Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.2.1.13 (glyceraldehyde-3-phosphate dehydrogenase)
6,511 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The behaviour and properties of membrane-bound GAPDH of rabbit reticulocytes were investigated. 2. The bound GAPDH is more resistant to inactivation by KCl than the soluble enzyme (allotopy). 3. The bound enzyme is released by electrolytes. This effect does not only depend on the ionic strength but additionally on the kind of ions, pH-value and protein concentration. 4. A comparison of the releasing effect of NAD analogues shows the necessity of the 5'-AMP moiety in the structure of the effector. 5. The represented results demonstrate the specifity of the GAPDH-membrane binding in rabbit reticulocytes.
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PMID:Further characterization of the association of glyceraldehyde-3-phosphate dehydrogenase with reticulocyte membranes. 0 Aug 80

Nicotinamide-(S-methylmercury-thioinosine) dinucleotide was formed by reaction of nicotinamide-(6-thiopurine) dinucleotide with methylmercury chloride. The compound exhibits coenzyme properties in the test with LDH (Km=1.5 X 10(-4) M, Vmax=12500) and LADH (Km=1.7 X 10(-4) M, Vmax=27) and inactivates YADH and GAPDH. From incubations with LDH and LADH the mercury containing coenzyme could be regarded by column be qualified for the X-ray structure analysis of the coenzyme-enzyme complex for some dehyrogenases based on the proportion of the heavy metal.
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PMID:Reactions of essential sulfhydryl residues of dehydrogenases with nicotinamide-(S-methylmercury-thioinosine) dinucleotide. 17 96

The stress of chronic hypobaric hypoxia present at high altitudes induces a series of adaptive changes in the intermediate metabolism in erythrocytes of high-altitude natives. Aymaras of the high Andean Plateau are shown to have within erythrocytes: (a) increased activity of NADH2 (GAPDH) generating stages, (b) decreased activity of NADH2 (LDH) consuming steps, (c) significantly increased methaemoglobin content, and (d) a large increase in the level of reduced glutathione. These alterations occur also in persons of the same ethnic group residing at low altitude. There is, however, only a moderate elevation of classic haematological parameters (erythrocyte count, haemoglobin and haematocrit) in highland natives. The functional implications of these metabolite changes are discussed with respect to regulation of erythrocyte metabolism.
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PMID:Methaemoglobin and erythrocyte reducing systems in high-altitude natives. 58 58

8 and 24 hours after alloxan administration, diabetic rat brain shows decreased glycogen content, significantly increased FDP, triose phosphates, pyruvate and lactate levels, a large rise in glucose and a 27% activation of anaerobic lactate production from glycogen. 48 hours after alloxan administration there is a recovery of glycogen and a fall in lactate levels. ATP and AMP levels are unchanged 8 and 24 hours after alloxan administration but the former is increased and the latter decreased 48 hours posttreatment. Insulin given to rats 8 hours after alloxan treatment reverses glycogen, FDP, triose phosphates, pyruvate and lactate levels seen in the diabetic rat brain. In addition the increament in glucose is reduced by half and the rate of anaerobic lactate formation from glycogen is restored to control values. G-6-P levels, unaffected by alloxan or insulin alone, are significantly lowered in animals which received insulin after alloxan. Phosphorylase, HK, PFK, ALD, GAPDH, PK, LDH and Glycogen synthetase activities are not modified in rat brain by administration of alloxan or insulin or both.
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PMID:Effect of alloxan and insulin on carbohydrate metabolism in rat brain. 73 60

As a contribution to the mechanisms of photochemotherapy, human skin homogenates were irradiated in the presence or absence of methoxsalen. The changes induced in LDH-, G-6-PDH-, GAPDH-, and GOT-activities were registered. Methoxsalen (50 mug/ml) failed to produce any significant effect. On pure G-6-PDH, methoxsalen exhibited a photoprotective action.
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PMID:The mechanism of photochemotherapy. 95 27

All-trans retinoic acid and its derivative retinoid, two new compounds with expanding therapeutic spectrum in dermatology, were investigated in biochemical assays. Both substances provoke an increase in oxygen consumption of rat skin whereas in human skin only retinoid was found active in this respect. In resting yeast cells, both substances failed to exert any significant influence on oxygen consumption.--Pure G-6-PDH was inhibited by retinoic acid and retinoid in concentrations as low as 5 mug/ml. In human skin homogenates, LDH-, GAPDH-, and G-6-PDH-activities were inhibited by retinoic acid whereas GOT-, LAP-, and ALD-activites remained practically unchanged following an incubation with retinoic acid in concentrations between 1 and 100 mug/ml for 60 min.--The data collected in this study were briefly discussed with regard to the use of retinoic acid and its derivatives in psoriasis.
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PMID:Influences of retinoic acid and retinoid on skin metabolism. Investigations of oxygen consumption and enzymatic activities of human skin. 98 76

High hydrostatic pressure inhibits growth in most organisms; this may be explained by a deactivation of enzymes involved in essential metabolic pathways. In order to check this hypothesis the enzymic activity of rabbit muscle lactic dehydrogenase and yeast glyceraldehyde-3-phosphate dehydrogenase was investigated in the presence of the coenzyme and excess of substrate at pressures up to 2kbar. Kinetic analysis of an initial phase of pressure induced activation and of a second phase of reversible deactivation shows that the two enzymes respond to high pressures in different ways leading to a volume of activation of increment V is not equal to (LDH) equal 0 plus or minus 1 cm-3 mol-1 and increment V is not equal to (GAPDH) equals 60 plus or minus 4 cm-3 mol-1, respectively. Comparing the lower limits of pressure deactivation, LDH is found to be more stable towards pressure than GAPDH. At p is approximately equal to 2 kbar total deactivation of both enzymes is observed. A concentration dependent lag of GAPDH reactivation proves dissocation to participate in the process of deactivation, while the effects for LDH are explicable on the basis of reversible denaturation alone.
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PMID:High pressure effects on the activity of glycolytic enzymes. 109 83

Using conditions that produced chronic inflammation in rat liver, we were able to find a correlation between induction of nitric oxide production and inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH; EC 1.2.1.12). This enzyme is a tetramer composed of identical M(r) 37,000 subunits. The tetramer contains 16 thiol groups, four of which are essential for enzymatic activity. Our information indicates that four thiol groups are S-nitrosylated by exposure to authentic nitric oxide (NO) gas. Furthermore, NO decreased GAPDH activity while increasing its auto-ADP-ribosylation. Reduced nicotinamide adenine dinucleotide and dithiothreitol are required for the S-nitrosylation of GAPDH caused by the NO-generating compound sodium nitroprusside. Our results suggests that a new and important action of nitric oxide on cells is the S-nitrosylation and inactivation of GAPDH. S-Nitrosylation of GAPDH may be a key covalent modification of multiple regulatory consequences in chronic liver inflammation.
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PMID:Nitric oxide-induced S-nitrosylation of glyceraldehyde-3-phosphate dehydrogenase inhibits enzymatic activity and increases endogenous ADP-ribosylation. 128 Nov 50

The steady-state level of the neuromodulin transcript in the neuron-like N1E-115 cell line was measured with a method combining reverse transcription and the polymerase chain reaction (RT/PCR). Total RNA was isolated from N1E-115 cells and treated with DNAse to remove residual DNA; cDNA was synthesized from this RNA by priming with random hexamers. For PCR amplification, primers for neuromodulin were designed for regions of the coding sequence that were identical in mouse, rat, and human. In one approach (the 'ratio method'), variations in RNA yield and cDNA synthesis efficiency were controlled for by amplifying a reference (housekeeping) gene (glyceraldehyde phosphate dehydrogenase; GAPDH). To control for inter-experimental variations in PCR amplification efficiencies the data were analyzed on semi-logarithmic plots, with which the relative levels of the starting templates could be determined by extrapolating the plots to cycle number zero (0). In another approach with RT/PCR (the 'spiking method'), the absolute level of N1E-115 neuromodulin cDNA was assessed by adding known amounts of cloned human neuromodulin template to the RT/PCR assay of N1E-115 nucleic acid and comparing the increased yield of product across cycles. When the spike was added at either the cDNA level (in the form of double-stranded DNA) or at the total RNA level (as sense RNA), the levels of N1E-115 calculated were virtually the same: 509 fg and 495 fg of coding region per ug total RNA in confluent N1E-115 cells, respectively. Treatment of N1E-115 cells with 2% dimethylsulfoxide for three days elevated neuromodulin mRNA levels 5.6-fold. Conversely, treatment of N1E-115 cells with 100 nM phorbol myristate acetate for 24 h decreased the level of neuromodulin mRNA by 70%. Under carefully controlled conditions and within certain limits of precision, the RT/PCR method appears to be suitable for assessing the level of low abundance mRNA under various pharmacologically-induced conditions.
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PMID:Transcriptional regulation of neuromodulin (GAP-43) in mouse neuroblastoma clone N1E-115 as evaluated by the RT/PCR method. 137 7

Multiple elements in the upstream region of the GAPDH gene play a role in mediating the acute and chronic effect of insulin on GAPDH gene expression. The complexity of this regulation provides many layers of control. In differentiated tissues, the transcriptional response to insulin results from the additive effects of g/TRE, IRE-A and IRE-B. The gTRE may interact with newly synthesized c-fos/c-jun heterodimer to activate GAPDH gene transcription. Studies are underway to determine whether protein synthesis inhibitors affect the regulation of GAPDH. Because there are several elements that mediate the effect, it will be difficult to determine the significance of these findings until each cis-acting factor and its binding protein can be studied in isolation. IRE-A and IRE-B act together to promote a 5- to 8-fold insulin effect on HGAPDH-CAT in H35 hepatoma cells and a 3-fold effect in 3T3 adipocytes. We have succeeded in detecting an insulin-sensitive DNA-binding protein referred to as IREA-BP with an element -480 to -435. Insulin treatment of differentiated 3T3 adipocytes for 1 hr results in a 4-fold increase in the amount of this binding protein, as estimated by the amount of 32P-labelled oligonucleotide retarded on non-denaturing PAGE (11). The effect of insulin on IRP-B is comparable. Furthermore, IREA-BP is induced during the process of fasting and refeeding rats, an important in vivo correlate with our tissue culture models (11). These observations imply that the binding proteins IREA-BP and IRP-B are essential components in the signal transduction pathway of insulin action on GAPDH gene expression in metabolically active tissues such as fat and liver. Differentiation-dependence and tissue-specificity are achieved through multiple regulatory elements and involve pre- and post-translational regulation of multiple transcription factors. IREA-BP is present in preadipocytes but activity in highly induced upon differentiation of preadipocytes to adipocytes. The IRE-B (-408 to -269) DNA binding protein is not detected in 3T3 preadipocytes. A gC/EBP like-protein takes part in the formation of this complex which may explain the inductive effect of differentiation on binding. Finally, footprint and cotransfection studies indicate that the differentiation-dependent protein C/EBP also regulates GAPDH gene transcription through a motif located within one hundred nucleotides of the promoter. We have begun to clone the IRE-A and IRE-B DNA binding proteins. An IRE-A binding protein that footprints the 3' domain of the IRE-A has been cloned.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Multiple insulin-responsive elements regulate transcription of the GAPDH gene. 138 8


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