one-step-metabolomics-carbohydrates-organic-amino-acids-quantified

One-step Metabolomics: Carbohydrates, Organic and Amino Acids Quantified in a Single Procedure

Every infant born in the US is now screened for up to 42 rare genetic disorders called "inborn errors of metabolism". The screening method is based on ...

Developing Dictyostelium cells form structures containing approximately 20,000 cells. The size regulation mechanism involves a secreted counting factor (CF) repressing cytosolic glucose levels. Glucose or a glucose metabolite affects cell-cell adhesion and motility; these in turn affect whether a group stays together, loses cells, or even breaks up. NADPH-coupled aldehyde reductase reduces a wide variety of aldehydes to the corresponding alcohols, including converting glucose to sorbitol. The levels of this enzyme previously appeared to be regulated by CF. We find that disrupting alrA, the gene encoding aldehyde reductase, results in the loss of alrA mRNA and AlrA protein and a decrease in the ability of cell lysates to reduce both glyceraldehyde and glucose in an NADPH-coupled reaction. Counterintuitively, alrA- cells grow normally and have decreased glucose levels compared with parental cells. The alrA- cells form long unbroken streams and huge groups. Expression of AlrA in alrA- cells causes cells to form normal fruiting bodies, indicating that AlrA affects group size. alrA- cells have normal adhesion but a reduced motility, and computer simulations suggest that this could indeed result in the formation of large groups. alrA- cells secrete low levels of countin and CF50, two components of CF, and this could partially account for why alrA- cells form large groups. alrA- cells are responsive to CF and are partially responsive to recombinant countin and CF50, suggesting that disrupting alrA inhibits but does not completely block the CF signal transduction pathway. Gas chromatography/mass spectroscopy indicates that the concentrations of several metabolites are altered in alrA- cells, suggesting that the Dictyostelium aldehyde reductase affects several metabolic pathways in addition to converting glucose to sorbitol. Together, our data suggest that disrupting alrA affects CF secretion, causes many effects on cellular metabolism, and has a major effect on group size.

Disruption of aldehyde reductase increases group size in dictyostelium.

Eine St&#xF6;rung der Aldehyd-Reduktase erh&#xF6;ht Gruppengr&#xF6;&#xDF;e in Dictyostelium.

Previous studies have given conflicting results as to whether or not folate metabolism is altered in Down syndrome. Folate is necessary to facilitate metabolism of one-carbon units. Folate accepts one-carbon units from one-carbon unit donors, including formiminoglutamate (FIGLU). Folate deficiency leads to accumulation of FIGLU and impairment of one-carbon unit metabolism. FIGLU is a functional measure of folate deficiency.

A folate-dependent metabolite in amniotic fluid from pregnancies with normal or trisomy 21 chromosomes.

Fr&uuml;here Studien haben widerspr&uuml;chliche Ergebnisse, ob Folat-Stoffwechsel im Down-Syndrom ver&auml;ndert ist gegeben. Fols&auml;ure ist zur Erleichterung der Stoffwechsel ein-Kohlenstoff-Einheiten erforderlich. Fols&auml;ure &uuml;bernimmt ein-Kohlenstoff-Einheiten aus einem CO2-Aussto&szlig; Einheit Geber, darunter Formiminoglutamate (FIGLU). Fols&auml;ure-Mangel f&uuml;hrt zu einer Anh&auml;ufung von FIGLU und Wertminderung von einem CO2-Aussto&szlig; Einheit Stoffwechsel. FIGLU ist eine funktionale Ma&szlig; f&uuml;r Fols&auml;ure-Mangel.

Ein Fols&auml;ure-abh&auml;ngigen Metabolit im Fruchtwasser von Schwangerschaften mit Normal oder Trisomie 21 Chromosomen.

Energy restriction increases stress resistance and lifespan in Drosophila melanogaster and other species. The roles of individual nutrients in stress resistance and longevity are largely unknown. The vitamin biotin is a potential candidate for mediating these effects, given its known roles in stress signaling and gene regulation by epigenetic mechanisms, i.e. biotinylation of histones. Here, we tested the hypothesis that prolonged culture of Drosophila on biotin-deficient (BD) medium increases stress resistance and lifespan. Flies were fed a BD diet for multiple generations; controls were fed a biotin-normal diet. In some experiments, a third group of flies was fed a BD diet for 12 generations and then switched to control diets for 2 generations to eliminate potential effects of short-term biotin deficiency. Flies fed a BD diet exhibited a 30% increase in lifespan. This increase was associated with enhanced resistance to the DNA-damaging agent hydroxyurea and heat stress. Also, fertility increased significantly compared with biotin-normal controls. Biotinylation of histones was barely detectable in biotin-deprived flies, suggesting that epigenetic events might have contributed to effects of biotin deprivation.

Feeding Drosophila a biotin-deficient diet for multiple generations increases stress resistance and lifespan and alters gene expression and histone biotinylation patterns.

Energie-Beschr&auml;nkung erh&ouml;ht Stressresistenz und Lebensdauer in Drosophila Melanogaster und andere Arten. Die Rollen der einzelnen N&auml;hrstoffe in Belastbarkeit und Langlebigkeit sind weitgehend unbekannt. Das Vitamin Biotin ist ein m&ouml;glicher Kandidat f&uuml;r die Vermittlung dieser Effekte, seine bekannten Rollen in Stress-Signalisierung und gen-Verordnung von epigenetischen Mechanismen, d.h. Biotinylierung des Histone gegeben. Hier haben wir die Hypothese, die Kultur von Drosophila auf Biotin-Mangel (BD) mittlere erh&ouml;ht Stressresistenz und Lebensdauer verl&auml;ngert getestet. Fliegen waren seit mehreren Generationen eine BD-Di&auml;t gef&uuml;ttert; Steuerelemente wurden eine Biotin-Normal-Di&auml;t gef&uuml;ttert. In vielen Experimenten war eine dritte Gruppe von fliegen eine BD-Di&auml;t f&uuml;r 12 Generationen gef&uuml;ttert und wechselte dann auf Steuerelement-Di&auml;ten f&uuml;r 2 Generationen, m&ouml;gliche Auswirkungen der kurzfristigen Biotin-Mangel zu beseitigen. Fliegt eine BD-Ern&auml;hrung gespeist stellte eine Erh&ouml;hung der Lebensdauer 30 %. Dieser Anstieg war erh&ouml;hte Resistenz gegen die DNA-sch&auml;digenden Agent Hydroxyurea und Hitze Stress zugeordnet. Au&szlig;erdem stieg die Fruchtbarkeit deutlich im Vergleich Biotin-Normal-Steuerelemente. Biotinylierung des Histone war kaum wahrnehmbar in Biotin-beraubt fliegen, was darauf hindeutet, dass epigenetische Ereignisse zu Wirkungen von Biotin Deprivation beigetragen haben k&ouml;nnte.

F&uuml;tterung von Drosophila eine Biotin-Mangel-Ern&auml;hrung f&uuml;r mehrere Generationen erh&ouml;ht die Belastbarkeit und Lebensdauer und ver&auml;ndert Genexpression und Histon Biotinylierung Muster.

Organic acids were examined from normal and Down syndrome pregnancies to identify possible differences between the amniotic fluid from fetuses with Down Syndrome compared with that of normal fetuses.

Organic acid concentrations in amniotic fluid found in normal and Down syndrome pregnancies.

Organische S&auml;uren wurden gepr&uuml;ft von &quot;normal&quot; und Down-Syndrom-Schwangerschaften auf m&ouml;gliche Unterschiede zwischen dem Fruchtwasser von F&ouml;ten mit Down-Syndrom zu erkennen im Vergleich mit der normalen F&ouml;ten.

Organische S&auml;ure Konzentrationen im Fruchtwasser gefunden in Normal und Down-Syndrom-Schwangerschaften.

Some studies of children with Down syndrome have found mild abnormalities in the metabolism of pyridoxine (vitamin B(6)); therefore the present question is whether such abnormalities might also be present in the amniotic fluid of fetuses with Down syndrome.

Pyridoxine-related metabolite concentrations in normal and Down syndrome amniotic fluid.

Einige Studien von Kindern mit Down-Syndrom haben in den Stoffwechsel von Pyridoxin (Vitamin B(6)); milde Anomalien gefunden. Daher ist die vorliegende Frage ob solche Anomalien auch im Fruchtwasser der F&ouml;ten mit Down-Syndrom vorhanden sein k&ouml;nnten.

Pyridoxin-bezogene Stoffwechselprodukt Konzentrationen in Normal und Down-Syndrom-Fruchtwasser.

Diethylene glycol in propofol infusion syndrome?

Diethylenglykol in Propofol-Infusion-Syndrom?

The opportunistic intracellular fungal pathogen Cryptococcus neoformans depends on many antioxidant and denitrosylating proteins and pathways for virulence in the immunocompromised host. These include the glutathione and thioredoxin pathways, thiol peroxidase, cytochrome c peroxidase, and flavohemoglobin denitrosylase. All of these ultimately depend on NADPH for either catalytic activity or maintenance of a reduced, functional form. The need for NADPH during oxidative stress is well established in many systems, but a role in resistance to nitrosative stress has not been as well characterized. In this study we investigated the roles of two sources of NADPH, glucose-6-phosphate dehydrogenase (Zwf1) and NADP(+)-dependent isocitrate dehydrogenase (Idp1), in production of NADPH and resistance to oxidative and nitrosative stress. Deletion of ZWF1 in C. neoformans did not result in an oxidative stress sensitivity phenotype or changes in the amount of NADPH produced during oxidative stress compared to those for the wild type. Deletion of IDP1 resulted in greater sensitivity to nitrosative stress than to oxidative stress. The amount of NADPH increased 2-fold over that in the wild type during nitrosative stress, and yet the idp1Delta strain accumulated more mitochondrial damage than the wild type during nitrosative stress. This is the first report of the importance of Idp1 and NADPH for nitrosative stress resistance.

Isocitrate dehydrogenase is important for nitrosative stress resistance in Cryptococcus neoformans, but oxidative stress resistance is not dependent on glucose-6-phosphate dehydrogenase.

Der opportunistischen intrazellul&auml;re pilzartige Erreger Cryptococcus Neoformans h&auml;ngt davon ab, viele Antioxidantien und Denitrosylating Proteine und Wege f&uuml;r Virulenz im immungeschw&auml;chten Wirt. Dazu geh&ouml;ren die Glutathion und Thioredoxin Bahnen, Thiol-Peroxydase, Cytochrom-C-Peroxidase und Flavohemoglobin Denitrosylase. Alle diese h&auml;ngen NADPH letztlich f&uuml;r katalytische Aktivit&auml;t oder Wartung von einer reduzierten, funktionale Form. Die Notwendigkeit der NADPH bei oxidativen Stress ist in vielen Systemen etabliert, sondern eine Rolle im Widerstand Nitrosative Stress hat nicht auch gepr&auml;gt. In dieser Studie untersuchten wir die Rollen zweier Quellen von NADPH, Glukose-6-phosphat-Dehydrogenase (Zwf1) und NADP (+)-abh&auml;ngige Isocitrate Dehydrogenase (Idp1), in der Produktion von NADPH und Resistenz gegen oxidativen und Nitrosative Stress. Streichung des ZWF1 in C. Neoformans nicht zu einer oxidativen Stress-Empfindlichkeit-Ph&auml;notyp f&uuml;hren oder &Auml;nderungen in der H&ouml;he von NADPH erzeugt w&auml;hrend der oxidativen Stress im Vergleich zu denjenigen f&uuml;r den Wild-Typ. Streichung des IDP1 f&uuml;hrte zu gr&ouml;&szlig;erer Sensibilit&auml;t f&uuml;r Nitrosative Stress als auf oxidativen Stress. NADPH wird mehr 2-fold &uuml;ber, die in den Wildtyp w&auml;hrend Nitrosative stress und noch die idp1Delta Belastung akkumuliert mehr mitochondriale Sch&auml;den als der Wildtyp bei Nitrosative Stress. Dies ist der erste Bericht &uuml;ber die Bedeutung der Idp1 und NADPH f&uuml;r Nitrosative Stressresistenz.

Oxidativer Stress-Resistenz ist nicht abh&auml;ngig von Glucose-6-phosphat-Dehydrogenase Isocitrate Dehydrogenase ist wichtig f&uuml;r Nitrosative Stress-Resistenz bei Cryptococcus Neoformans

The use of long-chain fatty acids (LCFAs) for energy is inhibited in inherited disorders of long-chain fatty acid oxidation (FAO). Increased energy demands during exercise can lead to cardiomyopathy and rhabdomyolysis. Medium-chain triglycerides (MCTs) bypass the block in long-chain FAO and may provide an alternative energy substrate to exercising muscle.

Substrate oxidation and cardiac performance during exercise in disorders of long chain fatty acid oxidation.

Die Verwendung von langkettigen Fetts&auml;uren (Regulationsmechanismus) f&uuml;r Energie wird in Erbkrankheiten der langkettigen Fetts&auml;ure-Oxidation (FAO) gehemmt. Erh&ouml;hten Energiebedarf w&auml;hrend des Trainings k&ouml;nnen zu Kardiomyopathie und Rhabdomyolyse f&uuml;hren. Mittelkettige Triglyceride (MCTs) k&ouml;nnen den Block in langkettigen FAO zu umgehen und eine alternative Energie-Substrat f&uuml;r die Aus&uuml;bung der Muskeln.

Article	Year
Disruption of aldehyde reductase increases group size in dictyostelium. The Journal of biological chemistry\| PubMed ID: 14551196	2004
A folate-dependent metabolite in amniotic fluid from pregnancies with normal or trisomy 21 chromosomes. Fetal diagnosis and therapy\| PubMed ID: 16354994	2006
Feeding Drosophila a biotin-deficient diet for multiple generations increases stress resistance and lifespan and alters gene expression and histone biotinylation patterns. The Journal of nutrition\| PubMed ID: 17709434	2007
Organic acid concentrations in amniotic fluid found in normal and Down syndrome pregnancies. Fetal diagnosis and therapy\| PubMed ID: 18417986	2008
Pyridoxine-related metabolite concentrations in normal and Down syndrome amniotic fluid. Fetal diagnosis and therapy\| PubMed ID: 18417989	2008
Diethylene glycol in propofol infusion syndrome? Drug safety : an international journal of medical toxicology and drug experience\| PubMed ID: 20025084	2010
Isocitrate dehydrogenase is important for nitrosative stress resistance in Cryptococcus neoformans, but oxidative stress resistance is not dependent on glucose-6-phosphate dehydrogenase. Eukaryotic cell\| PubMed ID: 20400467	2010
Substrate oxidation and cardiac performance during exercise in disorders of long chain fatty acid oxidation. Molecular genetics and metabolism\| PubMed ID: 22030098	2012

James D. Shoemaker

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