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:1.1.1.37 (malate dehydrogenase)
4,591 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Enzyme activities operative in glucose degradation and citrate cleavage pathway were studied in the adipose tissue of twenty-four patients with adult-onset diabetes and normal body weight, aged 59+/-9 years, and twenty-four matched controls. In normal tissue, type II (heat-inactivated) hexokinase moderately predominated over type I (heat-resistant). 6-Phosphofructokinase had an extremely low activity, which was by far the lowest among the ten glycolytic enzyme activities investigated, and which therefore might greatly limit the glycolytic rate. The level of glucose-6-phosphate dehydrogenase and phosphogluconate dehydrogenase (decarboxylating) was elevated above that occurring in other tissues. This, especially if considered together with the low 6-phosphofructokinase activity, would suggest a major role of pentose cycle in glucose degradation. Of the citrate cleavage pathway enzymes, ATP citrate-lyase, although having a lower activity than malate dehydrogenase and malate dehydrogenase (decarboxylating) (NADP), was readily measurable, which contrasts with previous data by others. This finding is consistent with the occurrence of lipogenetic capacity in human adipose tissue. In diabetic tissue, there was a decreased activity, both on a protein and on a wet-weight basis, of enzymes concerned with the glucose entry into metabolic pathways, namely hexokinase (both type I and, especially, type II) and pentose cycle dehydrogenases, as well as of pyruvate kinase. This could be connected with the defective glucose utilization by adipose tissue in diabetes. Beside the above-mentioned dehydrogenases, malate dehydrogenase (decarboxylating) (NADP) was also diminished. The reduction of these NADPH-forming enzymes, which supply reducing equivalents for fatty acid synthesis, would suggest a depressed lipogenesis.
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PMID:Enzymes of glucose metabolism and of the citrate cleavage pathway in adipose tissue of normal and diabetic subjects. 118 27

Multiple genes for thioredoxins (TRX) have been demonstrated in Dictyostelium discoideum. We expressed the cDNA for one of these genes (DdTrx1) in E. coli and purified the protein to homogeneity. The interaction with classic substrates as well as TRX reductases was analysed. It reacted with every tested substrate: insulin, NADP-dependent malate dehydrogenase and fructose-1,6-bisphosphatase. With a S0.5 of 20 microM, the reactivity with the fructose-1,6-bisphosphatase is the highest ever found for a heterologous TRX. DdTRX1 itself is accepted as a substrate by the chloroplast ferredoxin-dependent TRX reductase, as well as by the E. coli NADPH-dependent TRX reductase. Thus, the Dictyostelium TRX is functionally promiscuous. Its reactivity with insulin, chloroplast NADP-dependent malate dehydrogenase and ferredoxin-dependent TRX reductase resemble those of other TRX. It is, however, clearly different in its good interaction with chloroplast fructose-1,6-bisphosphatase and in its poor interaction with E. coli NADP-dependent TRX reductase.
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PMID:Biochemical characterization of thioredoxin 1 from Dictyostelium discoideum. 133 May 54

The chloroplastic enzyme NADP-malate dehydrogenase is activated by a reversible thiol/disulfide interchange with reduced thioredoxin. Its target disulfide bridge is considered to be located at the amino terminus. To further substantiate the regulatory role of this disulfide, site-directed mutagenesis has been used to replace each or both of the amino-terminal cysteines of the sorghum leaf NADP-malate dehydrogenase, expressed in Escherichia coli, by serines. A truncation mutant lacking the amino terminus has also been produced. Surprisingly, the mutant proteins still required activation by reduced thioredoxin. However, their activation was almost instantaneous, whereas the native enzyme reached full activity after a 10-20 min preincubation. The 8 1/2 for reduced thioredoxin was decreased 2-fold in the mutants, but their Km values for NADPH and oxaloacetate did not change significantly. The inhibition of activation by NADP and inhibition of activity by thiol-derivatizing agents were also retained. These results are interpreted as an indication that two thioredoxin-dependent reduction steps are involved in NADP-dependent malate dehydrogenase light activation, hence that two disulfides per monomer participate in the process. The overall activation rate would depend on a conformational change following the reduction of the amino-terminal disulfide bridge. The amino terminus also plays a role in the dimerization of the protein.
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PMID:Site-directed mutagenesis reveals the involvement of an additional thioredoxin-dependent regulatory site in the activation of recombinant sorghum leaf NADP-malate dehydrogenase. 140 Apr 68

1. The component fatty acids of the endogenous phospholipids of microsomal preparations of Mucor, when shaken at 30 degrees C, increased in both chain length and in degree of unsaturation. The net effect was the production of gamma-linolenic acid which, over 2 h, increased from 17% to 32% of total fatty acids present. No further significant changes occurred after this time. 2. The major site for desaturation/elongation reactions was at the sn-2 position of PtdIns. PtdCho and PtdEtn were not implicated. 3. Of numerous metabolites and cofactors added to the microsomes, only malate could prolong the elongation/desaturation reactions for up to 6 h. This effect was shown to be due to a membrane-associated malic enzyme [malate dehydrogenase (decarboxylating) NADP+] with the NADPH produced being used in fatty-acid desaturation. 4. Kinetic analysis of cytosolic and microsomal enzymes [both in 0.1% (mass/vol.) Chaps] could not distinguish between them. However, when the microsomal malic enzyme was dialysed to remove Chaps, it lost 90% of activity, although the cytosolic malic enzyme lost only 20% activity. 5. The structural analogue of malate, tartronic acid, which is an inhibitor of malic enzyme, also inhibited the malate-induced stimulation of fatty-acyl group desaturation and elongation in the microsomal membranes. 6. It is concluded that two distinct malic enzymes exist, one soluble and one membrane bound, with similar active sites. Both have different roles in the production of NADPH, for lipid metabolism. The former will produce NADPH for fatty-acid biosynthesis whilst the latter produces NADPH for fatty-acid desaturation.
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PMID:Desaturation of polyunsaturated fatty acids in Mucor circinelloides and the involvement of a novel membrane-bound malic enzyme. 142 73

Injection with pharmacological doses of dexamethasone (5 mg/kg) and/or bovine glucagon (1 mg/kg) exerts pronounced effects on toadfish liver compared with vehicle-treated control fish. Affected parameters include hepatic levels of glycogen and the activities of glutamate dehydrogenase, aspartate aminotransferase, malate dehydrogenase, and enzymes involved in NADPH generation as well as the kinetics of pyruvate kinase. Activities of tyrosine aminotransferase, however, a prime target for hormonal induction in mammals, remain unchanged in Opsanus. In subsequently isolated toadfish hepatocytes, metabolite concentrations and flux through gluconeogenesis are altered as are in vitro responses to epinephrine and catfish glucagon in previously injected fish. Contrary to existing mammalian models, short-term regulation of urea cycle activity can be ruled out for toadfish, since hormone treatments fail to influence the activity of two ornithine-urea cycle enzymes or the rate of hepatocyte-urea synthesis. Treatment-dependent increases in hepatic glutamine synthetase, the unique feeder enzyme for ammonia "nitrogen" in fish urea cycle, indicate a potentially pivotal role for this enzyme in longer-term regulation of ureogenesis.
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PMID:Metabolic actions of glucagon and dexamethasone in liver of the ureogenic teleost Opsanus beta. 160 Dec 63

To gain some insight into the process by which both acetylCoA and NADPH, needed for fatty acid synthesis, are obtained, in the cytosol, from the effluxed intramitochondrial citrate, via citrate lyase and malate dehydrogenase plus malic enzyme respectively, the capability of externally added pyruvate to cause efflux of malate from rat liver mitochondria was tested. The occurrence of a pyruvate/malate translocator is here shown: pyruvate/malate exchange shows saturation features (Km and Vmax values, measured at 20 degrees C and at pH 7.20, were found to be about 0.25 mM and 2.7 nmoles/min x mg mitochondrial protein, respectively) and is inhibited by certain impermeable compounds. This carrier, together with the previously reported tricarboxylate and oxodicarboxylate translocators proved to allow for citrate and oxaloacetate efflux due to externally added pyruvate.
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PMID:Pyruvate/malate antiporter in rat liver mitochondria. 173 91

A new over-expression system has been set up for Escherichia coli thioredoxin, yielding 55 mg purified protein/10 g fresh cells. This system has been used to produce thioredoxin modified by site-directed mutagenesis. Taking advantage of the structural and enzymatic similarity between E. coli and spinach m-type thioredoxin, Asp61 of E. coli thioredoxin has been changed into Asn in order to investigate the impact of the suppression of a charged residue on the interaction of thioredoxin with target enzymes. The modification did not significantly alter the structure of the protein. Neither the rate of reduction of insulin and 5,5'-dithio-bis(2-nitrobenzoic acid) by the reduced thioredoxin, nor the reduction by NADPH-dependent thioredoxin reductase, have been modified. The major effect of the mutation was observed for chloroplast enzyme activation with thioredoxin reduced by dithiothreitol and with thioredoxin reduced by ferredoxin-dependent thioredoxin reductase in a light-activation reconstituted chloroplast system. The substitution of the negatively charged Asp61 by the neutral Asn led to an increase in the efficiency of spinach fructose-1,6-bisphosphatase activation by the dithiothreitol-reduced thioredoxin, and to an increase in both spinach fructose-1,6-bisphosphatase and corn NADP-dependent malate dehydrogenase activities in the light-activation system. This suggests that the suppression of the negative charge improves the reactivity of thioredoxin with chloroplast enzymes such as fructose-1,6-bisphosphatase and ferredoxin-dependent thioredoxin reductase.
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PMID:Mutation of a negatively charged amino acid in thioredoxin modifies its reactivity with chloroplastic enzymes. 184 15

Thioredoxin, reduced either enzymatically with NADPH and NADP-thioredoxin reductase or chemically with dithiothreitol, reduced alpha-amylase and trypsin inhibitor proteins from several sources. Included were cystine-rich seed representatives from wheat (alpha-amylase inhibitors), soybean (Bowman-Birk trypsin inhibitor), and corn (kernel trypsin inhibitor). This system also reduced other trypsin inhibitors: the soybean Kunitz inhibitor, bovine lung aprotinin, and egg white ovoinhibitor and ovomucoid proteins. The ability of these proteins to undergo reduction by thioredoxin was determined by 1) a coupled enzyme activation assay with chloroplast NADP-malate dehydrogenase or fructose-1,6-bisphosphatase, 2) a dye reduction assay with 5',5'-dithiobis(2-nitrobenzoic acid), and 3) a direct reduction method based on the fluorescent probe, monobromobimane, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Reduction experiments with the seed proteins were carried out with thioredoxin from wheat germ (h-type) or Escherichia coli; the corresponding experiments with the animal trypsin inhibitors were carried out with thioredoxin from calf thymus or E. coli. In all cases, thioredoxin appeared to act catalytically; the reduced form of glutathione was without effect. When considered in conjunction with earlier results on purothionin (confirmed and extended in the current study), the new findings suggest that the NADP/thioredoxin system functions in the reduction of protein inhibitors of seeds and animal tissues. These results also raise the question of the occurrence of glutaredoxin in plants, as E. coli glutaredoxin was found to promote the reduction of some but not all of the proteins tested.
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PMID:Role of the NADP/thioredoxin system in the reduction of alpha-amylase and trypsin inhibitor proteins. 187 51

In this study, the interactions among breed of cattle, adipose tissue site and specific incubation conditions were investigated. Subcutaneous and i.m. adipose tissues were obtained from 10 Angus and 9 Santa Gertrudis steers immediately postmortem. Adipose tissue explants were incubated acutely for 2 h immediately at slaughter or after being cultured 48 h with or without 1 mU/ml insulin and 30 mg/ml bovine serum albumin; the incorporation of 14C-labeled acetate and glucose (5 mM, plus 5 mM unlabeled lactate) into lipid fractions was measured. AT the same chronological age, Angus steers had a more youthful lean maturity score, higher USDA marbling score and higher USDA quality grade (P less than .05) than did carcasses from Santa Gertrudis steers. The lower marbling score of the Santa Gertrudis steers was paralleled by smaller i.m. adipocytes (P less than .05) relative to Angus steers. Pentose cycle reductase and NADP-malate dehydrogenase activities were greater in Angus i.m. adipose tissue than in Santa Gertrudis i.m. adipose tissue, which would provide more reducing equivalents (NADPH) and glycerol for fatty acid biosynthesis and triacylglycerol esterification. Correspondingly, Angus i.m. adipose tissue exhibited a greater rate of lipogenesis from acetate and glucose (P less than .05) than did Santa Gertrudis i.m. adipose tissue in acute incubations. The presence of insulin resulted in higher rates of lipogenesis from acetate in Angus s.c. adipose tissue than in Santa Gertrudis s.c. adipose tissue after 48 h of explant culture. These data indicate that i.m. and s.c. adipose tissues exhibit aspects of lipid metabolism unique to each tissue and suggest that breed-related differences in adipose tissues may explain the divergent responses to insulin observed in different laboratories.
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PMID:Lipogenesis in acute and 48-hour cultures of bovine intramuscular and subcutaneous adipose tissue explants. 200 9

The reactivity of human thioredoxin (HTR) was tested in several reactions. HTR was as efficient as E. coli or plant and algal thioredoxins when assayed with E. coli ribonucleotide reductase or for the reduction of insulin. On the other hand, HTR was poorly reduced by NADPH and the E. coli flavoenzyme NADPH thioredoxin reductase as monitored in the DTNB reduction test. When reduced with dithiothreitol (DTT), HTR was much less efficient than thioredoxin m and thioredoxin f, the respective specific thioredoxins for the chloroplast enzymes NADP-malate dehydrogenase (NADP-MDH) and fructose 1,6 bisphosphatase (FBPase). Finally, HTR could be used in the photoactivation of NADP-MDH although less efficiently than thioredoxin m, proving nevertheless that it can be reduced by the iron sulfur enzyme ferredoxin thioredoxin reductase in the presence of photoreduced ferredoxin. Based on sequence comparisons, it was expected that HTR would display a reactivity similar to chloroplast thioredoxin f rather than to thioredoxin m. However the observed behavior of FTR did not exactly fit this prediction. The results are discussed in relation to the structural data available for the proteins.
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PMID:Human thioredoxin reactivity-structure/function relationship. 217 90


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