contain three carboxyl functional groups (−COOH). A well-known example is citric acid. Promient examples Some prominent substituted tricarboxylic acids Citric acid, is used in the c ...

. The compound is an inhibitor of the enzyme

aconitase Aconitase (aconitate hydratase; ) is an enzyme that catalyses the stereochemistry, stereo-specific isomerization of citrate to isocitrate via ''cis''-aconitate in the tricarboxylic acid cycle, a non-redox-active process. Image:Citrate wpmp.p ...

and therefore interferes with the

Krebs cycle The citric acid cycle—also known as the Krebs cycle, Szent–Györgyi–Krebs cycle, or TCA cycle (tricarboxylic acid cycle)—is a series of biochemical reactions that release the energy stored in nutrients through acetyl-CoA oxidation. The e ...

Ester In chemistry, an ester is a compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds contain a distin ...

s of propane-1,2,3-tricarboxylic acid are found in

natural product A natural product is a natural compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural products can also be prepared by chemical s ...

s such as the

mycotoxin A mycotoxin (from the Greek μύκης , "fungus" and τοξικός , "poisonous") is a toxic secondary metabolite produced by fungi and is capable of causing disease and death in both humans and other animals. The term 'mycotoxin' is usually rese ...

fumonisin The fumonisins are a group of mycotoxins derived from ''Fusarium'' and their Liseola section. They have strong structural similarity to sphinganine, the backbone precursor of sphingolipids. More specifically, it can refer to: * Fumonisin B1 ...

s B1 and B2 and AAL toxin T_A, and in macrocyclic inhibitors of Ras farnesyl-protein transferase (FPTase) such as actinoplanic acid. Propane-1,2,3-tricarboxylic acid can be synthesized in two steps from

fumaric acid Fumaric acid or ''trans''-butenedioic acid is an organic compound with the formula HO2CCH=CHCO2H. A white solid, fumaric acid occurs widely in nature. It has a fruit-like taste and has been used as a food additive. Its E number is E297. The sa ...

Mechanism of the inhibition of aconitase

Image:Citrate wpmp.png, Image:Aconitic acid.svg, Image:isocitric acid.svg, {{center,

Isocitric acid Isocitric acid is a structural isomer of citric acid. Since citric acid and isocitric acid are structural isomers, they share similar physical and chemical properties. Due to these similar properties, it is difficult to separate the isomers. Salts ...

Aconitase normally catalyses, via the intermediate

aconitic acid Aconitic acid refers to organic compounds with the formula . A white solid, it is classified as a tricarboxylic acid. The two isomers are ''cis''-aconitic acid and ''trans''-aconitic acid. The conjugate base of ''cis''-aconitic acid, ''cis''-aconi ...

, the interconversion of

citric acid Citric acid is an organic compound with the formula . It is a Transparency and translucency, colorless Weak acid, weak organic acid. It occurs naturally in Citrus, citrus fruits. In biochemistry, it is an intermediate in the citric acid cycle, ...

into

isocitric acid Isocitric acid is a structural isomer of citric acid. Since citric acid and isocitric acid are structural isomers, they share similar physical and chemical properties. Due to these similar properties, it is difficult to separate the isomers. Salts ...

. Propane-1,2,3-tricarboxylic acid is well suited to bind to aconitase as it only lacks the hydroxyl group in comparison to citric acid. However, the hydroxyl group is essential to proceed from citric acid to aconitic acid; therefore, the enzyme is not able to complete the reaction with propane-1,2,3-tricarboxylic acid.

References

Tricarboxylic acids Aconitase inhibitors