fumaric-acid and acrylic-acid

Nicotinic acid (niacin) has been used for decades as an antidyslipidemic drug in man. Its main target is the hydroxy-carboxylic acid receptor HCA2 (GPR109A), a G protein-coupled receptor. Other acids and esters such as methyl fumarate also interact with the receptor, which constituted the basis for the current study. We synthesized a novel series of substituted propenoic acids, such as fumaric acid esters, fumaric acid amides and cinnamic acid derivatives, and determined their affinities for the HCA2 receptor. We observed a rather restricted binding pocket on the receptor with trans-cinnamic acid being the largest planar ligand in our series with appreciable affinity for the receptor. Molecular modeling and analysis of the structure-activity relationships in the series suggest a planar trans-propenoic acid pharmacophore with a maximum length of 8 Å and out-of-plane orientation of the larger substituents.

Topics: Acrylates; Humans; Models, Molecular; Molecular Structure; Protein Binding; Receptors, G-Protein-Coupled; Receptors, Nicotinic; Structure-Activity Relationship

Fifteen potential precursors of propionate were tested for their ability to decrease CH4 production by ruminal fluid in vitro. Sodium acrylate and sodium fumarate produced the most consistent effects in batch cultures, with 50 % of the added precursors being fermented to propionate and CH4 production decreasing by between 8 and 17 %, respectively. Additives were more effective when added as free acids, but this also decreased the pH and may have inhibited fibre digestion. Changing the dietary substrate from predominantly grass hay to predominantly concentrate had no influence on the effectiveness of acrylate and fumarate. In an in vitro fermentor (the rumen simulating technique, Rusitec) with a grass hay-concentrate (50:50, w/w) diet as substrate, both compounds were again fermented to propionate (33 and 44 % conversion to propionate, respectively). However, fumarate appeared more effective as a H2 sink compound. It was calculated to capture 44 % of the H2 previously used for CH4 formation compared with a 22 % capture of H2 with acrylate. Fumarate also caused a stimulation in fibre digestion. Thus, sodium fumarate was the preferred propionate precursor for use as a feed ingredient to decrease CH4 emissions from ruminants.

Topics: Acids; Acrylates; Animals; Diet; Dietary Fiber; Digestion; Electrons; Fermentation; Food Additives; Fumarates; Hydrogen-Ion Concentration; Methane; Propionates; Rumen; Ruminants; Salts; Sheep