WordNet

a salt of phosphoric acid (同)orthophosphate, inorganic_phosphate
carbonated drink with fruit syrup and a little phosphoric acid
three people considered as a unit (同)threesome, triad, trinity
a set of three similar things considered as a unit (同)triad, triplet, triple
a musical composition for three performers
three performers or singers who perform together
any monosaccharide sugar containing three atoms of carbon per molecule
an enzyme that catalyzes its substrate to an isomeric form

PrepTutorEJDIC

〈U〉リン酸塩 / 《複数形で》リン酸肥料
三ツ組,3人組 / 三重唱[曲,団],三重奏[曲,団]

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/06/25 23:58:58」(JST)

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Triose-phosphate isomerase (TPI or TIM) is an enzyme (EC 5.3.1.1) that catalyzes the reversible interconversion of the triose phosphate isomers dihydroxyacetone phosphate and D-glyceraldehyde 3-phosphate.

Dihydroxyacetone phosphate	triose phosphate isomerase	D-glyceraldehyde 3-phosphate





	triose phosphate isomerase

Compound C00111 at KEGG Pathway Database.Enzyme 5.3.1.1 at KEGG Pathway Database.Compound C00118 at KEGG Pathway Database.

TPI plays an important role in glycolysis and is essential for efficient energy production. TPI has been found in nearly every organism searched for the enzyme, including animals such as mammals and insects as well as in fungi, plants, and bacteria. However, some bacteria that do not perform glycolysis, like ureaplasmas, lack TPI.

In humans, deficiencies in TPI are associated with a progressive, severe neurological disorder called triose phosphate isomerase deficiency. Triose phosphate isomerase deficiency is characterized by chronic hemolytic anemia. While there are various mutations that cause this disease, most include the mutation of glutamic acid at position 104 to aspartic acid.^[1]

Triose phosphate isomerase is a highly efficient enzyme, performing the reaction billions of times faster than it would occur naturally in solution. The reaction is so efficient that it is said to be catalytically perfect: It is limited only by the rate the substrate can diffuse into and out of the enzyme's active site.^[2]^[3]

Mechanism

The mechanism involves the intermediate formation of an "enediol". The relative free energy of each ground state and transition state has been determined experimentally, and is displayed in the figure.^[2]

The structure of TPI facilitates the conversion between dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (GAP). The nucleophilic glutamate 165 residue of TPI deprotonates the substrate,^[4] and the electrophilic histidine 95 residue donates a proton to form the enediol intermediate.^[5]^[6] When deprotonated, the enediolate then collapses and, abstracting a proton from protonated glutamate 165, forms the GAP product. Catalysis of the reverse reaction proceeds analogously, forming the same enediol but with enediolate collapse from the oxygen at C2.^[7]

TPI is diffusion-limited. In terms of thermodynamics, DHAP formation is favored 20:1 over GAP production.^[8] However, in glycolysis, the use of GAP in the subsequent steps of metabolism drives the reaction toward its production. TPI is inhibited by sulfate, phosphate, and arsenate ions, which bind to the active site.^[9] Other inhibitors include 2-phosphoglycolate, a transition state analog, and D-glycerol-1-phosphate, a substrate analog.^[10]

Side view of triose phosphate isomerase dimer.

Structure

Triose phosphate isomerase is a dimer of identical subunits, each of which is made up of about 250 amino acid residues. The three-dimensional structure of a subunit contains eight α-helices on the outside and eight parallel β-strands on the inside. In the illustration, the ribbon backbone of each subunit is colored in blue to red from N-terminus to C-terminus. This structural motif is called an αβ-barrel, or a TIM-barrel, and is by far the most commonly observed protein fold. The active site of this enzyme is in the center of the barrel. A glutamic acid residue and a histidine are involved in the catalytic mechanism. The sequence around the active site residues is conserved in all known triose phosphate isomerases.

The structure of triose phosphate isomerase contributes to its function. Besides the precisely placed glutamate and histidine residues to form the enediol, a ten- or eleven-amino acid chain of TPI acts as a loop to stabilize the intermediate. The loop, formed by residues 166 to 176, closes and forms a hydrogen bond to the phosphate group of the substrate. This action stabilizes the enediol intermediate and the other transition states on the reaction pathway.^[7]

In addition to making the reaction kinetically feasible, the TPI loop sequesters the reactive enediol intermediate to prevent decomposition to methylglyoxal and inorganic phosphate. The hydrogen bond between the enzyme and the phosphate group of the substrate makes such decomposition stereoelectronically unfavorable.^[7] Methylglyoxal is a toxin and, if formed, is removed through the glyoxalase system.^[11] The loss of a high-energy phosphate bond and the substrate for the rest of glycolysis makes formation of methylglyoxal inefficient.

Studies suggest that a lysine close to the active site (at position 12) is also crucial for enzyme function. The lysine, protonated at physiological pH, may help neutralize the negative charge of the phosphate group. When this lysine is mutated to a neutral amino acid, TPI loses all function, but mutants with a different positively charged amino acid retain some function.^[12]

References

^ Orosz, F.; Oláh, J. (2008). "Triosephosphate isomerase deficiency: facts and doubts". IUBMB Life 58 (12): 703–715. doi:10.1080/15216540601115960. PMID 17424909.
^ ^a ^b Albery, W. J.; Knowles, J. R. (1976). "Free-Energy Profile for the Reaction Catalyzed by Triosephosphate Isomerase". Biochemistry 15 (25): 5627–5631. doi:10.1021/bi00670a031. PMID 999838.
^ Rose, I.A.; Fung first2 = W.J.; Warms first3 = J.V.B. (1990). "Proton diffusion in the active site of triosephosphate isomerase". Biochemistry 29 (18): 4312–4317. doi:10.1021/bi00470a008. PMID 2161683.
^ Alber, T.; Banner, D.W.; Wilson, I.A. (1981). "On the three-dimensional structure and catalytic mechanism of triose phosphate isomerase.". Phil. Trans. R. Soc. 293 (1063): 159–171. doi:10.1098/rstb.1981.0069. PMID 6115415.
^ Nickbarg, E.B.; Davenport, R.C.; Knowles, J.R. (1988). "Triose Phosphate Isomerase: Removal of a Putatively Electrophilic Histidine Residue Results in a Subtle Change in Catalytic Mechanism.". Biochemistry 27 (16): 5948–5960. doi:10.1021/bi00416a019. PMID 2847777.
^ Komives, E.A.; Chang, L.C.; Knowles, J.R. (1991). "Electrophilic Catalysis in Triosephosphate Isomerase: the Role of Histidine-95.". Biochemistry 30 (12): 3011–3019. doi:10.1021/bi00226a005. PMID 2007138.
^ ^a ^b ^c Knowles, J.R. (1991). "Enzyme catalysis: not different, just better". Nature 350 (6314): 121–124. doi:10.1038/350121a0. PMID 2005961.
^ Harris, T.K.; Cole, R.N.; Mildvan, A.S. (1998). "Proton Transfer in the Mechanism of Triosephosphate Isomerase.". Biochemistry 37 (47): 16828–16838. doi:10.1021/bi982089f. PMID 9843453.
^ Lambeir, A.-M.; Opperdoes, F.R.; Wierenga, R.K. (1987). "Kinetic properties of triose-phosphate isomerase from Trypanosama brucei brucei". European Journal of Biochemistry 168 (1): 69–74. doi:10.1111/j.1432-1033.1987.tb13388.x. PMID 3311744.
^ Lolis, E.; Petsko, G.A. (1990). "Crystallographic Analysis of the Complex between Triosephosphate Isomerase and 2-Phosphoglycolate at 2.5-Å Resolution: Implications for Catalysis". Biochemistry 29 (28): 6619–6625. doi:10.1021/bi00480a010. PMID 2204418.
^ Creighton, D.J.; Hamilton, D.S. (2001). "Brief History of Glyoxalase I and What We Have Learned about Metal Ion-Dependent, Enzyme-Catalyzed Isomerizations.". Archives of Biochemistry and Biophysics 387 (1): 1–10. doi:10.1006/abbi.2000.2253. PMID 11368170.
^ Lodi, P.J.; Chang, L.C.; Komives, E.A. (1990). "Triosephosphate Isomerase Requires a Positively Charged Active Site: The Role of Lysine-12.". Biochemistry 33 (10): 2809–2814. doi:10.1021/bi00176a009. PMID 8130193.

UpToDate Contents

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1. 高リン血症の原因および治療 causes and treatment of hyperphosphatemia
2. 慢性腎疾患における高リン血症の治療 treatment of hyperphosphatemia in chronic kidney disease
3. 低リン血症の診断および治療 diagnosis and treatment of hypophosphatemia
4. 急性リン酸腎症 acute phosphate nephropathy
5. Chapter 6F：カルシウム・リンバランスにおけるホルモン調節 chapter 6f hormonal regulation of calcium and phosphate balance

English Journal

Dominance of Giardia duodenalis assemblage A and Enterocytozoon bieneusi genotype BEB6 in sheep in Inner Mongolia, China.

Ye J1, Xiao L2, Wang Y1, Guo Y3, Roellig DM2, Feng Y4.
Veterinary parasitology.Vet Parasitol.2015 Jun 15;210(3-4):235-9. doi: 10.1016/j.vetpar.2015.04.011. Epub 2015 Apr 24.
To examine the occurrence and genotype distribution of Giardia duodenalis and Enterocytozoon bieneusi in sheep, fecal specimens were collected from 162 lambs and 213 ewes on seven farms in the Hulunbeier Prairie in Inner Mongolia, China. By PCR analysis of the triose-phosphate isomerase gene, 16 of
PMID 25944405

Identification of polymorphic genes for use in assemblage B genotyping assays through comparative genomics of multiple assemblage B Giardia duodenalis isolates.

Wielinga C1, Thompson RC2, Monis P3, Ryan U4.
Molecular and biochemical parasitology.Mol Biochem Parasitol.2015 May 21;201(1):1-4. doi: 10.1016/j.molbiopara.2015.05.002. [Epub ahead of print]
Giardia duodenalis assemblage B is potentially a zoonotic parasite. The characterisation and investigation of isolates has been hampered by greater genetic diversity of assemblage B, limiting the application and utility of current genotyping loci. Since whole genome sequencing is the optimal high-th
PMID 26003141

'Super-perfect' enzymes: Structural stabilities and activities of recombinant triose phosphate isomerases from Pyrococcus furiosus and Thermococcus onnurineus produced in Escherichia coli.

Sharma P1, Guptasarma P2.
Biochemical and biophysical research communications.Biochem Biophys Res Commun.2015 May 8;460(3):753-8. doi: 10.1016/j.bbrc.2015.03.102. Epub 2015 Mar 27.
Triose phosphate isomerases (TIMs) are considered to be 'kinetically perfect' enzymes, limited in their activity only by the rates of diffusion of substrate and product molecules. Most studies conducted thus far have been on mesophile-derived TIMs. Here, we report studies of two extremophile-derived
PMID 25824038

Japanese Journal

EP-P39 Triose phosphate Isomerase enzyme is protected by Tau through its binding in a brain cell(Section VII Enzyme and Protein Engineering)

Park Seung-Ah,Kim Nam-Hee,Kim Yoon-Ha,Kwak Min-Jeong,Shin Jun-Seop,Park Hae-Won,Kim Chan-Wha
Journal of bioscience and bioengineering 108(S1), S111, 2009-11-00
NAID 110007520036

A role of RnlA in the RNase LS activity from Escherichia coli

Otsuka Yuichi,Koga Mitsunori,Iwamoto Akira [他],YONESAKI Tetsuro
Genes & genetic systems 82(4), 291-299, 2007-08-25
… Among these, triose phosphate isomerase exhibited a remarkable affinity to RnlA. …
NAID 10024394652

感染性胃腸炎患者から検出された消化管寄生性原虫の分子疫学的検討

烏谷竜哉,竹内潤子,泉山信司 [他]
愛媛県立衛生環境研究所年報 (8), 12-16, 2005-00-00
NAID 40015551886

「トリオースリン酸イソメラーゼ」

Triosephosphate isomerase
Identifiers
Symbol	TIM
Pfam	PF00121
Pfam clan	CL0036
InterPro	IPR000652
PROSITE	PDOC00155
SCOP	1tph
SUPERFAMILY	1tph
Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Search
PMC	articles
PubMed	articles
NCBI	proteins

triosephosphate isomerase
	Side view of triose P isomerase monomer, active site at top center
Identifiers
EC number	5.3.1.1
CAS number	9023-78-3
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 / EGO
Search
PMC	articles
PubMed	articles
NCBI	proteins

　　[★]

英: triose phosphate isomerase TPI
同: 三炭糖リン酸イソメラーゼ
関: (この酵素の構造)TIMバレル

「TPI deficiency」

　　[★]

同: triose phosphate isomerase

「triose-phosphate isomerase」

　　[★]

トリオースリン酸異性化酵素、トリオースリン酸イソメラーゼ

「phosphate」

　　[★]

n.

(化合物)リン酸塩、リン酸エステル、ホスフェート、フォスフェート、リン酸

関: inorganic phosphate、orthophosphate、orthophosphoric acid、phospho、phosphoester、phosphoric、phosphoric acid、phosphoric acid ester、phosphorus

「triose」

　　[★]

三炭糖、トリオース

[1] Orosz, F.; Oláh, J. (2008). "Triosephosphate isomerase deficiency: facts and doubts". IUBMB Life 58 (12): 703–715. doi:10.1080/15216540601115960. PMID 17424909.

[albery-2] Albery, W. J.; Knowles, J. R. (1976). "Free-Energy Profile for the Reaction Catalyzed by Triosephosphate Isomerase". Biochemistry 15 (25): 5627–5631. doi:10.1021/bi00670a031. PMID 999838.

[3] Rose, I.A.; Fung first2 = W.J.; Warms first3 = J.V.B. (1990). "Proton diffusion in the active site of triosephosphate isomerase". Biochemistry 29 (18): 4312–4317. doi:10.1021/bi00470a008. PMID 2161683.

[4] Alber, T.; Banner, D.W.; Wilson, I.A. (1981). "On the three-dimensional structure and catalytic mechanism of triose phosphate isomerase.". Phil. Trans. R. Soc. 293 (1063): 159–171. doi:10.1098/rstb.1981.0069. PMID 6115415.

[5] Nickbarg, E.B.; Davenport, R.C.; Knowles, J.R. (1988). "Triose Phosphate Isomerase: Removal of a Putatively Electrophilic Histidine Residue Results in a Subtle Change in Catalytic Mechanism.". Biochemistry 27 (16): 5948–5960. doi:10.1021/bi00416a019. PMID 2847777.

[6] Komives, E.A.; Chang, L.C.; Knowles, J.R. (1991). "Electrophilic Catalysis in Triosephosphate Isomerase: the Role of Histidine-95.". Biochemistry 30 (12): 3011–3019. doi:10.1021/bi00226a005. PMID 2007138.

[enzyme_catalysis-7] Knowles, J.R. (1991). "Enzyme catalysis: not different, just better". Nature 350 (6314): 121–124. doi:10.1038/350121a0. PMID 2005961.

[8] Harris, T.K.; Cole, R.N.; Mildvan, A.S. (1998). "Proton Transfer in the Mechanism of Triosephosphate Isomerase.". Biochemistry 37 (47): 16828–16838. doi:10.1021/bi982089f. PMID 9843453.

[9] Lambeir, A.-M.; Opperdoes, F.R.; Wierenga, R.K. (1987). "Kinetic properties of triose-phosphate isomerase from Trypanosama brucei brucei". European Journal of Biochemistry 168 (1): 69–74. doi:10.1111/j.1432-1033.1987.tb13388.x. PMID 3311744.

[10] Lolis, E.; Petsko, G.A. (1990). "Crystallographic Analysis of the Complex between Triosephosphate Isomerase and 2-Phosphoglycolate at 2.5-Å Resolution: Implications for Catalysis". Biochemistry 29 (28): 6619–6625. doi:10.1021/bi00480a010. PMID 2204418.

[11] Creighton, D.J.; Hamilton, D.S. (2001). "Brief History of Glyoxalase I and What We Have Learned about Metal Ion-Dependent, Enzyme-Catalyzed Isomerizations.". Archives of Biochemistry and Biophysics 387 (1): 1–10. doi:10.1006/abbi.2000.2253. PMID 11368170.

[12] Lodi, P.J.; Chang, L.C.; Komives, E.A. (1990). "Triosephosphate Isomerase Requires a Positively Charged Active Site: The Role of Lysine-12.". Biochemistry 33 (10): 2809–2814. doi:10.1021/bi00176a009. PMID 8130193.

リンク元	「トリオースリン酸イソメラーゼ」「TPI deficiency」
拡張検索	「triose-phosphate isomerase」
関連記事	「phosphate」「triose」

匿名

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案内

案内

triose phosphate isomerase