Names | |
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IUPAC name (2R)-4-amino-4-oxo-2-[ [(3S,4R,5R)-2,3,4,5-tetrahydroxyoxan-2-yl]methylamino]butanoic acid | |
Identifiers | |
3D model (JSmol) | |
PubChem CID | |
CompTox Dashboard (EPA) | |
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Properties | |
C10H18N2O8 [1] | |
Molar mass | 294.25852 [1] |
Appearance | off white crystals [1] |
Melting point | 118 °C (244 °F; 391 K) |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). |
Fructose-asparagine (F-Asn) is a glycosylamine compound that is most notably used by Salmonella during Salmonella-mediated inflammation of the intestine. In addition to Salmonella, several other species of bacteria may utilize fructose-asparagine as a nutrient. [2] The name of the genetic locus that encodes the uptake capability in Salmonella is fra. [3] This fra locus has five genes: fraR (a regulator), fraB a fructose-asparagine deglycase, fraD a sugar kinase, fraA a fructose-asparagine transporter, and fraE a L-asparaginase. [3] Notably, mutations in fraB cause the buildup of the toxic intermediate 6-phosphofuctose-aspartate (6-P-F-Asp). The buildup of 6-P-F-Asp has a bacteriostatic effect on fraB mutant cells, making FraB a potential drug target. [4]
Fructose-asparagine is a aminodeoxysugar. It takes the form of a pale yellow solid. It decomposes above 120 °C. [1]
Fructose-asparagine is formed when cooking food by way of the Maillard reaction. Fructose-asparagine can be prepared by refluxing D-glucose with sodium bisulfite in methanol, and then adding L-asparagine, and then acetic acid [1] or malonic acid. [3] An ion exchange resin then can separate the product from other contaminants. [1]
Fructose-asparagine is found naturally in some foods, with dried asparagus containing 1.4% and carrot containing 0.1%. [3]
A regulator gene that lies upstream of the fraBDAE operon. It is predicted to encode a transcription regulator that belongs to the GntR family. [3]
fraE encodes the periplasmic fructose-asparaginase FraE that removes ammonia from F-Asn to form fructose-aspartate (F-Asp). [5] Mutations in fraE do not prevent F-Asn utilization due to redundancy conferred by the ansB gene that codes for the asparaginase AnsB. [5] It is hypothesized fraE may have resulted from a past duplication of ansB, which then underwent selection for specificity for F-Asn. FraE is specific for F-Asn and cannot function as a general periplasmic asparaginase like ansB. [5]
fraA encodes a transporter of the Dcu family, which moves F-Asp, but not F-Asn, into the cytoplasm. [5]
fraD encodes the sugar kinase FraD that phosphorylates F-Asp into 6-phosphofuctose-aspartate (6-P-F-Asp). [6] It is unusual in that it can phosphorylate both the L and D stereoisomers of F-Asp. [6]
fraB functions as a deglycase that cleaves 6-P-F-Asp into glucose-6-phosphate (G-6-P) and aspartate. [4] Mutants lacking fraD or fraA are unable to grow in media containing only F-Asn, but are able to grow in media containing F-Asn along with glucose as an alternative carbon source. [4] However, fraB mutants are unable to grow on glucose in the presence of F-Asn. [4] This is due to the accumulation of 6-P-F-Asp inside the cell. This intermediate product has been shown to be bacteriostatic to Salmonella. [4] This property makes FraB a potential target for drug treatments selective to Salmonella. [4]
Many gastrointestinal Salmonella serovars encode the fra locus, presumably to utilize fructose-asparagine within the inflamed gut environment. When Salmonella infects a host, it uses two Type 3 secretion systems, encoded within the genes SPI1 and SPI2, to initiate inflammation. This disrupts normal microbiota, and creates alternative electron acceptors such as nitrate and tetrathionate, and even allows oxygen to accumulate near epithelial surfaces. [7] [8] [9] [10] Microbiota that would normally consume F-Asn are eliminated by inflammation, allowing Salmonella access to this nutrient. [11] The fra operon confers a fitness advantage to Salmonella in an inflamed intestinal tract. [3] However, this is not due to fructose-asparagine being an essential nutrient, but rather because fructose-asparagine is toxic to a fraB mutant of Salmonella, [4] Notable serovars of Salmonella enterica that do not utilize fructose-asparagine and are missing the fra operon include Typhi and Paratyphi A. [2] This is likely due to their extraintestinal niche within the host.
F-Asn is abundant in the intestinal tract of germ-free mice, but is difficult to detect in conventional mice. This suggests that there are members of the microbiota that can consume F-Asn. [11] [3] It was recently discovered that several Clostridium, Citrobacter, and Klebsiella species can utilize F-Asn. [2] Notably, C. difficile cannot utilize F-Asn. [2] Salmonella is able to eliminate competition from these species by causing inflammation within the host intestinal tract. This kills other members of the microbiota that consume F-Asn and leave Salmonella the sole user of the nutrient. [11] Bioinformatic approaches suggest that Salmonella may have acquired the fra genes by horizontal transfer from the Clostridia. [2]
Aspartic acid (symbol Asp or D; the ionic form is known as aspartate), is an α-amino acid that is used in the biosynthesis of proteins. Like all other amino acids, it contains an amino group and a carboxylic acid. Its α-amino group is in the protonated –NH+
3 form under physiological conditions, while its α-carboxylic acid group is deprotonated −COO− under physiological conditions. Aspartic acid has an acidic side chain (CH2COOH) which reacts with other amino acids, enzymes and proteins in the body. Under physiological conditions (pH 7.4) in proteins the side chain usually occurs as the negatively charged aspartate form, −COO−. It is a non-essential amino acid in humans, meaning the body can synthesize it as needed. It is encoded by the codons GAU and GAC.
Asparagine is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group, an α-carboxylic acid group, and a side chain carboxamide, classifying it as a polar, aliphatic amino acid. It is non-essential in humans, meaning the body can synthesize it. It is encoded by the codons AAU and AAC.
Salmonella enterica is a rod-shaped, flagellate, facultative anaerobic, Gram-negative bacterium and a species of the genus Salmonella. A number of its serovars are serious human pathogens; many of them are serovars of Salmonella enterica subsp. enterica.
Aspartate transaminase (AST) or aspartate aminotransferase, also known as AspAT/ASAT/AAT or (serum) glutamic oxaloacetic transaminase, is a pyridoxal phosphate (PLP)-dependent transaminase enzyme that was first described by Arthur Karmen and colleagues in 1954. AST catalyzes the reversible transfer of an α-amino group between aspartate and glutamate and, as such, is an important enzyme in amino acid metabolism. AST is found in the liver, heart, skeletal muscle, kidneys, brain, red blood cells and gall bladder. Serum AST level, serum ALT level, and their ratio are commonly measured clinically as biomarkers for liver health. The tests are part of blood panels.
Gut microbiota, gut microbiome, or gut flora, are the microorganisms, including bacteria, archaea, fungi, and viruses, that live in the digestive tracts of animals. The gastrointestinal metagenome is the aggregate of all the genomes of the gut microbiota. The gut is the main location of the human microbiome. The gut microbiota has broad impacts, including effects on colonization, resistance to pathogens, maintaining the intestinal epithelium, metabolizing dietary and pharmaceutical compounds, controlling immune function, and even behavior through the gut–brain axis.
Bacteroides fragilis is an anaerobic, Gram-negative, pleomorphic to rod-shaped bacterium. It is part of the normal microbiota of the human colon and is generally commensal, but can cause infection if displaced into the bloodstream or surrounding tissue following surgery, disease, or trauma.
Neutrophil elastase is a serine proteinase in the same family as chymotrypsin and has broad substrate specificity. Neutrophil elastase is secreted by neutrophils during inflammation, and destroys bacteria and host tissue. It also localizes to neutrophil extracellular traps (NETs), via its high affinity for DNA, an unusual property for serine proteases.
Amino acid synthesis is the set of biochemical processes by which the amino acids are produced. The substrates for these processes are various compounds in the organism's diet or growth media. Not all organisms are able to synthesize all amino acids. For example, humans can synthesize 11 of the 20 standard amino acids. These 11 are called the non-essential amino acids).
Aldolase B also known as fructose-bisphosphate aldolase B or liver-type aldolase is one of three isoenzymes of the class I fructose 1,6-bisphosphate aldolase enzyme, and plays a key role in both glycolysis and gluconeogenesis. The generic fructose 1,6-bisphosphate aldolase enzyme catalyzes the reversible cleavage of fructose 1,6-bisphosphate (FBP) into glyceraldehyde 3-phosphate and dihydroxyacetone phosphate (DHAP) as well as the reversible cleavage of fructose 1-phosphate (F1P) into glyceraldehyde and dihydroxyacetone phosphate. In mammals, aldolase B is preferentially expressed in the liver, while aldolase A is expressed in muscle and erythrocytes and aldolase C is expressed in the brain. Slight differences in isozyme structure result in different activities for the two substrate molecules: FBP and fructose 1-phosphate. Aldolase B exhibits no preference and thus catalyzes both reactions, while aldolases A and C prefer FBP.
Asparagine synthetase is a chiefly cytoplasmic enzyme that generates asparagine from aspartate. This amidation reaction is similar to that promoted by glutamine synthetase. The enzyme is ubiquitous in its distribution in mammalian organs, but basal expression is relatively low in tissues other than the exocrine pancreas.
GLUT5 is a fructose transporter expressed on the apical border of enterocytes in the small intestine. GLUT5 allows for fructose to be transported from the intestinal lumen into the enterocyte by facilitated diffusion due to fructose's high concentration in the intestinal lumen. GLUT5 is also expressed in skeletal muscle, testis, kidney, fat tissue (adipocytes), and brain.
In enzymology, an asparaginyl-tRNA synthase (glutamine-hydrolysing) is an enzyme that catalyzes the chemical reaction
Salmonella enterica subsp. enterica is a subspecies of Salmonella enterica, the rod-shaped, flagellated, aerobic, Gram-negative bacterium. Many of the pathogenic serovars of the S. enterica species are in this subspecies, including that responsible for typhoid.
In molecular biology, the amino acid kinase domain is a protein domain. It is found in protein kinases with various specificities, including the aspartate, glutamate and uridylate kinase families. In prokaryotes and plants the synthesis of the essential amino acids lysine and threonine is predominantly regulated by feed-back inhibition of aspartate kinase (AK) and dihydrodipicolinate synthase (DHPS). In Escherichia coli, thrA, metLM, and lysC encode aspartokinase isozymes that show feedback inhibition by threonine, methionine, and lysine, respectively. The lysine-sensitive isoenzyme of aspartate kinase from spinach leaves has a subunit composition of 4 large and 4 small subunits.
Colonization resistance is the mechanism whereby the intestinal microbiota protects itself against incursion by new and often harmful microorganisms.
PepB aminopeptidase is an enzyme which catalyses the following chemical reaction:
Peptidyl-Asp metalloendopeptidase is an enzyme. This enzyme catalyses the following chemical reaction
The Asx turn is a structural feature in proteins and polypeptides. It consists of three amino acid residues in which residue i is an aspartate (Asp) or asparagine (Asn) that forms a hydrogen bond from its sidechain CO group to the mainchain NH group of residue i+2. About 14% of Asx residues present in proteins belong to Asx turns.
The C4-dicarboxylate uptake family or Dcu family is a family of transmembrane ion transporters found in bacteria. Their function is to exchange dicarboxylates such as aspartate, malate, fumarate and succinate.
Cinnamycin is a tetracyclic antibacterial peptide produced by Streptomyces cinnamoneus containing 19 amino acid residues including the unusual amino acids threo-3-methyl-lanthionine, meso-lanthionine, lysinoalanine, and 3-hydroxyaspartic acid.