Unusual Amino Acids and Amines

KEY Fermenters: Oxidation or fermentation by gut bacteria producing acid; Use: Utilisation or assimilation by gut bacteria; Common: Combined use and O/F for widespread, moderate and minor gut colonisers (total bacteria: 500);

Unusual amino acids	Common	Species examples	All consumers	Prevalence in food	Human digestion, metabolism, interactions	Structure
D-Alanine	12	Citrobacter farmeri; Citrobacter freundii; Citrobacter koseri; Cronobacter sakazakii; Enterobacter asburiae; Enterobacter cancerogenus; Enterobacter cloacae;	125	D-Ala is > L-Ala in yogurt and yakult, and is also present in milk, kefir, sour milk; a wide variety of vegetables, beer, fish, treated corn and soy proteins, and fermented black beans (Marcone2020).	A non-essential AA. After peptidase hydrolysis, it is absorbed through brush border cells of the small intestine, via symport transporters (sodium-dependent SNAT2, sodium- and proton-dependent SNAT3, and sodium-dependent B⁰AT1).
β-Alanine	0		40	The peptide carnosine (from muscle) and vitamin B5 contain beta-Ala.	Upon being produced subsequent to protease hydrolysis, it is absorbed into brush border cells of the small intestine via sodium-dependent symport ATB⁰,⁺ and proton-dependent symport PAT1 transporters. Endogenously produced, also. Metabolised to malonate-semialdehyde and then to malonate.
δ-Aminovalerate	4	Citrobacter freundii; Enterobacter hormaechei subsp. hormaechei; Klebsiella quasipneumoniae subsp. quasipneumoniae; Raoultella ornithinolytica;	31	Found in ducks, chickens, pigs, and cow's milk.	A conditionally essential AA. After peptidase hydrolysis, it is absorbed through brush border cells of the small intestine, via sodium-dependent symport SNAT2 transporters, cystine-glutamate antiporter; alanine, serine, cysteine-preferring transporter 2 (ASCT2) and antiport 4F2hc/y⁺LAT2. It is also transported via antiports rBAT/b⁰,⁺AT and 4F2 hc/xCT (as cystine). Possibly synthesised from Lys, Arg and/or Pro by gut bacteria.
Betaine	1	Enterobacter hormaechei subsp. hormaechei;	49	From beetroot, broccoli, grains, shellfish and spinach.	A non-essential AA. After peptidase hydrolysis, it is absorbed through brush border cells of the small intestine, via sodium(sym)-, proton(sym)- and potassium(anti)-dependent symport EAAT3 and antiport 4F2 hc/xCT transporters. Precursor to S-adenosylmethionine; hepatoprotector.
L-Citrulline	0		13	Found in watermelon, squash, pumpkins and cucumber.	A conditionally essential AA. After peptidase hydrolysis, it is absorbed through brush border cells of the small intestine, via the sodium-dependent antiport ASCT2 transporter. Can also be transported with the neutral AA B⁰AT1 and ATB⁰,⁺ transporters. Serum concentrations increase in patients with chronic kidney disease (Toyohara2010). Not integrated into proteins. Participates in intrahepatic transformation of ammonia to urea, the de novo synthesis of arginine from glutamine in gut and kidney, the nitric oxide synthesis (Rabier1995).
Hippurate	2	Enterococcus faecalis; Streptococcus agalactiae;	22	Xenobiotic from gut metabolism of benzoic acid (Pallister2017). Phenolic compounds from wine, tea and fruit juices are converted to hippurate.	A conditionally essential AA. After peptidase hydrolysis, it is absorbed through brush border cells of the small intestine, via proton-dependent symport PAT1 & PAT2 transporters. Can also be transported with the neutral AA B⁰AT1 and ATB⁰,⁺ transporters. Serum concentrations increase in patients with chronic kidney disease (Toyohara2010). Reduced levels in the urine of autism spectrum disorder and non-typical neurodevelopment children (SoteloOrozco2023).
Histamine	1	Enterobacter hormaechei subsp. hormaechei;	12	From tuna, mackerel, anchovy, spinach, wine, cheese, sausage and fermented foods.	An essential AA. After peptidase hydrolysis, it is absorbed through brush border cells of the small intestine, via sodium-dependent symport SNAT2 transporters and the uniport CAT-1 transporters. Possibly transported with the neutral AA B⁰AT1 and ATB⁰,⁺ transporters. Absorbed through the gut or synthesised from histidine, and metabolised by histamine N-methyltransferase/monoamine oxidase B route or diamine oxidase route (Neumann2021).
DL-Kynurenine	0		12	Endogenously produced in the brain (neuroprotective) and other tissues from tryptophan.	Tryptophan metabolism to kynurenine is catalysed by tryptophan dioxygenase or indoleamine dioxygenase. Kynurenine can be transformed to kynurenic acid, quinolinic acid and picolinic acid. Serum concentrations increase in patients with chronic kidney disease (Toyohara2010).
Norleucine	0		12	Found in cow's milk.
Ornithine	2	Klebsiella pneumoniae; Serratia marcescens;	53	From meat, fish, dairy (including cheese), and eggs	Produced endogenously when arginine is metabolised with arginase to produce urea. An important component of the urea cycle.
Sarcosine	0		20	From egg yolks, legumes, nuts, certain vegetables, turkey, ham, and other meats.	Reversibly transformed to glycine (sarcosine dehydrogenase/glycine-N-methyl transferase).
Trigonelline	1	Enterobacter hormaechei subsp. hormaechei;	13	Found in coffee, barley, rock melon, corn, onions, peas, soybeans, and tomatoes.	Breakdown product of vitamin B3 (niacin).
Tryptamine	1	Enterobacter hormaechei subsp. hormaechei;	9	Plants (particularly legumes), fungi and animals.	tryptophan decarboxylase removes the carboxylic acid group on the α-carbon of tryptophan. Monoamine oxidases A and B are the primary enzymes involved in tryptamine metabolism to produce indole-3-acetaldehyde
Pyroglutamate	0		11	Formed by intramolecular lactamisation of glutamate residues at the N-terminus of a peptide. This can occur when food is heated. PyroGlu-Leu dipeptide is observed in fermented foods.	SD rats fed wheat gluten hydrosylate showed increased blood levels of pyroglutamate.
Alaninamide	1	Intestinibacter bartlettii;	21	Artificially produced.
α-Aminobutyrate	0		13	A non-proteinogenic amino acid, also called homoalanine.	Involved in glutathione metabolism. Generated by transamination of 2-oxobutyrate. Serum concentrations decline in patients with chronic kidney disease (Toyohara2010).
3-Aminobutyrate	0		3	Found in cereal products, cow's milk and is widespread in plants, where it stimulates plant defenses against invasive pathogens. A non-proteinogenic amino acid.
γ-aminobutyrate	5	Cronobacter sakazakii; Enterobacter hormaechei subsp. hormaechei; Klebsiella pneumoniae; Klebsiella quasipneumoniae subsp. quasipneumoniae; Raoultella ornithinolytica;	84	Isolated from fermented foods, tea leaves, mulberry leaves, tomato, animals, lactic acid bacteria (LAB), yeasts and moulds (Sahab2020). A non-proteinogenic amino acid.	γ-aminobutyric acid (GABA) is synthesised by glutamic acid decarboxylase which catalyses the decarboxylation of L-glutamic acid. The principal inhibitory neurotransmitter and is produced endogenously. Absorbed into brush border cells of the small intestine via the proton-dependent symport PAT1 transporter. However, exogenous GABA is unlikely to pass the blood-brain barrier.
L-Norvaline	0		10	From meat, eggs, blackcurrants and buckwheat. A non-proteinogenic amino acid.	Non-essential amino acid. Inhibits arginase. A protein amino acid mimic that can cause cytotoxicity and mitochondrial disfunction at high concentrations; canonical amino acids, valine, isoleucine and leucine, are protective against norvaline toxicity in vitro (Samardzic2019).
L-Hydroxyproline	1	Serratia marcescens;	11	Comes from meat and bone meal, poultry meat, and salmon.	A significant component of human collagen. HO-Pro is formed endogenously when proline is oxidised in the presence of procollagen-proline dioxygenase. After peptidase hydrolysis, it is absorbed through brush border cells of the small intestine, via sodium-dependent IMINO transporters. Serum concentrations increase in patients with chronic kidney disease (Toyohara2010).
Casamino-acids	3	Bifidobacterium pseudolongum; Cloacibacillus evryensis; Terrisporobacter glycolicus;	35	A mixture of amino acids produced upon hydrolysis of casein (milk). The hydrolysis process destroys tryptophan and any vitamins and growth factors present.
D-Glucosaminate	0		4	A component of bacterial lipopolysaccharides. Degradation product of chitosan.
o-Aminobenzoate	0		7	From mexican groundcherries, caraway, cinnamon, apples, and guava. Anthanilic acid methyl ester is used extensively as a flavouring agent (grape) and in perfumery.	Anthranilic acid is biosynthesised from chorismic acid during the production of tryptophan; consequently, not endogenously produced by humans (except by gut bacteria). The acid is a breakdown product of tryptophan metabolism (Okuno2008).
m-Aminobenzoate	0		0
p-Aminobenzoate	1	Acidaminococcus fermentans;	5	brewer's yeast, organ meat, mushrooms, whole grains, and spinach	Also called PABA, this compound is used for the synthesis of folate in the gut - but not in the human body.
Putrescine	6	Cronobacter sakazakii; Enterobacter cancerogenus; Enterobacter cloacae; Klebsiella pneumoniae; Klebsiella quasipneumoniae subsp. quasipneumoniae; Raoultella ornithinolytica;	52	High levels in citrus fruits (1.5 umol/g), green peppers (0.8 umol/g), wheat germ (0.7 umol/g) and soybean sprouts (MunozEsparza2019).	Endogenously synthesised by ornithine decarboxylase-mediated decarboxylation of ornithine. Low acute toxicity.
Benzylamine	0		7	Elevated levels in corn and cabbage, with smaller amounts carrots, apples and lettuce.	Has been used as for motion sickness. Metabolised by monoamine oxidase B to benzaldehyde.
Butylamine	0		8	Found in kale, cocoa, cucumbers, some cheeses and milk products, brown bread, fish and other seafood.	A breakdown product of protein and amino acid metabolism. Accumulates in the gastric juices, along with numerous other aliphatic amines, of individuals with acute renal failure (Lichtenberger1993). Absorbed by gastric epithelial cells and can enter the blood stream. Probably eliminated through renal excretion or metabolised by CP450 to butyl hydroxylamine in the liver.