From amino acid mixtures to peptides in liquid sulphur dioxide on early Earth

The formation of peptide bonds is one of the most important biochemical reaction steps. Without the development of structurally and catalytically active polymers, there would be no life on our planet. However, the formation of large, complex oligomer systems is prevented by the high thermodynamic barrier of peptide condensation in aqueous solution. Liquid sulphur dioxide proves to be a superior alternative for copper-catalyzed peptide condensations. Compared to water, amino acids are activated in sulphur dioxide, leading to the incorporation of all 20 proteinogenic amino acids into proteins. Strikingly, even extremely low initial reactant concentrations of only 50 mM are sufficient for extensive peptide formation, yielding up to 2.9% of dialanine in 7 days. The reactions carried out at room temperature and the successful use of the Hadean mineral covellite (CuS) as a catalyst, suggest a volcanic environment for the formation of the peptide world on early Earth.

Use of low dosage amino acid blends to prevent stress-related piglet diarrhea

Weaning is a challenging period for piglets associated with reduced feed intake, impairment of gut integrity, and diarrhea. Previous studies demonstrate that supplementation with single functional amino acids promote piglets’ performance due to the improvement of intestinal health. Thus, we hypothesized that a combination of functional amino acids provided beyond the postulated requirement for growth could facilitate the weaning transition. Ninety piglets, initially stressed after weaning by 100 min overland transport, received a control diet or the same diet supplemented with a low-dosed (0.3 %) mixture of amino acids (AAB-1: L-arginine, L-leucine, L-valine, L-isoleucine, L-cystine; AAB-2: L-arginine, L-leucine, L-valine, L-isoleucine, L-cystine, L-tryptophan) for 28 days. Fecal consistency was ranked daily, growth performance was assessed weekly. On day 1 and 14 of the trial, blood samples were collected from a subset of 10 piglets per group to assess concentrations of insulin-like growth factor 1. After 28 days of feeding, tissues were obtained from the same piglets to analyze gut morphology and relative mRNA expression of genes related to gut function. Even if the stress response as indicated by rectal temperature was not different between the groups, pigs supplemented with AAB-2 showed firmer feces after weaning and less days with diarrhea compared to control. Furthermore, the jejunal expression of the MUC-2 gene was reduced (P < 0.05) in group AAB-2. Both amino acid mixtures increased crypt depth in the duodenum. Collectively, the given results indicate that 0.3 % extra amino acid supplementation might alleviate post-weaning diarrhea but did not alter growth performance of weanling piglets.

Peptide formation as on the early Earth: from amino acid mixtures to peptides in sulphur dioxide

The formation of peptide bonds is one of the most important biochemical reaction steps. Without the development of structurally and catalytically active polymers, there would be no life on our planet. Intensive research is being conducted on possible reaction pathways for the formation of complex peptides on the early Earth. Salt-induced peptide formation (SIPF) by metal catalysis is one possible pathway for abiotic peptide synthesis. The high salt concentration supports dehydration in this process. However, the formation of large, complex oligomer systems is prevented by the high thermodynamic barrier of peptide condensation in aqueous solution. Liquid sulphur dioxide proves to be a superior alternative for copper-catalysed peptide condensation. Compared to water, the amino acids are activated in sulphur dioxide, which leads to the incorporation of all 20 proteinogenic amino acids into the resulting proteins and thus to a large variety of products. Strikingly, even extremely low initial reactant concentrations of only 50 mM are sufficient for extensive peptide formation, leading to an overall yield of 2.9% for dialanine in 7 days. The reactions carried out at room temperature and the successful use of the Hadean mineral covellite as a catalyst, suggest a volcanic environment for the formation of the peptide world on early Earth as a likely scenario.

DEVELOPMENT OF THE COMPONENT COMPOSITION OF AMINO ACID MIXTURES FOR THE NUTRITION OF PATIENTS WITH PHENYLKETONURIA

According to the Ministry of Health in the Republic of Belarus in 2019, there were about 500 patients with phenylketonuria (PKU). Phenylketonuria is a hereditary disease associated with a violation of the metabolism of amino acids, in particular phenylalanine (FA). This disease is accompanied by the accumulation of phenylalanine and its toxic products in the tissues, which leads to severe damage to the central nervous system, manifested in the form of impaired mental development. Many years of world experience shows that for the treatment of such patients, a special diet is prescribed using amino acid mixtures that do not contain phenylalanine or contain it in small amounts, as well as low-protein products based on starch, which are necessary to ensure an adequate energy value of the diet. The article presents the stages of development of the component composition of domestic amino acid mixtures for the nutrition of patients with phenylketonuria, taking into account their age characteristics.

Alanine, arginine, cysteine, and proline, but not glutamine, are substrates for, and acute mediators of, the liver-α-cell axis in female mice

The aim of this study was to identify the amino acids that stimulate glucagon secretion in mice and whose metabolism depends on glucagon receptor signaling. Pancreata of female C57BL/6JRj mice were perfused with 19 individual amino acids and pyruvate (at 10 mM), and secretion of glucagon was assessed using a specific glucagon radioimmunoassay. Separately, a glucagon receptor antagonist (GRA; 25–2648, 100 mg/kg) or vehicle was administered to female C57BL/6JRj mice 3 h before an intraperitoneal injection of four different isomolar amino acid mixtures (in total 7 µmol/g body wt) as follows: mixture 1 contained alanine, arginine, cysteine, and proline; mixture 2 contained aspartate, glutamate, histidine, and lysine; mixture 3 contained citrulline, methionine, serine, and threonine; and mixture 4 contained glutamine, leucine, isoleucine, and valine. Blood glucose, plasma glucagon, amino acid, and insulin concentrations were measured using well-characterized methodologies. Alanine ( P = 0.03), arginine ( P < 0.0001), cysteine ( P = 0.01), glycine ( P = 0.02), lysine ( P = 0.02), and proline ( P = 0.03), but not glutamine ( P = 0.9), stimulated glucagon secretion from the perfused mouse pancreas. However, when the four isomolar amino acid mixtures were administered in vivo, the four mixtures elicited similar glucagon responses ( P > 0.5). Plasma concentrations of total amino acids in vivo were higher after administration of GRA when mixture 1 ( P = 0.004) or mixture 3 ( P = 0.04) were injected. Our data suggest that alanine, arginine, cysteine, and proline, but not glutamine, are involved in the acute regulation of the liver-α-cell axis in female mice, as they all increased glucagon secretion and their disappearance rate was altered by GRA.

Alanine, arginine, and proline but not glutamine are the feed-back regulators in the liver-alpha cell axis in mice

AimTo identify the amino acids that stimulate glucagon secretion in mice and whether the metabolism of these relies on glucagon receptor signaling.MethodsPancreata of female C57BL/6JRj mice were perfused with 19 individual amino acids (1 mM) and secretion of glucagon was assessed using a specific glucagon radioimmunoassay. Separately, a glucagon receptor antagonist (GRA; 25-2648, 100 mg/kg) or vehicle was administered to female C57BL/6JRj mice three hours prior to an intraperitoneal injection of four different isomolar (in total 7 µmol/g body weight) amino acid mixtures; mixture 1: alanine, arginine, cysteine, and proline; mixture 2: asparatate, glutamate, histidine, and lysine; mixture 3: citrulline, methionine, serine, and threonine; and mixture 4: glutamine, leucine, isoleucine, and valine. Blood glucose, plasma glucagon, amino acid, and insulin concentrations were measured using well characterized methodologies.ResultsAlanine (P=0.03), arginine (P<0.001), and proline (P=0.03) but not glutamine (P=0.2) stimulated glucagon secretion from the perfused mouse pancreas. Cysteine had the numerically largest effect on glucagon secretion but did not reach statistical significance (P=0.08). However, when the four isomolar amino acid mixtures were administered there were no significant difference (P>0.5) in plasma concentrations of glucagon across mixture 1-4. Plasma concentrations of total amino acids were higher after administration of GRA when mixture 1 (P=0.004) or mixture 3 (P=0.04) were injected.ConclusionOur data suggest that alanine, arginine, and proline but not glutamine are involved in the liver-alpha cell axis in mice as they all increased glucagon secretion and their disappearance rate was altered by GRA.Graphical abstract