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

Tricarboxylic acid

A tricarboxylic acid is an organic carboxylic acid whose chemical structure contains three carboxyl functional groups . The best-known example of a tricarboxylic acid is citric acid.-Examples:*Citric acid*Isocitric acid*Aconitic acid...

 that has three carboxylic acid

Carboxylic acid

Carboxylic acids are organic acids characterized by the presence of at least one carboxyl group. The general formula of a carboxylic acid is R-COOH, where R is some monovalent functional group...

 functional group

Functional group

In organic chemistry, functional groups are specific groups of atoms within molecules that are responsible for the characteristic chemical reactions of those molecules. The same functional group will undergo the same or similar chemical reaction regardless of the size of the molecule it is a part of...

s. The compound is an inhibitor of the enzyme aconitase

Aconitase

Aconitase is an enzyme that catalyses the stereo-specific isomerization of citrate to isocitrate via cis-aconitate in the tricarboxylic acid cycle, a non-redox-active process.- Function :...

 and therefore interferes with the Krebs cycle.

Ester

Ester

Esters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...

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

Natural product

A natural product is a chemical compound or substance produced by a living organism - found in nature that usually has a pharmacological or biological activity for use in pharmaceutical drug discovery and drug design...

s such as the mycotoxin

Mycotoxin

A mycotoxin is a toxic secondary metabolite produced by organisms of the fungus kingdom, commonly known as molds. The term ‘mycotoxin’ is usually reserved for the toxic chemical products produced by fungi that readily colonize crops...

s fumonisin B1 and B2 and AAL toxin T_A and in macrocyclic inhibitors of Ras farnesyl-protein transferase (FPTase) like actinoplanic acid.

It can be synthesized in two steps from fumaric acid

Fumaric acid

Fumaric acid or trans-butenedioic acid is the chemical compound with the formula HO2CCH=CHCO2H. This white crystalline compound is one of two isomeric unsaturated dicarboxylic acids, the other being maleic acid. In fumaric acid the carboxylic acid groups are trans and in maleic acid they are cis...

.

Mechanism of the inhibition of Aconitase

Aconitase normally catalyses, via Aconitic acid

Aconitic acid

Aconitic acid is an organic acid. The two isomers are cis-aconitic acid and trans-aconitic acid. The conjugate base of cis-aconitic acid, cis-aconitate is an intermediate in the isomerization of citrate to isocitrate in the citric acid cycle...

, the interconversion of citric acid

Citric acid

Citric acid is a weak organic acid. It is a natural preservative/conservative and is also used to add an acidic, or sour, taste to foods and soft drinks...

 into isocitric acid

Isocitric acid

Isocitric acid is a protonated form of isocitrate, which is a substrate of the citric acid cycle. Isocitrate is formed from citrate with the help of the enzyme aconitase, and is acted upon by isocitrate dehydrogenase...

(see figure above). Propane-1,2,3-tricarboxylic acid is very suited to bind to aconitase as it only lacks the hydroxide group compourd to citric acid. On the other hand, as the hydroxide group is essential to proceed from citric acid to aconitic acid, the enzyme is not able to complete the reaction. The enzyme is stuck with a molucule it cannot get rid of.