Thiamine pyridinylase | |||||||||
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Identifiers | |||||||||
EC no. | 2.5.1.2 | ||||||||
CAS no. | 9030-35-7 | ||||||||
Databases | |||||||||
IntEnz | IntEnz view | ||||||||
BRENDA | BRENDA entry | ||||||||
ExPASy | NiceZyme view | ||||||||
KEGG | KEGG entry | ||||||||
MetaCyc | metabolic pathway | ||||||||
PRIAM | profile | ||||||||
PDB structures | RCSB PDB PDBe PDBsum | ||||||||
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Aminopyrimidine aminohydrolase | |||||||||
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Identifiers | |||||||||
EC no. | 3.5.99.2 | ||||||||
Databases | |||||||||
IntEnz | IntEnz view | ||||||||
BRENDA | BRENDA entry | ||||||||
ExPASy | NiceZyme view | ||||||||
KEGG | KEGG entry | ||||||||
MetaCyc | metabolic pathway | ||||||||
PRIAM | profile | ||||||||
PDB structures | RCSB PDB PDBe PDBsum | ||||||||
Gene Ontology | AmiGO / QuickGO | ||||||||
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Thiaminase is an enzyme that metabolizes or breaks down thiamine into pyrimidine and thiazole. It is an antinutrient when consumed.
The old name was "aneurinase". [1]
There are two types with different Enzyme Commission numbers: [2]
Thiaminase I works to cleave the pyrimidine ring in thiamin from the thiazolium ring at the methylene bridge. From there it adds a base compound to the pyrimidine, creating an analogue inhibitor of thiamin. Thiaminase I has the ability to use a multitude of C-N cleaving nucleophilic substrates like cysteine, pyridine, aniline, veratrylamine, dithiothreitol, and quinoline. [7]
When analyzing the structure of Thiaminase I it shows a fold similar to that of group II periplasmic binding proteins like maltose-binding protein. [8] These periplasmic binding proteins have two domains that each contain an α/β fold. These two domains come together to form a deep cleft that are connected by three crossover segments. Due to this structure scientists proposed that Thiaminase I could have evolved from prehistoric periplasmic binding protein that had been responsible for up taking thiamin. [8] Between the two domains, in the cleft, sit the active site for Thiaminase I. Along the cleft there are four acidic residues and six tyrosine residues. In order for Thiamin to interact with Thiaminase I it is positioned in the active site between the pyrimidine and Asp272 by two hydrogen bonds. The Glu241 the goes on to activate the Cys113 to attack C6 of the pyrimidine. This forms a zwitterionic intermediate. [8] The Glu241 causes and protonation and nucleophilic attack that results in the split of the bond between the pyrimidine and the thiazole. When observing the crystalline structure, it has two α/β-type domains separated by a large cleft. At room temperature the two molecules have a noncrystallographic twofold axis that are bridged by a sulfate ion. [9]
Thiaminase II cleaves but does not add a base compound. Thiaminase II can only use water as the nucleophile. [10]
Thiaminase II has been found to be TenA. In order to cleave the C-N bond between the thiazole and pyrimidine Thiaminase only uses water as its nucleophile. When viewing Thiaminase II it is found to have a crystal structure that has 11 helices surrounding a deep acidic pocket. [8] For each monomer present in the quaternary structure it interacts with two other monomers. There are several residues like Tyr112, Phe208, Tyr47, and Tyr163 that have some sort of contribution to the π- stacking environment surrounding the HMP ligand. [8] The Glu205 side chain will form a hydrogen bond with the N1 nitrogen in the pyrimidine ring. Next the Tyr163 and the Asp44 side chain come together to form the hydrogen bonds with the N3 and N4'. [8] Finally the Cys135 catalytic residue is positioned near the C2 in the pyridine ring to complete the split of thiamin into its heterocycles. [8]
This enzyme can be found in a variety of different sources. It can be found in marine organisms, plants, and bacteria. Since thiamine (vitamin B1) is a very important substance required for metabolic pathways by almost all organisms, it can be very detrimental to introduce Thiaminase to a system. Frequently an organism gains this enzyme by ingesting another organism that carries it. In most cases, prey fish will contain one of the bacteria that produces this enzyme. When that prey fish is consumed raw without treatment the bacteria will transfer to the consumer. [11] The consumer eventually will fall ill, even die, from a thiamine deficiency. This has been seen in different lab studies. Through these studies the enzyme has been found in zebra fish as well as red cornet fish. [11] Cooking thiaminase-containing foods usually inactivates the enzyme. [11]
Sources of thiaminase I include:
Sources of thiaminase II include:
It is still unclear what thiaminase does for fish, bacterial cell or insects that contain it. In ferns, thiaminase I is thought to offer protection from insects [18]
Studies have shown that thiamine hydrolase (thiaminase II), which was originally thought to be involved solely in the degradation of thiamine, has actually been identified as having a role in thiamine degradation with the salvage of the pyrimidine moiety. Thiamin hydrolysis product N-formyl-4-amino-5-aminomethyl-2-methylpyrimidine is transported into the cell and deformylated by the amidohydrolase ylmB and hydrolyzed to 5-aminoimidazole ribotide. [19]
It was described in 1941 as the cause of highly mortal ataxic neuropathy in farmed foxes fed with raw carp. [20]
It is also known as the cause of cerebrocortical necrosis of cattle and polioencephalomalasia of sheep eating thiaminase containing plants. [21] [22]
It was once causing economical losses in raising fisheries, e.g. in yellowtail fed raw anchovy as a sole feed for a certain period, and also in sea bream and rainbow trout. The same problem is being studied in a natural food chain system. [23]
The larvae of a wild silk worm Anaphe venata are being consumed in a rain forest district of Nigeria as a supplemental protein nutrition, and the heat-resistant thiaminase in it is causing an acute seasonal cerebellar ataxia named African seasonal ataxia or Nigerian seasonal ataxia. [24]
In 1860–61, Burke and Wills were the first Europeans to cross Australia south to north; on their return they subsisted primarily on raw nardoo-fern. It is possible that this led to their death due to the extremely high levels of thiaminase contained in nardoo. The Aborigines prepared nardoo by soaking the sporocarps in water for at least a day to avoid the effects of thiamine deficiency that would result from ingesting the leaves raw. In the explorers' journals they noted many symptoms of thiamine deficiency, so it is thought that they did not soak the nardoo long enough. Eventually thiamine deficiency could have led to their demise. [2] It is noteworthy to mention that there are several other hypotheses regarding what may have killed Burke and Wills and it is widely disagreed upon by historians and scientists alike.[ citation needed ]
Thiamine, also known as thiamin and vitamin B1, is a vitamin, an essential micronutrient for humans and animals. It is found in food and commercially synthesized to be a dietary supplement or medication. Phosphorylated forms of thiamine are required for some metabolic reactions, including the breakdown of glucose and amino acids.
Thiamine pyrophosphate (TPP or ThPP), or thiamine diphosphate (ThDP), or cocarboxylase is a thiamine (vitamin B1) derivative which is produced by the enzyme thiamine diphosphokinase. Thiamine pyrophosphate is a cofactor that is present in all living systems, in which it catalyzes several biochemical reactions.
Transketolase is an enzyme that, in humans, is encoded by the TKT gene. It participates in both the pentose phosphate pathway in all organisms and the Calvin cycle of photosynthesis. Transketolase catalyzes two important reactions, which operate in opposite directions in these two pathways. In the first reaction of the non-oxidative pentose phosphate pathway, the cofactor thiamine diphosphate accepts a 2-carbon fragment from a 5-carbon ketose (D-xylulose-5-P), then transfers this fragment to a 5-carbon aldose (D-ribose-5-P) to form a 7-carbon ketose (sedoheptulose-7-P). The abstraction of two carbons from D-xylulose-5-P yields the 3-carbon aldose glyceraldehyde-3-P. In the Calvin cycle, transketolase catalyzes the reverse reaction, the conversion of sedoheptulose-7-P and glyceraldehyde-3-P to pentoses, the aldose D-ribose-5-P and the ketose D-xylulose-5-P.
Purine nucleoside phosphorylase, PNP, PNPase or inosine phosphorylase is an enzyme that in humans is encoded by the NP gene. It catalyzes the chemical reaction
Thiamine deficiency is a medical condition of low levels of thiamine (vitamin B1). A severe and chronic form is known as beriberi. The name beriberi was possibly borrowed in the 18th century from the Sinhalese phrase බැරි බැරි (bæri bæri, “I cannot, I cannot”), owing to the weakness caused by the condition. The two main types in adults are wet beriberi and dry beriberi. Wet beriberi affects the cardiovascular system, resulting in a fast heart rate, shortness of breath, and leg swelling. Dry beriberi affects the nervous system, resulting in numbness of the hands and feet, confusion, trouble moving the legs, and pain. A form with loss of appetite and constipation may also occur. Another type, acute beriberi, found mostly in babies, presents with loss of appetite, vomiting, lactic acidosis, changes in heart rate, and enlargement of the heart.
Phosphoribosyl pyrophosphate (PRPP) is a pentose phosphate. It is a biochemical intermediate in the formation of purine nucleotides via inosine-5-monophosphate, as well as in pyrimidine nucleotide formation. Hence it is a building block for DNA and RNA. The vitamins thiamine and cobalamin, and the amino acid tryptophan also contain fragments derived from PRPP. It is formed from ribose 5-phosphate (R5P) by the enzyme ribose-phosphate diphosphokinase:
Pyruvate dehydrogenase is an enzyme that catalyzes the reaction of pyruvate and a lipoamide to give the acetylated dihydrolipoamide and carbon dioxide. The conversion requires the coenzyme thiamine pyrophosphate.
Phosphoribosylamine (PRA) is a biochemical intermediate in the formation of purine nucleotides via inosine-5-monophosphate, and hence is a building block for DNA and RNA. The vitamins thiamine and cobalamin also contain fragments derived from PRA.
The TPP riboswitch, also known as the THI element and Thi-box riboswitch, is a highly conserved RNA secondary structure. It serves as a riboswitch that binds thiamine pyrophosphate (TPP) directly and modulates gene expression through a variety of mechanisms in archaea, bacteria and eukaryotes. TPP is the active form of thiamine (vitamin B1), an essential coenzyme synthesised by coupling of pyrimidine and thiazole moieties in bacteria. The THI element is an extension of a previously detected thiamin-regulatory element, the thi box, there is considerable variability in the predicted length and structures of the additional and facultative stem-loops represented in dark blue in the secondary structure diagram Analysis of operon structures has identified a large number of new candidate thiamin-regulated genes, mostly transporters, in various prokaryotic organisms. The x-ray crystal structure of the TPP riboswitch aptamer has been solved.
The enzyme oxalyl-CoA decarboxylase (OXC) (EC 4.1.1.8), primarily produced by the gastrointestinal bacterium Oxalobacter formigenes, catalyzes the chemical reaction
In enzymology, a thiamine-phosphate diphosphorylase is an enzyme that catalyzes the chemical reaction
5′-Phosphoribosyl-5-aminoimidazole is a biochemical intermediate in the formation of purine nucleotides via inosine-5-monophosphate, and hence is a building block for DNA and RNA. The vitamins thiamine and cobalamin also contain fragments derived from AIR. It is an intermediate in the adenine pathway and is synthesized from 5′-phosphoribosylformylglycinamidine by AIR synthetase.
Glycineamide ribonucleotide is a biochemical intermediate in the formation of purine nucleotides via inosine-5-monophosphate, and hence is a building block for DNA and RNA. The vitamins thiamine and cobalamin also contain fragments derived from GAR.
Sulfur carrier protein ThiS adenylyltransferase is an enzyme with systematic name ATP:(ThiS) adenylyltransferase. This enzyme catalyses the following chemical reaction
Thiazole synthase (EC 2.8.1.10, thiG (gene)) is an enzyme with systematic name 1-deoxy-D-xylulose 5-phosphate:thiol sulfurtransferase. This enzyme catalyses the following chemical reaction
Aminopyrimidine aminohydrolase (EC 3.5.99.2, thiaminase, thiaminase II, tenA (gene)) is an enzyme with systematic name 4-amino-5-aminomethyl-2-methylpyrimidine aminohydrolase. This enzyme catalyses the following chemical reaction
Phosphomethylpyrimidine synthase is an enzyme with systematic name 5-amino-1-(5-phospho-D-ribosyl)imidazole formate-lyase . This enzyme catalyses the following chemical reaction
Thiazole tautomerase is an enzyme with systematic name 2-(2-carboxy-4-methylthiazol-5-yl)ethyl phosphate isomerase. This enzyme catalyses the following chemical reaction
Anaphe venata is a moth of the family Notodontidae. It was described by Arthur Gardiner Butler in 1878. It lives in Angola, Cameroon, the Central African Republic, the Republic of the Congo, the Democratic Republic of the Congo, Equatorial Guinea, Ghana, Ivory Coast, Nigeria, Tanzania and Togo.
Within the field of biochemistry, 4-amino-5-hydroxymethyl-2-methylpyrimidine (HMP) also known as toxopyrimidine together with its mono phosphate (HMP-P) and pyrophosphate (HMP-PP) esters are biogenetic precursors to the important biochemical cofactor thiamine pyrophosphate (TPP), a derivative of thiamine (vitamin B1).
Thiaminase I enzymes present in the culture solutions of Bacillus thiaminolyticus [3-5] and Clostridium sporogenes [6-8] have been highly purified and detailed kinetic studies performed. But, despite the importance thiaminase I enzyme in stock poisoning by bracken fern [9], there is limited information available on the properties of this or other fern thiaminases.
The thiaminase in the buffer extract of Anaphe pupae was type I
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