Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.2.1.13 (glyceraldehyde-3-phosphate dehydrogenase)
6,511 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obesity-related diseases such as the metabolic syndrome and type 2 diabetes originate, in part, from the progressive metabolic deterioration of skeletal muscle. A preliminary proteomic survey of rectus abdominus muscle detected a statistically significant increase in adenylate kinase (AK)1, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and aldolase A in obese/overweight and morbidly obese women relative to lean control subjects. AK1 is essential for the maintenance of cellular energy charge, and GAPDH and aldolase A are well known glycolytic enzymes. We found that muscle AK1 protein and enzymatic activity increased 2.9 and 90%, respectively, in obese women and 9.25 and 100%, respectively, in morbidly obese women. The total enzymatic activity of creatine kinase, which also regulates energy metabolism in muscle, was shown to increase 30% in obese/overweight women only. We propose that increased protein and enzymatic activity of AK1 is representative of a compensatory glycolytic drift to counteract reduced muscle mitochondrial function with the progression of obesity. This hypothesis is supported by increased abundance of the glycolytic enzymes GAPDH and aldolase A in obese and morbidly obese muscle. In summary, proteome analysis of muscle has helped us better describe the molecular etiology of obesity-related disease.
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PMID:Proteome analysis of skeletal muscle from obese and morbidly obese women. 1585 11

S-Nitrosation of protein sulfhydryl groups is an established response to oxidative/nitrosative stress. The transient nature and reversibility of S-nitrosation, as well as its specificity, render this posttranslational modification an attractive mechanism of regulation of protein function and signal transduction, in analogy to S-glutathionylation. Several feasible mechanisms for protein S-nitrosation have been proposed, including transnitrosation by S-nitrosothiols, such as S-nitrosoglutathione (GSNO), where the nitrosonium moiety is directly transferred from one thiol to another. The reaction between GSNO and protein sulfhydryls can also produce a mixed disulfide by S-glutathionylation, which involves the nucleophilic attack of the sulfur of GSNO by the protein thiolate anion. In this study, we have investigated the possible occurrence of S-glutathionylation during reaction of GSNO with papain, creatine phosphokinase, glyceraldehyde-3-phosphate dehydrogenase, alcohol dehydrogenase, bovine serum albumin, and actin. Our results show that papain, creatine phosphokinase, and glyceraldehyde-3-phosphate dehydrogenase were significantly both S-nitrosated and S-glutathionylated by GSNO, whereas alcohol dehydrogenase, bovine serum albumin, and actin appeared nearly only S-nitrosated. The susceptibility of the modified proteins to denitrosation and deglutathionylation by reduced glutathione was also investigated.
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PMID:S-nitrosation versus S-glutathionylation of protein sulfhydryl groups by S-nitrosoglutathione. 1599 48

Hormone-sensitive lipase (HSL), a key enzyme in fatty acid mobilization in adipocytes, has been demonstrated also in skeletal muscle. To gain further insight into the role and importance of HSL in skeletal muscle, a transcriptome analysis of soleus muscle of HSL-null mice was performed. A total of 161 transcripts were found to be differentially expressed. Increased mRNA levels of fructose-1,6-bisphosphatase, fructose-2,6-bisphosphatase, and phosphorylase kinase gamma1A suggest a higher glycogen flux in soleus muscle of HSL-null mice. An observed increase in the utilization of glycogen stores supports this finding. Moreover, an increased amount of intramyocellular lipid droplets, observed by transmission electron microscopy, suggests decreased mobilization of lipid stores in HSL-null mice. To complement the transcriptome data, protein expression analysis was performed. Five spots were found to be differentially expressed: pyruvate dehydrogenase E1alpha, creatine kinase (CK), ankyrin-repeat domain 2, glyceraldehyde-3-phosphate dehydrogenase, and one protein yet to be identified. The increased protein level of CK indicates creatine phosphate degradation to be of increased importance in HSL-null mice. The results of this study suggest that in the absence of HSL, a metabolic switch from reliance on lipid to carbohydrate energy substrates takes place, supporting an important role of HSL in soleus muscle lipid metabolism.
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PMID:Transcriptome and proteome analysis of soleus muscle of hormone-sensitive lipase-null mice. 1619 3

Hypochlorous acid (HOCl) and chloramines are produced by the neutrophil enzyme, myeloperoxidase. Both react readily with thiols, although chloramines differ from HOCl in discriminating between low molecular weight thiols on the basis of their pKa. Here, we have compared the reactivity of HOCl and taurine chloramine with thiol proteins by examining inactivation of creatine kinase (CK) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). With both enzymes, loss of activity paralleled thiol loss. For CK both were complete at a 1:1 taurine chloramine:thiol mole ratio. For GAPDH each chloramine oxidized two thiols. Three times more HOCl than taurine chloramine was required for inactivation, indicating that HOCl is less thiol specific. Competition studies showed that thiols of CK were 4 times more reactive with taurine chloramine than thiols of GAPDH (rate constants of 1200 and 300 M-1s-1 respectively). These compare with 205 M-1s-1 for cysteine and are consistent with their lower pKa's. Both enzymes were equally susceptible to HOCl. GSH competed directly with the enzyme thiols for taurine chloramine and protected against oxidative inactivation. At lower GSH concentrations, mixed disulfides were formed. We propose that chloramines should preferentially attack proteins with low pKa thiols and this could be important in regulatory processes.
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PMID:Taurine chloramine is more selective than hypochlorous acid at targeting critical cysteines and inactivating creatine kinase and glyceraldehyde-3-phosphate dehydrogenase. 1633 78

Changes in surface hydrophobicity are generally considered as a sensitive indicator for monitoring the structural alterations of proteins that are often associated with changes in function. Currently, no technique has been developed to screen a complex mixture of proteins for changes in the conformation of specific proteins. In this study, we adapted a UV photolabeling approach, using an apolar fluorescent probe, 4,4'-dianilino-1,1'-binaphthyl-5,5'-disulfonic acid (BisANS), to monitor changes in surface hydrophobic domains in either purified rhodanese or skeletal muscle cytosolic proteins by urea-induced unfolding or in response to in vitro metal-catalyzed oxidation. Using two-dimensional polyacrylamide gel electrophoresis (2D PAGE), we identified two specific proteins in skeletal muscle cytosol that exhibited a marked loss of incorporation of BisANS after exposure to in vitro oxidative stress: creatine kinase (CK) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). We found that the activities of both enzymes were also reduced significantly in response to oxidative stress. We then determined if this method could detect changes in surface hydrophobicity in specific proteins arising from oxidative stress generated in vivo by muscle denervation. A loss in surface hydrophobic domains in CK and GAPDH was again observed as measured by the BisANS photoincorporation approach. In addition, the CK and GAPDH activity in denervated muscle was markedly reduced. These data demonstrate for the first time that this assay can screen a complex mixture of proteins for alterations in surface hydrophobic domains of individual proteins.
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PMID:A novel approach for screening the proteome for changes in protein conformation. 1650 63

Peroxisome proliferator-activated receptor-gamma coactivator-1alpha and -1beta (PGC-1alpha and PGC-1beta) were overexpressed by adenovirus-mediated gene transfer in cultures of primary rat skeletal muscle cells derived from neonatal myoblasts. Effects on muscle fiber type transition and metabolism were studied from days 5 to 22 of culture. PGC-1alpha and PGC-1beta overexpression caused a three- to fourfold increase in mRNA level, a doubling of enzymatic activity of citrate synthase, a slight increase in short-chain acyl-CoA dehydrogenase mRNA, a doubling of the mRNA level, and a 30-50% increase in enzymatic activity of glyceraldehyde-3-phosphate dehydrogenase. Lactate dehydrogenase or creatine kinase activity was unchanged. PGC-1alpha enhanced glycogen buildup twofold at 5 or 25 mM glucose, whereas PGC-1beta caused a decrease. Both PGC-1alpha and PGC-1beta overexpression caused a faster maturation of myotubes, as seen by mRNA downregulation of the immature embryonal and perinatal myosin heavy-chain (MHC) isoforms. PGC-1alpha or PGC-1beta overexpression enhanced mRNA of the slow oxidative-associated MHC isoform MHCIb and downregulated mRNA levels of the fast glycolytic-associated MHC isoforms MHCIIX and MHCIIB. Only PGC-1beta overexpression caused an increase in mRNA of the intermediary fast oxidative-associated MHC isoform MHCIIA. PGC-1alpha or PGC-1beta overexpression upregulated GLUT4 mRNA and downregulated myocyte enhancer factor 2C transcription factor mRNA; only PGC-1alpha overexpression caused an increase in the mRNA expression of TRB3, a negative regulator of insulin signaling. These results show that both PGC-1alpha and PGC-1beta are involved in the regulation of skeletal muscle fiber transition and metabolism and that they have both overlapping and differing effects.
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PMID:PGC-1alpha and PGC-1beta have both similar and distinct effects on myofiber switching toward an oxidative phenotype. 1672 Jun 25

Aging and age-related disorders such as Alzheimer's disease (AD) are usually accompanied by oxidative stress as one of the main mechanisms contributing to neurodegeneration and cognitive decline. Aging canines develop cognitive dysfunction and neuropathology similar to those seen in humans, and the use of antioxidants results in reductions in oxidative damage and in improvement in cognitive function in this canine model of human aging. In the present study, the effect of a long-term treatment with an antioxidant-fortified diet and a program of behavioral enrichment on oxidative damage was studied in aged canines. To identify the neurobiological mechanisms underlying these treatment effects, the parietal cortex from 23 beagle dogs (8.1-12.4 years) were treated for 2.8 years in one of four treatment groups: i.e., control food-control behavioral enrichment (CC); control food-behavioral enrichment (CE); antioxidant food-control behavioral enrichment (CA); enriched environment-antioxidant-fortified food (EA). We analyzed the levels of the oxidative stress biomarkers, i.e., protein carbonyls, 3-nitrotyrosine (3-NT), and the lipid peroxidation product, 4-hydroxynonenal (HNE), and observed a decrease in their levels on all treatments when compared to control, with the most significant effects found in the combined treatment, EA. Since EA treatment was most effective, we also carried out a comparative proteomics study to identify specific brain proteins that were differentially expressed and used a parallel redox proteomics approach to identify specific brain proteins that were less oxidized following EA. The specific protein carbonyl levels of glutamate dehydrogenase [NAD (P)], glyceraldehyde-3-phosphate dehydrogenase (GAPDH), alpha-enolase, neurofilament triplet L protein, glutathione-S-transferase (GST) and fascin actin bundling protein were significantly reduced in brain of EA-treated dogs compared to control. We also observed significant increases in expression of Cu/Zn superoxide dismutase, fructose-bisphosphate aldolase C, creatine kinase, glutamate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase. The increased expression of these proteins and in particular Cu/Zn SOD correlated with improved cognitive function. In addition, there was a significant increase in the enzymatic activities of glutathione-S-transferase (GST) and total superoxide dismutase (SOD), and significant increase in the protein levels of heme oxygenase (HO-1) in EA treated dogs compared to control. These findings suggest that the combined treatment reduces the levels of oxidative damage and improves the antioxidant reserve systems in the aging canine brain, and may contribute to improvements in learning and memory. These observations provide insights into a possible neurobiological mechanism underlying the effects of the combined treatment. These results support the combination treatments as a possible therapeutic approach that could be translated to the aging human population who are at risk for age-related neurodegenerative disorders, including Alzheimer's disease.
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PMID:Proteomic identification of brain proteins in the canine model of human aging following a long-term treatment with antioxidants and a program of behavioral enrichment: relevance to Alzheimer's disease. 1705 14

We have characterized the global gene expression profile in left vastus lateralis muscles of sprinters and sedentary men. The gene expression profile was analyzed by using serial analysis of gene expression (SAGE) method. The abundantly expressed transcripts in the sprinter's muscle were mainly involved in contraction and energy metabolism, whereas six transcripts were corresponding to potentially novel transcripts. Thirty-eight transcripts were differentially expressed between the sprinter and sedentary individuals. Moreover, sprinters showed higher expressions of both uncharacterized and potentially novel transcripts. Sprinters also highly expressed seven transcripts, such as glycine-rich protein, myosin heavy polypeptide (MYH) 2, expressed sequence tag similar to (EST) fructose-bisphosphate aldolase 1 isoform A (ALDOA), glyceraldehyde-3-phosphate dehydrogenase and ATP synthase F0 subunit 6. On the other hand, 20 transcripts such as MYH1, tropomyosin 2 and 3, troponin C slow, C2 fast, I slow, T1 slow and T3 fast, myoglobin, creatine kinase, ALDOA, glycogen phosphorylase, cytochrome c oxidase II and III, and NADH dehydrogenase 1 and 2 showed lower expression levels in the sprinters than the sedentary controls. The current study has characterized the global gene expressions in sprinters and identified a number of transcripts that can be subjected to further mechanistic analysis.
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PMID:Gene expression profile of sprinter's muscle. 1761 33

Characterisation and identification of peptides (800 to 5000 Da) generated by intestinal digestion of fish or meat were performed using MS analyses (matrix-assisted laser desorption ionisation time of flight and nano-liquid chromatography electrospray-ionisation ion trap MS/MS). Four pigs fitted with cannulas at the duodenum and jejunum received a meal exclusively made of cooked Pectoralis profundus beef meat or cooked trout fillets. A protein-free meal, made of free amino acids, starch and fat, was used to identify peptides of endogenous origin. Peptides reproducibly detected in digesta (i.e. from at least three pigs) were evidenced predominantly in the first 3 h after the meal. In the duodenum, most of the fish- and meat-derived peptides were characteristic of a peptic digestion. In the jejunum, the majority of peptides appeared to result from digestion by chymotrypsin and trypsin. Despite slight differences in gastric emptying kinetics and overall peptide production, possibly in relation to food structure and texture, six and four similar peptides were released after ingestion of fish or meat in the duodenum and jejunum. A total of twenty-six different peptides were identified in digesta. All were fragments of major structural (actin, myosin) or sarcoplasmic (creatine kinase, glyceraldehyde-3-phosphate dehydrogenase and myoglobin) muscle proteins. Peptides were short ( < 2000 Da) and particularly rich in proline residues. Nineteen of them contained bioactive sequences corresponding mainly to an antihypertensive activity. The present work showed that after fish or meat ingestion, among the wide variety of peptides produced by enzymic digestion, some of them can be reproducibly observed in intestinal digesta.
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PMID:Peptides reproducibly released by in vivo digestion of beef meat and trout flesh in pigs. 1776 98

Hagfish, the plesiomorphic sister group of all vertebrates, are deep-sea scavengers. The large musculus (m.) longitudinalis linguae (dental muscle) is a specialized element of the feeding apparatus that facilitates the efficient ingestion of food. In this article, we compare the protein expression in hagfish dental and somatic (the m. parietalis) skeletal muscles via two-dimensional gel electrophoresis and mass spectrometry in order to characterize the former muscle. Of the 500 proteins screened, 24 were identified with significant differential expression between these muscles. The proteins that were overexpressed in the dental muscle compared to the somatic muscle were troponin C (TnC), glycogen phosphorylase, beta-enolase, fructose-bisphosphate aldolase A (aldolase A), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In contrast, myosin light chain 1 (MLC 1) and creatine kinase (CK) were over-expressed in the somatic muscle relative to the dental muscle. These results suggest that these two muscles have different energy sources and contractile properties and provide an initial representative map for comparative studies of muscle-protein expression in low craniates.
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PMID:Differential proteome analysis of hagfish dental and somatic skeletal muscles. 1796 21


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