Phosphopantothenoylcysteine synthase catalyzes the formation of (R)-4'-phospho-N-pantothenoylcysteine from 4'-phosphopantothenate and l-cysteine: this enzyme, involved in the biosynthesis of coenzyme A (CoA), has not previously been identified. Recently it was shown that the NH(2)-terminal domain of the Dfp protein from bacteria catalyzes the next step in CoA biosynthesis, the decarboxylation of (R)-4'-phospho-N-pantothenoylcysteine to form 4'-phosphopantetheine (Kupke, T., Uebele, M., Schmid, D., Jung, G., Blaesse, M., and Steinbacher, S. (2000) J. Biol. Chem. 275, 31838-31846). We have partially purified phosphopantothenoylcysteine decarboxylase from Escherichia coli and demonstrated that the protein encoded by the dfp gene, here renamed coaBC, also has phosphopantothenoylcysteine synthetase activity, using CTP rather than ATP as the activating nucleoside 5'-triphosphate. This discovery completes the identification of all the enzymes involved in the biosynthesis of coenzyme A in bacteria.

Adenosine Triphosphate↗

PubMed2001

AAAS meeting. Stem cells make brain cells.

Explore the source record for details and available documents.

Animals↗

PubMed2001

The biosynthesis of coenzyme A in bacteria.

Coenzyme A (I) and enzyme-bound phosphopantetheine (II) function as acyl carriers and as carbonyl activating groups for Claisen reactions as well as for amide-, ester-, and thioester-forming reactions in the cell. In so doing, these cofactors play a key role in the biosynthesis and breakdown of fatty acids and in the biosynthesis of polyketides and nonribosomal peptides. Coenzyme A is biosynthesized in bacteria in nine steps. The biosynthesis begins with the decarboxylation of aspartate to give beta-alanine. Pantoic acid is formed by the hydroxymethylation of alpha-ketoisovalerate followed by reduction. These intermediates are then condensed to give pantothenic acid. Phosphorylation of pantothenic acid followed by condensation with cysteine and decarboxylation gives 4'-phosphopantetheine. Adenylation and phosphorylation of 4'-phosphopantetheine completes the biosynthesis of coenzyme A. This review will focus on the mechanistic enzymology of coenzyme A biosynthesis in bacteria.

Coenzyme A↗

PubMed2001

Intraindividual variability in cognitive performance in persons with chronic fatigue syndrome.

Studies of cognitive performance among persons with chronic fatigue syndrome (CFS) have yielded inconsistent results. We sought to contribute to findings in this area by examining intraindividual variability as well as level of performance in cognitive functioning. A battery of cognitive measures was administered to 14 CFS patients and 16 healthy individuals on 10 weekly occasions. Analyses comparing the two groups in terms of level of performance defined by latency and accuracy scores revealed that the CFS patients were slower but not less accurate than healthy persons. The CFS group showed greater intraindividual variability (as measured by intraindividual standard deviations and coefficients of variation) than the healthy group, although the results varied by task and time frame. Intraindividual variability was found to be stable across time and correlated across tasks at each testing occasion. Intraindividual variability also uniquely differentiated the groups. The present findings support the proposition that intraindividual variability is a meaningful indicator of cognitive functioning in CFS patients.

Adult↗

PubMed2001

In-vitro activation of complement system by lactic acidosis in newborn and adults.

INTRODUCTION: Complement activation occurs secondary to a variety of external stimuli. Lactic acidosis has been previously shown to activate the complement factors C3a and C5a. In the present investigation we examined the differential effect of lactic acidosis on anaphylatoxin levels in cord and adult blood. Furthermore we aimed to determine if the entire complement cascade could be activated by lactic acidosis. METHODS: Cord and adult blood samples (n = 20 each) were collected and incubated for one hour in either untreated condition or with the addition of lactate in two concentrations (5.5 mmol/l vs. 22 mmol/l). Following incubation, levels of C3a, C5a and sC5b-9, and blood gas parameters were determined. RESULTS: Anaphylatoxin (C3a and C5a) and sC5b-9 levels increased with the addition of lactate in a dose-dependent manner in cord and adult blood (C3a: 1 h, 5.5 mmo/l, 22 mmol/l: 418/498/622 microg/l in cord blood; 1010/1056/1381 microg/l in adult blood, p<0,05; similar results were found for C5a and sC5b-9). CONCLUSION: Lactic acidosis leads to an activation of the entire complement system in neonates and in adults. This activation is dose-dependent and more pronounced in adults as compared to neonates.

Acidosis, Lactic↗

PubMed2001

[Polymorphism of the methylenetetrahydrofolate reductase gene (MTHFR) and incidence of hyperhomocysteinemia-related diseases].

Methylenetetrahydrofolate reductase (MTHFR), is a cytosolic enzyme, the product of which is N5-metyltetrahydrofolate, the main form of folates in tissues and the carbon donor for methylation of homocysteine to methionine. In MTHFR gene a series of the pathogenic mutations is known which lead to loss of enzymatic activity as well as the two polymorphic alleles (MTHFR 677T and 1298C) with products displaying the lowered enzyme activity resulting in hyperhomocysteinaemia. These polymorphic alleles of MTHFR represent the main genetic factor contributing to hyperhomocysteinaemia. The better known allele MTHFR 677T is found in different populations with frequency between ca. 0.1 and 0.36. In persons inheriting the variant alleles of MTHFR the increase in the level of homocysteine is noted resulting in the increased susceptibility to vascular diseases and the neural tube defects in the progeny. The procedure recommended for the prevention of effects of deficiency of MTHFR activity consists of the supplementation of the diet with 0.4 mg of folic acid daily.

Folic Acid↗

PubMed2001

WMS-III performance in patients with temporal lobe epilepsy: group differences and individual classification.

The utility of the WMS-III in detecting lateralized impairment was examined in a large sample of patients with temporal lobe epilepsy. Methods of analysis included evaluation of group means on the various indexes and subtest scores, the use of ROC curves, and an examination of Auditory-Visual Index discrepancy scores. In addition, performance on immediate and delayed indexes in the auditory and the visual modality was compared within each group. Of the WMS-III scores, the Auditory-Visual Delayed Index difference score appeared most sensitive to side of temporal dysfunction, although patient classification rates were not within an acceptable range to have clinical utility. The ability to predict laterality based on statistically significant index score differences was particularly weak for those with left temporal dysfunction. The use of unusually large discrepancies led to improved prediction, however, the rarity of such scores in this population limits their usefulness. Although the utility of the WMS-III in detecting laterality may be limited in preoperative cases, the WMS-III may still hold considerable promise as a measure of memory in documenting baseline performance and in detecting those that may be at risk following surgery.

Adult↗

PubMed2001

Low activity of the ahr gene in the ahr dd C57BL congenic mice does not prevent the depression of birth rates observed as result of cigarette smoke exposure.

The ahr gene product is a ligand-activated transcription factor which regulates the expression of a number of enzymes involved in the metabolism of aryl hydrocarbons and mediates the effects of dioxins on tumour promotion. We have assessed the cigarette smoke induced depression of the reproductive capacities in the ahr dd C57BL congenic mice and its crosses with C57BL ahr bb mice. The in vivo exposure of animals to toxic concentrations of cigarette smoke during the period of pairing and the early pregnancy was shown by us to affect the reproduction. The transmission of the ahr b and ahr d alleles was assessed by genotyping the STR polymorphism at D12Mit2 locus linked with the ahr gene. Following the exposure to cigarette smoke the changes in the reproductive capacity of the studied mice have been assessed in relation to the presence of the ahr d allele by measurements of the changes in the rates of conceptions, abortions, births and the number of newborns per female after pairings differing in ahr gene alleles and in the expected ahr d allele frequencies in the progeny. The results indicates that the low activity ahr d allele may decrease the abortive effects of cigarette smoke exposure, but does not confer resistance to the depression of births rates following this exposure.

Abortion, Spontaneous↗

PubMed2000

Microbiology. Fighting bacterial fire with bacterial fire.

Work presented last week at the annual meeting of the American Society for Cell Biology in San Francisco suggests that applying a harmless bacterium or its products to surgical wounds may thwart infections by the dangerous pathogen Staphylococcus aureus, a major cause of hospital-acquired infections. Although physicians have previously pitted one bacterium against another to prevent infections of the intestinal and genitourinary tracts, this is the first attempt to use a friendly microbe to prevent infection of surgical wounds, say experts. The findings also point to a possible mechanism for this "bacterial interference." They suggest that a protein secreted by the harmless bacterium prevents the pathogen from getting a foothold in injured tissue.

Animals↗

PubMed2000

Microbiology. Simple hosts may help reveal how bacteria infect cells.

Important human pathogens invade and harm simple organisms. What's more, these infections require many of the same bacterial genes needed to make mammals sick. These observations suggest that even though simple organisms aren't perfect models for complex hosts such as mammals, the basic mechanisms by which bacteria establish infections in the various organisms may be similar. As a result, the work may help microbiologists identify the host proteins involved in infections, thereby providing potential new targets for antibacterial drugs.

Animals↗

PubMed2000

Academic research. California sets up three new institutes.

Three University of California campuses were chosen last week as sites for a new $900 million program designed to keep the state a world leader in research and to bolster its economy. Each of the three schools will receive $25 million a year for 4 years from the state, with companies and other sources putting up at least twice that amount.

Academies and Institutes↗

PubMed2000

Molecular biology. New way found to study closely related proteins.

Rather than designing specific inhibitors for closely related proteins, researchers are remodeling the proteins to make them uniquely susceptible to inhibition. As described in the 21 September issue of Nature, the technique involves enlarging the active site of an enzyme so that it can bind an inhibitor that won't fit into the active sites of related--but unaltered--enzymes. Researchers can then insert the gene that encodes the modified enzyme into cells or living animals and turn off that enzyme by feeding them the inhibitor--without affecting other, very similar, enzymes. The technique may have some advantages over other approaches to studying the functions of individual proteins, such as mutating or knocking out the genes that encode them, which may disrupt embryonic development, producing abnormal animals or no animals at all.

Amino Acid Substitution↗

PubMed2000

Molecular biology. Targeting intron insertion into DNA.

In work reported on page 452, researchers have found a way to coax certain introns, bits of genetic debris that litter the DNA and interrupt the coding sequences of many genes, to hop into the exact sequences where the researchers want them. The method could enhance all sorts of genetic manipulations, from studying basic gene function to combating viral infections to delivering genes for gene therapy.

Cells, Cultured↗

PubMed2000

American Society for Microbiology. Microbes display their versatility at ASM meeting.

About 12,000 scientists gathered here from 21 to 25 May for the 100th annual meeting of the American Society for Microbiology. This year's lineup boasted presentations on a wide array of topics--everything from the body's defenses against microbial pathogens to bacterial involvement in geological processes.

Animals↗