Degradation and de novo formation of nine major glucose degradation products during storage of peritoneal dialysis fluids

β-Carbolines are naturally occurring bioactive alkaloids found in foods and in vivo. This research reports the identification, characterization, mechanism of formation, and occurrence of perlolyrine (1-(5-(hydroxymethyl)furan-2-yl)-9H-pyrido[3,4-b]indole), a β-carboline with a furan moiety. Perlolyrine did not arise from l-tryptophan and hydroxymethylfurfural but from the reaction of l-tryptophan with 3-deoxyglucosone, an intermediate of carbohydrate degradation. The mechanism of formation occurs through 3,4-dihydro-β-carboline-3-carboxylic acid intermediates (imines), followed by the oxidation of C1′-OH to ketoimine and oxidative decarboxylation at C-3, along with dehydration and cyclization to afford the β-carboline with a furan moiety. The formation of perlolyrine was favored in acidic conditions and temperatures in the range of 70–110 °C. Perlolyrine occurred in the reactions of tryptophan with carbohydrates. The formation rate from fructose was much higher than from glucose. Sucrose also gave perlolyrine under acidic conditions and heating. Perlolyrine was identified in many foods by HPLC-MS and analyzed by HPLC-fluorescence. It occurred in many processed foods such as tomato products including tomato puree, fried tomato, ketchups, tomato juices, and jams but also in soy sauce, beer, balsamic vinegar, fruit juices, dried fruits, fried onion, and honey. The concentrations ranged from an undetected amount to 3.5 μg/g with the highest average levels found in tomato concentrate (1.9 μg/g) and soy sauce (1.5 μg/mL). The results show that perlolyrine formed during the heating process of foods. It is concluded that perlolyrine is widely present in foods and it is daily ingested in the diet.

Section: Discussionmentioning

confidence: 99%

Identification, Formation, and Occurrence of Perlolyrine: A β-Carboline Alkaloid with a Furan Moiety in Foods

Herraiz,

Peña,

Salgado

2023

“…30 They react with free amino groups of amino acids and proteins affording irreversible advanced glycation end products (AGEs), which may have a role in diseases such as diabetes mellitus, Alzheimer's disease, and atherosclerosis. 25,26,31,51 Their reaction with lysine, arginine, or cysteine affords α-dicarbonyl adducts in the early and advanced glycation process. 25,34 In this regard, the results presented here evidence the formation of α-dicarbonyl-derived βcarbolines from a reaction with tryptophan.…”

Section: ■ Discussionmentioning

confidence: 99%

“…1,2-Dicarbonyl compounds (α-oxoaldehydes) have been also reported in biological samples such as blood and plasma. , These compounds are cytotoxic and might induce cellular damage . They react with free amino groups of amino acids and proteins affording irreversible advanced glycation end products (AGEs), which may have a role in diseases such as diabetes mellitus, Alzheimer’s disease, and atherosclerosis. ,,, Their reaction with lysine, arginine, or cysteine affords α-dicarbonyl adducts in the early and advanced glycation process. , In this regard, the results presented here evidence the formation of α-dicarbonyl-derived β-carbolines from a reaction with tryptophan. These compounds could be a new type of AGEs.…”

Section: Discussionmentioning

confidence: 99%

Formation, Characterization, and Occurrence of β-Carboline Alkaloids Derived from α-Dicarbonyl Compounds and l-Tryptophan

Herraiz

Negrón

Mateo

et al. 2022

β-Carbolines (βCs) are naturally occurring bioactive alkaloids, whereas α-dicarbonyl compounds are reactive substances generated in foods and in vivo. In this work, L-tryptophan reacted with α-dicarbonyl compounds affording new βcarbolines. Glyoxal afforded 1-hydroxymethyl-β-carboline (HME-βC) and its 3-carboxylic acid, and methylglyoxal afforded 1-(1hydroxyethyl)-β-carboline (HET-βC) and its 3-carboxylic acid. 2), and 1-(1,5-dihydroxypent-3-en-1-yl)-β-carboline (3). The formation of these βCs increased under acidic conditions and with increasing temperature. A mechanism is proposed explaining the conversion of a carbonyl into a hydroxy group based on tautomerism and cyclization to the dihydro-βC-3-COOH intermediates, which were isolated and gave the βCs. These α-dicarbonyl-derived βCs occurred in model reactions of L-tryptophan with fructose or glucose incubated under heating and can be considered as advanced glycation end products (AGEs). They were also present in foods and formed during heating processes. HET-βC appeared in processed foods, reaching up to 309 ng/g, with the highest amount found in dried tomato, fried onion, toasted bread, and Manuka honey. HME-βC was only detected in some foods with lower amounts than HET-βC. HET-βC appeared in foods as a racemic mixture of enantiomers suggesting the same mechanism of formation as the synthetized product. α-Dicarbonyl-derived βCs (HET-βC, HME-βC, and 1a/b-3) occur in foods and food processing and, therefore, they are ingested during diet.

“…Flazin produced from fructose and sucrose after hydrolysis occurred in higher yields than that produced from glucose. The flazin precursor is the α-dicarbonyl compound 3-deoxyglucosone that is produced from carbohydrates, particularly fructose. − 3-Deoxyglucosone is a predominant α-dicarbonyl compound in foods, it is also present in biological samples, including blood and plasma. , The α-dicarbonyl derivatives react with free amino acids and proteins to give irreversible advanced glycation end products (AGEs), which may be involved in human diseases. ,,− As shown here, 3-deoxyglucosone reacts with l -Trp, affording flazin, which could be a new AGE product similar to other βCs derived from carbohydrates . The formation of flazin is not favored under normal physiological conditions, but it is easily produced in food processing and cooking.…”

Section: Discussionmentioning

confidence: 89%

Formation, Identification, and Occurrence of the Furan-Containing β-Carboline Flazin Derived from l-Tryptophan and Carbohydrates

Herraiz,

Salgado

2024

β-Carbolines (βCs) are bioactive indole alkaloids found in foods and in vivo. This work describes the identification, formation, and occurrence in foods of the βC with a furan moiety flazin (1-[5-(hydroxymethyl)furan-2-yl]-9H-pyrido [3,4-b]indole-3-carboxylic acid). Flazin was formed by the reaction of L-tryptophan with 3-deoxyglucosone but not with 5-hydroxymethylfurfural. Its formation was favored in acidic conditions and heating (70−110 °C). The proposed mechanism of formation occurs through the formation of intermediates 3,4-dihydro-β-carboline-3-carboxylic acid (imines), followed by the oxidation to C�O in the carbohydrate chain and aromatization to βC ring with subsequent dehydration steps and cyclization to afford the furan moiety. Flazin is generated in the reactions of tryptophan with carbohydrates. Its formation from fructose was higher than from glucose, whereas sucrose gave flazin under acidic conditions and heating owing to hydrolysis. Flazin was identified in foods by HPLC-MS, and its content was determined by HPLC-fluorescence. It occurred in numerous processed foods, such as tomato products, including crushed tomato puree, fried tomato, ketchup, tomato juices, and jams, but also in soy sauce, beer, balsamic vinegar, fruit juices, dried fruits, fried onions, and honey. Their concentrations ranged from not detected to 22.3 μg/mL, with the highest mean levels found in tomato concentrate (13.9 μg/g) and soy sauce (9.4 μg/mL). Flazin was formed during the heating process, as shown in fresh tomato juice and crushed tomatoes. These results indicate that flazin is widely present in foods and is daily uptaken in the diet.