Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two distinct patterns of activity obtained with the substrates azocasein and azocollagen suggested that Penicillium urticae produces at least two intracellular proteinases during its antibiotic-production phase. Cell extracts fractionated using high resolution gel filtration actually separated three major activities. These three pooled fractions contained predominantly cysteine-type proteinases, as indicated by their sensitivities to inhibitors and by the enhancement of their activities with dithiothreitol and ethylenediamine-tetracetic acid. One of these fractions also appeared to contain significant levels of serine-type proteinases. The three pools could be differentiated from one another by changes in their substrate specificities over a range of pH values, and by their stabilities during storage and at elevated temperatures. Further purification by non-denaturing polyacrylamide gel electrophoresis, revealed that two of the fractions each contained five apparently different activities while in the third pooled fraction, thirteen individual activities were detected. The range of properties displayed by these proteinases is consistent with their probable involvement in general protein degradation, a crucial process which during starvation sustains the supply of substrate necessary for secondary enzyme synthesis as well as contributing to the short lifetime of these same secondary enzymes.
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PMID:An analysis of intracellular proteinases from antibiotic-producing cells of Penicillium urticae. 307 27

Proteinases of the cellular slime mould Dictyostelium discoideum have been analysed using electrophoresis on polyacrylamide gels containing gelatin (gelatin/PAGE). Multiple proteinase forms were apparent in vegetative myxamoebae, but the presence of individual enzyme forms depended on the manner in which the cells were grown. Axenic cells had a characteristic A-pattern of proteinases consisting of six bands, the most active enzymes having apparent Mr values of 51,000 and 45,000 (these have been named ddCP51 and ddCP45, respectively). Some of the proteinases were also present in the medium, the major extracellular form was ddCP42, a 42,000-Mr enzyme. Cells grown in association with bacteria had a distinct B-pattern with three main enzymes that had apparent Mr values of 48,000, 43,000 and 38,000. All of the A- and B-pattern proteinases were most active at acid pH in the presence of dithiothreitol and were inhibited by various agents such as trans-epoxysuccinyl-L-leucylamido-(4-guanidino)butane (E64), leupeptin and chymostatin, which inactivate cysteine proteinases. One of the enzymes, ddCP30, was identified as cysteine proteinase B which had been purified and characterized previously [North, M.J. & Whyte, A. (1984) J. Gen. Microbiol. 130, 123-134]. During starvation of axenic cells in shaken suspensions some of the vegetative proteinases disappeared, ddCP42 was released from the cells and one new enzyme with an apparent Mr of 48,000 appeared. Addition of cyclic AMP had little effect on these changes. When the axenically grown myxamoebae underwent development on filters, similar changes in band pattern were observed and the aggregation stage was characterized by the presence of three cysteine proteinase bands (apparent Mr values of 48,000, 45,000 and 43,000). Proteinases, especially ddCP42, were released from the cells and could be collected from the buffer-saturated pads which supported the filters. The results demonstrate that cysteine proteinases are present throughout growth and development of D. discoideum and that the forms present are subject to nutritional and developmental regulation.
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PMID:Multiple cysteine proteinase forms during the life cycle of Dictyostelium discoideum revealed by electrophoretic analysis. 317 50

Cell growth using homocysteine as a source of cysteine-sulphur requires two enzymes, cystathionine synthase (CS) and gamma-cystathionase (CT). The second of these enzymes, CT, is apparently present in most cell lines regardless of their tissues of origin, since most cells can grow in vitro in the absence of cystine if they are provided with cystathionine, the intermediate in the pathway. Likewise, homocysteine will support the growth of many human cells. However, of a wide range of rodent cells, only well-differentiated rat hepatoma cells were found to grow using homocysteine in place of cystine. It is shown that cell growth in homocysteine-medium correlates well with the presence in the cells of detectable levels of CS. Furthermore, in cells able to grow in homocysteine-medium, it is possible to demonstrate the homocysteine-dependent trans-sulphuration of serine to cysteine. Growth in homocysteine-medium is not dependent on the release of preformed cysteine from disulphide complexes with serum proteins. In cell hybrids, and in 'dedifferentiated' variants of rat hepatomas, CS, but not CT, is subject to extinction coordinately with well-characterized liver-specific traits. For rodent cells, homocysteine-medium thus acts as a selective medium requiring the expression of a single liver-specific trait, CS. In addition it is shown that, in certain hepatoma variants, CS is regulated co-ordinately with a urea-cycle enzyme (carbamoyl phosphate synthetase I) by glucocorticoids and cyclic-AMP. Cell death through cysteine starvation is briefly considered. The immediate cause of death is apparently an insufficient supply of reduced glutathione. Selenium and vitamin E assist cell growth when the supply of cysteine is limiting.
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PMID:Characterization of cystathionine synthase as a selectable, liver-specific trait in rat hepatomas. 379 84

Leukocyte and plasma concentrations of free glutathione, cysteine, methionine, and taurine, and total glutathione and cysteine concentrations were determined in healthy human subjects before and during a seven-day period of total energy deprivation. In leukocytes a progressive decline in total glutathione concentration was found during seven days of starvation due to a decrease in free glutathione content. An increased mixed protein-bound glutathione concentration was calculated, whereas the total cysteine level was unaltered. Fasting resulted in a decreased plasma concentration of free glutathione, whereas the total glutathione level remained unchanged. Free leukocyte concentrations of taurine and methionine were reduced, whereas plasma sulfur amino acid levels were essentially unaffected. These results probably reflect a limited availability of sulfur amino acids during fasting, when glutathione is used as cysteine reservoir for synthesis of other vital sulfur containing compounds. The potential use of leukocyte glutathione, methionine, and taurine concentrations as intracellular indicators of sulfur amino acid deficiency are stressed.
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PMID:The effect of fasting on leukocyte and plasma glutathione and sulfur amino acid concentrations. 394 86

A cysteine-requiring mutant of the parent strain Escherichia coli Hfr Cavalli (RC(rel), Met(-), lambda) has been isolated. The mutant was selected by using replica plating after mutagenesis by N-methyl-N'-nitro-N-nitrosoguanidine. The mutation appears to be in the gene for sulfite reductase, since the mutant could utilize sulfide but not sulfite as a sulfur source. The mutant was found to be RC(rel) with respect to both methionine and cysteine. During cysteine starvation, transfer ribonucleic acid (tRNA) deficient in 4-thiouracil was produced, and in vivo studies indicate that this tRNA can accept sulfur groups to a greater extent than normal tRNA. Further, there were differences both in the rate and extent of amino acid acceptance between normal and sulfur-deficient tRNA. This suggests that thionucleotides are involved in at least one of the biological functions of the tRNA molecule.
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PMID:Sulfur-deficient transfer ribonucleic acid in a cysteine-requiring, "relaxed" mutant of Escherichia coli. 490 13

Wachsman, J. T. (University of Illinois, Urbana), and L. Hogg. Use of thymineless death to enrich for doubly auxotrophic mutants of Bacillus megaterium. J. Bacteriol. 87:1118-1122. 1964.-When strain KM:T(-), a thymine auxotroph of Bacillus megaterium strain KM, is allowed to undergo thymineless death on a minimal medium, the survivors are greatly enriched in polyauxotrophic mutants. Cells were irradiated with ultraviolet light, grown in the presence of thymidine and a complete amino acid mixture, and then starved for thymidine in the absence of amino acids. Doubly auxotrophic mutants (thymine(-) amino acid(-)) may account for more than 90% of the survivors. The most reproducible results were obtained when sucrose (0.4 m) was added to both growth and starvation media. Although the percentage of mutants among the survivors increases with the time of thymine starvation, the absolute number of double auxotrophs per milliliter decreases. It is probable that the extent of cross-feeding determines both the mutant yield and the mutants types. Substrains of KM:T(-) having additional requirements for each of the following amino acids have been isolated: histidine, threonine, tyrosine, tryptophan, arginine, isoleucine, methionine, serine, and cysteine.
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PMID:Use of thymineless death to enrich for doubly auxotrophic mutants of Bacillus megaterium. 495 96

1. Choline O-sulphate is taken up from the growth medium to the same extent by sulphur-deficient and sulphur-sufficient mycelia of Aspergillus nidulans, but hydrolysis of the transported sulphate ester in vivo only occurs in the sulphur-deficient mycelia. 2. Choline sulphatase activity could not be detected in vitro in sulphur-sufficient mycelia of wild-type and sulphur mutants of A. nidulans, but after sulphur starvation all strains showed appreciable activity of this enzyme. 3. Optimum activity of choline sulphatase in an ultrasonically treated preparation of sulphur-deficient mycelia was at pH7.5. The optimum substrate concentration was in excess of 25mm and K(m) was 0.035m. The enzyme was completely inhibited by 10mm-SO(3) (2-), PO(4) (3-), CN(-) and cysteine. 4. Growth of sulphur-deficient mycelia on various sulphur sources resulted in a decrease of choline sulphatase activity in vitro. The decrease appeared to be due to a repression of choline sulphatase synthesis rather than to inhibition of activity. De-repression by growth on a sulphur-deficient medium was prevented by cycloheximide. Unlike the choline sulphatase of bacteria the fungal enzyme did not need to be substrate-induced. 5. By using sulphur mutants the identity of the co-repressor was limited to S(2)O(3) (2-), cysteine-S-sulphonate, cysteine or compounds derived directly from them. Circumstantial evidence suggests that the co-repressor is cysteine. 6. Inhibition of choline sulphatase activity in vivo was demonstrated with cysteine as the sulphur source for growth.
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PMID:Regulation of choline sulphatase synthesis and activity in Aspergillus nidulans. 563 54

Choline-O-sulfate uptake by Penicillium notatum showed the following characteristics. (i) Transport was mediated by a permease which is highly specific for choline-O-sulfate. No significant inhibition of transport was caused by choline, choline-O-phosphate, acetylcholine, ethanolamine-O-phosphate, ethanolamine-O-sulfate, methanesulfonyl choline, 2-aminoethane thiosulfate, or the monomethyl or dimethyl analogues of choline-O-sulfate. Similarly, no significant inhibition was caused by any common sulfur amino acid or inorganic sulfur compound. Mutants lacking the inorganic sulfate permease possessed the choline-O-sulfate permease at wild-type levels. (ii) Choline-O-sulfate transport obeyed saturation kinetics (K(m) = 10(-4) to 3 x 10(-4)m; V(max) = 1 to 6 mumoles per g per min). The kinetics of transport between 10(-9) and 10(-1)m external choline-O-sulfate showed that only one saturable mechanism is present. (iii) Transport was sensitive to 2,4-dinitrophenol, azide, N-ethylmaleimide, p-chloromercuribenzoate, and cyanide. Ouabain, phloridzin, and eserine had no effect. (iv) Transport was pH-dependent with an optimum at pH 6. Variations in the ionic strength of the incubation medium had no effect. (v) Transport was temperature-dependent with a Q(10) of greater than 2 between 3 and 40 C. Transport decreased rapidly above 40 C. (vi) Ethylenediaminetetraacetate (sodium salts, pH 6) had no effect, nor was there any stimulation by metal or nonmetal ions. Cu(++), Ag(+), and Hg(++) were inhibitory. (vii) The initial rate at which the ester is transported was independent of intracellular hydrolysis. After long periods of incubation (> 10 min), a significant proportion of the transported choline-O-sulfate was hydrolyzed intracellulary. In the presence of 5 x 10(-3)m external choline-O-sulfate, the mycelia accumulated choline-O-sulfate to an apparent intracellular concentration of 0.075 m by 3 hr. Transport was unidirectional. No efflux or exchange of (35)S-choline-O-sulfate was observed when preloaded mycelia were suspended in buffer alone or in buffer containing a large excess of unlabeled choline-O-sulfate. (viii) The specific transport activity of the mycelium depended on the sulfur source used for growth. (ix) Sulfur starvation of sulfur-sufficient mycelium resulted in an increase in the specific transport activity of the mycelium. This increase was prevented by cycloheximide, occurred only when a metabolizable carbon source was present, and resulted from an increase in the V(max) of the permease, rather than from a decrease in K(m). The increase could be partially reversed by refeeding the mycelia with unlabeled choline-O-sulfate, sulfide, sulfite, l-homocysteine, l-cysteine, or compounds easily converted to cysteine. The results strongly suggested that the choline-O-sulfate permease is regulated primarily by repression-derepression, but that intracellular choline-O-sulfate and cysteine can act as feedback inhibitors.
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PMID:Specificity and control of choline-O-sulfate transport in filamentous fungi. 572 99

The nucleotide sequence of the yeast gene TRP5 and its 5' and 3' flanking regions was determined. The deduced coding sequence for tryptophan synthase contains 2,127 base pairs. The protein chain has a calculated molecular weight of 76,544. Yeast tryptophan synthase, a bifunctional protein, has a primary structure which corresponds to an Escherichia coli tryptophan synthase alpha chain-beta chain fusion. An NH2-terminal 239 amino acid segment of yeast tryptophan synthase is homologous with E. coli tryptophan synthase alpha subunit, while a distal 389 amino acid residue segment is homologous to the E. coli tryptophan synthase beta chain. This order of segments of the yeast enzyme is the reverse of the chromosomal order characteristic of all prokaryotes that have been examined. The two segments are joined by a connecting region of 28 residues in the yeast enzyme which is not homologous to either the alpha or beta chains of the bacterial enzyme. A portion of the connecting region of yeast tryptophan synthase exhibits nucleotide sequence similarity to the 3' terminus of E. coli trpC and the trpC-trpB intercistronic region. Active site cysteine, histidine, and lysine residues in the beta 2 subunit of E. coli tryptophan synthase are conserved in the yeast enzyme. Also conserved in the yeast enzyme are 6/8 amino acid residues having an important role in maintaining the structure and function of the E. coli tryptophan synthase alpha subunit. S1 nuclease mapping was used to identify three major mRNA transcripts with different 5' termini. Potential T-A-T-A sites for transcription initiation were identified, as well as other sequences that occur frequently in yeast genes. A 5' flanking region of TRP5 was shown by DNA/DNA hybridization to be present in multiple copies in the yeast genome. TRP5 mRNA levels, measured by RNA/DNA hybridization, increased 2- to 7-fold in response to starvation for either tryptophan or histidine, indicating transcriptional regulation.
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PMID:Yeast gene TRP5: structure, function, regulation. 627 87

The inhibitor of the cAMP phosphodiesterase of Dictyostelium discoideum is a cysteine-rich glycoprotein, which binds to the enzyme and inactivates it. When the inhibitor is removed, enzymatic activity is restored. Following translation in vitro of RNA from developing cells and immunoprecipitation with anti-inhibitor serum, newly synthesized inhibitor can be detected by sodium dodecylsulfate/polyacrylamide gel electrophoresis and fluorography. The inhibitor can be labeled using [35S]cysteine but not [35S]methionine, in agreement with the previously determined amino acid composition, and can be detected after cell-free translation only if it has been previously acetylated. Purified native inhibitor blocks immunoprecipitation of the inhibitor polypeptide synthesized in vitro. No inhibitor mRNA was detected in growing cells. Translatable mRNA was present 2 h after the beginning of starvation, reached a maximal level after 3 h, and decreased thereafter. Addition of 1 mM cAMP at the beginning of starvation delayed the appearance of translatable inhibitor mRNA. In the presence of 5 microM adenosine cyclic-3',5'-phosphorothioate, a slowly hydrolyzed cAMP analogue, no translatable mRNA could be detected. Following removal of the analogue, the mRNA appeared within one hour and inhibitor was secreted after another hour.
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PMID:Detection and regulation of the mRNA for the inhibitor of extracellular cAMP phosphodiesterase of Dictyostelium discoideum. 630 86


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