Disease relevance of GAPDH

• The DNA sequence contained an open reading frame encoding for a 336 amino acid polypeptide exhibiting 95% sequence identity with the GAPDH from Streptococcus pyogenes and from other streptococci [1].
• Using the Qiaexpress expression plasmids, the gapdh gene was inducibly overexpressed in E. coli to produce GAPDH with a hexahistidyl N-terminus to permit its purification [1].
• The more potent inhibitory activity against angiotensin-converting enzyme (ACE) was excised from a glyceraldehyde-3-phosphate dehydrogenase (GAPDH) preparation of Bacillus stearothermophilus by heating at 120 degrees C in 1 M AcOH-20 mM HCl, as compared with GAPDH preparations of yeast and pig [2].
• Failure of glycolysis to increase sufficiently to supply optimal levels of energy production in ischemic heart muscle is due in part to the cummulative restrainst of acidosis on rate-limiting enzymes, particularly glyceraldehyde-3-phosphate dehydrogenase [3].
• LAD/LADc ratios were increased for hexokinase (1.69), phosphofructokinase (3.69), and glyceraldehyde-3-phosphate dehydrogenase (2.29) in the ischemia heart and for phosphofructokinase (3.90), glyceraldehyde-3-phosphate dehydrogenase (2.20), GLUT 4 (1.55) and GLUT 1 (2.20) in the ischemia/reflow heart [4].

High impact information on GAPDH

• The effect of glucose on sarcolemmal K(ATP) channels was mediated by the catalytic activity of glyceraldehyde-3-phosphate dehydrogenase and consequent generation of 1,3-bisphosphoglycerate [5].
• These systems are analogous to, but more complex than, those in glyceraldehyde-3-phosphate dehydrogenase and papain where a single thiol and a histidine residue in a relatively apolar milieu form a thiolate-imidazolium ion pair which is favored over the thiol-imidazole prototropic tautomer [6].
• Strong transcriptional activity was found for the ubiquitin and heat shock protein (hsp27, hsp70) genes, and for PAI-1 and GAPDH [7].
• Amino acid sequence analysis of the radioactive peptide gave Ile-Val-Ser-Asn-Ala-Ser-X-Thr-Thr-Asn-(...). This sequence is identical to the highly conserved region from Ile-143 to Asn-152 in pig muscle GAPDH, except for the active site Cys-149 to which the tetrahydropentalenolactone was covalently bound [8].
• Molecular modeling was used to compare both pentalenolactone (3) and heptelidic acid (4), a mechanistically related inactivator of GAPDH, with the normal substrate, glyceraldehyde 3-phosphate (1) [8].

Chemical compound and disease context of GAPDH

• Glucose consumption was reduced from 483 (before ischemia) to 242 mumol/hr per g (P less than 0.005) and inhibition at glyceraldehyde-3-phosphate dehydrogenase was again noted [9].
• Succinylation of glyceraldehyde-3-phosphate dehydrogenase from Bacillus stearothermophilus. A reactive threonine residue in the apoenzyme [10].
• Bacillus stearothermophilus glyceraldehyde-3-phosphate dehydrogenase as a source of angiotensin-converting enzyme inhibitors [2].

Biological context of GAPDH

• Regardless of the transformation or editing procedures for outliers applied, there was negligible genetic variation for the expression of target genes relative to GAPDH [11].
• The GAPDH protein of S. suis seems to be involved in the first steps of the bacterial adhesion to host cells [1].
• Because adhesion to host cells may be important in the carrier state, this study was undertaken to characterize a 39 kDa surface protein identified as a glyceraldehyde-3-phosphate dehydrogenase (GAPDH), possibly implicated in the adhesion of the bacteria [1].
• One of the B. stearothermophilus ACE inhibitors BG-1, was the GAPDH peptide 68-77 (Gly-Lys-Glu-Ile-Ile-Val-Lys-Ala-Glu-Arg, IC50: 32 microM) [2].
• In comparison to the amino acid sequence of glyceraldehyde-3-phosphate dehydrogenase from other species, this peptide is in a highly conserved region and is part of the active site of the enzyme [12].

Anatomical context of GAPDH

• The rate of bundle formation, after addition of GAPDH to preformed microtubules, is not dependent on the GAPDH concentration [13].
• It is of interest that increases in mRNA levels over control values were also observed in adjacent aerobic heart muscle from intervention hearts, including 3.6- to 4.5-fold elevations in message for GAPDH and a 2.1-fold increase in signal for pyruvate dehydrogenase [14].
• Specificity was tested by estimating the granulosa cell mRNA content of the constitutively expressed enzyme, glyceraldehyde-3-phosphate dehydrogenase [15].
• Extracts of glyceraldehyde 3-phosphate dehydrogenase that were obtained from boar spermatozoa incubated with (S)-alpha-chlorohydrin or (R,S)-3-chlorolactaldehyde showed significant reductions in their enzymic activity [16].
• Role of lysine residues in the binding of glyceraldehyde-3-phosphate dehydrogenase to human erythrocyte membranes [17].

Associations of GAPDH with chemical compounds

• Reduction of pentalenolactone with tritium gas gave [2,3,7,8-3H4]tetrahydropentalenolactone (7), which also exhibited time-dependent, irreversible inactivation of GAPDH [8].
• Incubation of rabbit muscle glyceraldehyde-3-phosphate dehydrogenase (GAPDH) with the antibiotic pentalenolactone (3) results in time-dependent, irreversible inhibition of GAPDH by modification of a single Cys residue in each subunit of the homotetrameric enzyme [8].
• Microsequencing analysis and fast atom bombardment mass spectrometry (FAB-MS) with collision-induced dissociation (CID) were used to characterize one of the adducts as APAP bound to the cysteinyl sulfhydryl group of Cys-149 in the active site peptide of GAPDH [18].
• Glycating agents, methylglyoxal (MG) and glyceraldehyde (Glyc), caused an increase in the formation of advanced glycation endproducts (AGEs) in native and denatured GAPDH and AAT [19].
• Another inhibitor, BG-2 (Gly-Lys-Met-Val-Lys-Val-Val-Ser-Trp-Tyr, IC50: 6 microM), correspond to GAPDH peptide 304-313 [2].

Other interactions of GAPDH

• Notably, PBMC derived from immune and naive pigs constitutively produced relatively high amounts of IL-10-specific mRNA, exceeding that of GAPDH mRNA, independently of the addition of viral antigen or the mitogen concanavalin A (Con A) [20].
• In contrast, mRNA levels coding for type I collagen, fibronectin and GAPDH (used as control of cellular activity) were not modified [21].
• This is a simple method that allows reliable determination of the differing regulation of cytokine mRNAs specific for porcine interleukin (IL)-2, -4 and -10, interferon gamma (IFN-gamma) and the housekeeping gene, GAPDH, as an endogenous control [20].
• To determine if suppression was at the level of IFN-alpha transcription, quantitative RT-PCR was performed for IFN-alpha mRNA and compared to GAPDH and cyclophilin mRNA quantification [22].
• The effect of MCWE on alveolar macrophage tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta) gene transcription, as determined by a reverse transcription-PCR assay standardized with the endogenous glyceraldehyde-3-phosphate dehydrogenase gene, was also investigated [23].

Analytical, diagnostic and therapeutic context of GAPDH

• Tryptic digestion of inactivated GAPDH and purification of the resultant products by reverse-phase HPLC gave a single labeled peptide [8].
• Bands were semiquantitated by comparison to an external standard (GAPDH) using band densitometry [24].
• Multiplex polymerase chain reaction (PCR) and competitive PCR were performed on aliquots of the cDNAs by using either endogenous (glyceraldehyde-3-phosphate dehydrogenase [G3PDH]) or exogenous sequence (PCR mimic for TGF-beta 1) as internal standards, respectively [25].
• Kinetic evidence for a reversible isomerization of pig muscle glyceraldehyde-3-phosphate dehydrogenase in its crystallization medium [26].
• The interaction of P8 from transformed fibroblasts and glyceraldehyde-3-phosphate dehydrogenase from hamster and rabbit muscle with DNA has been studied using a Millipore filtration technique [27].

References