Production of tricarballylic acid by rumen microorganisms and its potential toxicity in ruminant tissue metabolism

Abstract

1. Rumen microorganisms convert trans-aconitate to tricarballylate. The following experiments describe factors affecting the yield of tricarballylate, its absorption from the rumen into blood and its effect on mammalian citric acid cycle activity in vitro.2. When mixed rumen microorganisms were incubated in vitro with Timothy hay (Phleum praiense L.) and 6.7 mM-trans-aconitate, 64 % of the trans-aconitate was converted to tricarballylate. Chloroform and nirate treatments inhibited methane production and increased the yield of tricarballylate to 82 and 75% respectively. 3. Sheep given gelatin capsules filled with 20 g trans-aconitate absorbed tricarballylate and the plasma concentration ranged from 0.3 to 0.5 mM 9 h after administration. Feeding an additional 40 g potassium chloride had little effect on plasma tricarballylate concentrations. Between 9 and 36 h there was a nearly linear decline in plasma tricarballylate.4. Tricarballylate was a competitive inhibitor of the enzyme, aconitate hydratase (aconitase; EC 4.2.1 .3), and the inhibitor constant, K I , was 0.52 mM. This KI value was similar to the Michaelis-Menten constant (K,) of the enzyme for citrate.5. When liver slices from sheep were incubated with increasing concentrations of tricarballylate, [I4C]acetate oxidation decreased. However, even at relatively high concentrations (8 mM), oxidation was still greater than 80% of the maximum. Oxidation of [I4C]acetate by isolated rat liver cells was inhibited to a greater extent by tricarballylate. Concentrations as low as 0.5 mM caused a 30% inhibition of citric acid cycle activity.

The Tricarballylate Utilization ( tcuRABC ) Genes of Salmonella enterica Serovar Typhimurium LT2

“…It is not clear how tricarballylate causes grass tetany; however, it is known that tricarballylate is a good chelator of magnesium ions and that it enhances excretion of this important divalent metal ion (33). In addition, tricarballylate is known to be a potent inhibitor of aconitase, a key enzyme of the Krebs cycle (26,29,33). This effect on aconitase makes tricarballylate particularly toxic to organisms that rely on the Krebs cycle for energy generation and are unable to catabolize tricarballylate into nontoxic metabolites.…”

Synthesis, chemical speciation and SOD mimic assays of tricarballylic acid–copper(II) and imidazole–tricarballylic acid–copper(II) complexes

“…It is present in several natural products as Fumonisin B1, B2, AAL Toxin TA and it is a fragment of the inhibitor of farnesyl-protein transferase (FPTase) [4,5]. In the living organisms, H 3 TCA is related to malfunctions [6] and due to its participation in the zinc excretion through the interaction and chelation with this metal ion [7] it is suggested that it is partly responsible for the deficiency of Zn. On the other hand, in recent years, polycarboxylic acids (bi and tricarboxylic) have attracted the attention of many researchers because of their participation as building blocks in metal-organic frameworks [8,9].…”

Facile Synthesis of (R,R) and of (R,S) Tricarballylic Acid Anhydride and Imide Derivatives

“…[4] It has been established that TCA 5 is produced by rumen bacteria and that it influences ruminant tissue metabolism. [5,6] Previously [7] we have described the synthesis of the 4-(5-nonyloxycarbonyl)-3-substituted butanoic acids and methyl esters like those found in Fumonisin B 1 (1a), B 2 (2b), AAL Toxin T A (3) and Actinoplanic acid 4 ( Figure 1) as a part of sphingosine analogs.…”