Disease relevance of TPI1

• Triosephosphate isomerase- and glyceraldehyde-3-phosphate dehydrogenase-reactive autoantibodies in the cerebrospinal fluid of patients with multiple sclerosis [1].
• To carry out biochemical and biophysical characterization, purified recombinant M. tuberculosis TPI produced in Escherichia coli was used [2].
• Biochemical and functional characterization of triosephosphate isomerase from Mycobacterium tuberculosis H37Rv [2].
• Keywords: human lung squamous carcinoma * tumor antigen * autoantibody * serological proteome analysis * Tim * MnSOD [3].
• Triose-phosphate isomerase (TPI; D-glyceraldehyde-3-phosphate ketol-isomerase, EC 5.3.1.1) deficiency is a recessive disorder that results in hemolytic anemia and neuromuscular dysfunction [4].

Psychiatry related information on TPI1

• Morphological changes are shown in the muscle biopsy specimens of an 8-year-old girl who suffered from a triosephosphate isomerase (TPI) deficiency, resulting in a chronic, nonspherocytic, hemolytic anemia, mental retardation and neuromuscular impairment [5].
• For other enzymes (aldolase, phosphoglucose isomerase, triosephosphate isomerase and lactate dehydrogenase) no changes in enzyme activities corresponding to those found in dementia are observed in the normal ageing process [6].

High impact information on TPI1

• Separate translocases in the mitochondrial outer membrane (TOM complex) and in the inner membrane (TIM complex) facilitate recognition of preproteins and transport across the two membranes [7].
• These T cell subsets are primarily differentiated on the basis of the cytokines that they produce, however, we have identified a novel gene family called TIM (T cell, immunoglobulin, mucin domain-containing molecules), whose members are differentially expressed on Th1 and Th2 cells [8].
• Genomic association of the TIM family and polymorphisms in both Tim-1 and Tim-3 in different immune-mediated diseases suggest that the family may have an important role in regulating immunity, both in terms of normal immune responses and in diseases like autoimmunity and asthma [8].
• These additional TPI gene introns are also required for the efficient removal of intron 6 [9].
• Protein translocation into mitochondria: the role of TIM complexes [10].

Chemical compound and disease context of TPI1

• Triosephosphate isomerase (TPI; D-glyceraldehyde-3-phosphate ketolisomerase [E.C.5.3.1.1]) deficiency is an autosomal recessive disorder that typically results in chronic, nonspherocytic hemolytic anemia and in neuromuscular impairment [11].
• The molecules discussed in this review include some of the leading vaccine candidates in schistosomiasis: the glutathione S-transferases, triose-phosphate isomerase, glyceraldehyde-3-phosphate dehydrogenase and the 23 and 25 kDa surface integral membrane proteins [12].
• A patient with triosephosphate isomerase (TPI) deficiency exhibited worsening of abnormal involuntary movements of the dystonic type and developed psychiatric symptoms while on selegiline [13].
• We produced the Taenia solium triosephosphate isomerase (TPI) in Escherichia coli and compared its biochemical and immunological properties with those of the commercial TPI from Sus scrofa [14].
• Previously, we showed that it is possible to introduce triose phosphate isomerase activity into the ribose-binding protein of Escherichia coli by constructing 17 mutations in the first two layers of residues that surround the wild-type ligand-binding site [15].

Biological context of TPI1

• The findings suggest that TPI and GAPDH may be candidate Ags for an autoimmune response to neurons and axons in MS [1].
• Phylogenetic analyses show that mitochondrial GAPDH and its N-terminal TPI fusion branch deeply within their respective eukaryotic protein phylogenies, suggesting that diatom mitochondria may have retained an ancestral state of glycolytic compartmentation that existed at the onset of mitochondrial symbiosis [16].
• The difference in K(m) is indicative of the difference in the active site of the human and M. tuberculosis TPI, which can be exploited for drug designing specifically targeting M. tuberculosis TPI [2].
• Triosephosphate isomerase (TPI), one of the key enzymes of the glycolytic pathway, is an attractive drug target against Mycobacterium tuberculosis as glycolysis provides the majority of the organism's energy requirements inside macrophages [2].
• Mitochondrial and Tpi genealogies are consistent with reciprocal monophyly, whereas sympatric populations of the species in Panama share identical or similar Mpi and Ci haplotypes, giving rise to genealogical polyphyly at the species level despite evidence for rapid sequence divergence at these genes between geographic races of H. melpomene [17].

Anatomical context of TPI1

• The efficacy order of TPI binding to microtubules is propositus > brother without neurological disorder > normal control [18].
• Our present studies with purified TPI and hemolysates revealed the binding of TPI, and the binding of human wild-type and mutant TPIs in hemolysate, to the red cell membrane, and the interference of binding with other hemolysate proteins [18].
• The interaction of cofilin with triose-phosphate isomerase as well as Na,K-ATPase was confirmed by immunoprecipitation and confocal microscopy in HeLa cells [19].
• Here, we show that diatoms--photosynthetic protists that acquired their plastids through secondary symbiotic engulfment of a eukaryotic rhodophyte--possess an additional isoenzyme each of both GAPDH and TPI [16].
• Surprisingly, these new forms are expressed as an TPI-GAPDH fusion protein which is imported into mitochondria prior to its assembly into a tetrameric bifunctional enzyme complex [16].

Associations of TPI1 with chemical compounds

• Importantly, the apparent K(m) value of M. tuberculosis rTPI for the substrate glyceraldehyde-3-phosphate is 84 muM which is sevenfold higher than the value reported for human TPI [2].
• Although this substitution conserves the overall charge of amino acid-104, the x-ray crystal structure of chicken TPI indicates that the loss of a side-chain methylene group (-CH2CH2COO- ---- -CH2COO-) is sufficient to disrupt the counterbalancing of charges that normally exists within a hydrophobic pocket of the native enzyme [4].
• The glutamate-to-aspartate substitution results in a thermolabile enzyme as demonstrated by assays of TPI activity in cultured fibroblasts of each patient and cultured Chinese hamster ovary (CHO) cells that were stably transformed with the mutant alleles [4].
• Reduction of this material using phosphoglycerate kinase/ATP, glyceraldehyde-3-phosphate dehydrogenase/NADH, triose-phosphate isomerase, and glycerol-phosphate dehydrogenase/NADH produces glycerol 3-[18O]phosphorothioate, which is subjected to ring closure using diethylphosphorochloridate [20].
• Two hTIM mutants were produced, in which a glutamine residue was substituted for either Met14 or Arg98, both of which are interface residuces [21].

Physical interactions of TPI1

• The crystal structure of leishmania triosephosphate isomerase (TIM) complexed with 2-(N-formyl-N-hydroxy)-aminoethyl phosphonate (IPP) highlights the importance of Asn11 for binding and catalysis [22].

Other interactions of TPI1

• Both GAPD and TPI1 do not have conserved E boxes but are induced and bound by Myc through regions with noncanonical E boxes [23].
• Two scFv-Abs generated from the CSF and from lesions of a MS brain showed immunoreactivity to TPI and GAPDH, respectively [1].
• Furthermore, the occurrence of autoantibodies against Tim and MnSOD was evaluated by ELISA in an additional 40 LSC patients, 30 other types of cancer (OTC) patients, and 50 noncancer controls (NC) [3].
• The gene for the peroxisomal targeting signal import receptor (PXR1) is located on human chromosome 12p13, flanked by TPI1 and D12S1089 [24].
• Identification of the origin of a 22p+ chromosome by triplex dosage effect of LDH B, GAPHD, TPI and ENO2 [25].

Analytical, diagnostic and therapeutic context of TPI1

• The M. tuberculosis TPI had a pH optimum in the range of 6-8 and a temperature optimum around 37 degrees C. Circular dichroism spectra analysis revealed that loss of secondary structure of rTPI occurs around 60 degrees C. Metal cations were not required for M. tuberculosis TPI activity [2].
• Crystals of human triosephosphate isomerase with two crystal morphologies were obtained using the normal vapour-diffusion technique with identical crystallization conditions [26].
• Analysis of a radiation hybrid panel for chromosome 12 with a PXR1 gene-based sequence-tagged site (STS) mapped the PXR1 gene between TPI1 and D12S1089 [24].
• Human triosephosphate isomerase (hTIM), a dimeric enzyme, was altered by site-directed mutagenesis in order to determine whether it can be dissociated into monomers [21].
• Similarly, results obtained in phase-partitioning and isoelectric-focusing experiments indicate physical interaction between aldolase and triose-phosphate isomerase (EC 5.3.1.1) [27].

References