Chemical-damage MINE: A database of curated and predicted spontaneous metabolic reactions.

Spontaneous reactions between metabolites are often neglected in favor of emphasizing enzyme-catalyzed chemistry because spontaneous reaction rates are assumed to be insignificant under physiological conditions. However, synthetic biology and engineering efforts can raise natural metabolites' levels or introduce unnatural ones, so that previously innocuous or nonexistent spontaneous reactions become an issue. Problems arise when spontaneous reaction rates exceed the capacity of a platform organism to dispose of toxic or chemically active reaction products.

Tracking Polymicrobial Metabolism in Cystic Fibrosis Airways: Metabolism and Physiology Are Influenced by -Derived Metabolites.

Due to a lack of effective immune clearance, the airways of cystic fibrosis patients are colonized by polymicrobial communities. One of the most widespread and destructive opportunistic pathogens is ; however, does not colonize the airways alone. Microbes that are common in the oral cavity, such as , are also present in cystic fibrosis patient sputum and have metabolic capacities different from those of Here we examine the metabolic interactions of and using stable-isotope-assisted metabolomics.

Evidence that the metabolite repair enzyme NAD(P)HX epimerase has a moonlighting function.

NAD(P)H-hydrate epimerase (EC 5.1.99.

Innovations in asthma therapy: is there a role for inhaled statins?

Asthma manifests as chronic airflow obstruction with persistent inflammation and airway hyperresponsiveness. The immunomodulatory and anti-inflammatory properties of the HMG-CoA reductase (HMGCR) inhibitors (a.k.

Discovery of a widespread prokaryotic 5-oxoprolinase that was hiding in plain sight.

5-Oxoproline (OP) is well-known as an enzymatic intermediate in the eukaryotic γ-glutamyl cycle, but it is also an unavoidable damage product formed spontaneously from glutamine and other sources. Eukaryotes metabolize OP via an ATP-dependent 5-oxoprolinase; most prokaryotes lack homologs of this enzyme (and the γ-glutamyl cycle) but are predicted to have some way to dispose of OP if its spontaneous formation is significant. Comparative analysis of prokaryotic genomes showed that the gene encoding pyroglutamyl peptidase, which removes N-terminal OP residues, clusters in diverse genomes with genes specifying homologs of a fungal lactamase (renamed rokaryotic 5-ooprolinase , ) and homologs of allophanate hydrolase subunits (renamed and ).

Pharmacometabolomic signature links simvastatin therapy and insulin resistance.

Introduction: Statins, widely prescribed drugs for treatment of cardiovascular disease, inhibit the biosynthesis of low density lipoprotein cholesterol (LDL-C). Despite providing major benefits, sub populations of patients experience adverse effects, including muscle myopathy and development of type II diabetes mellitus (T2DM) that may result in premature discontinuation of treatment. There are no reliable biomarkers for predicting clinical side effects in vulnerable individuals.

Members of a Novel Kinase Family (DUF1537) Can Recycle Toxic Intermediates into an Essential Metabolite.

DUF1537 is a novel family of kinases identified by comparative genomic approaches. The family is widespread and found in all sequenced plant genomes and 16% of sequenced bacterial genomes. DUF1537 is not a monofunctional family and contains subgroups that can be separated by phylogenetic and genome neighborhood context analyses.

MINEs: open access databases of computationally predicted enzyme promiscuity products for untargeted metabolomics.

Background: In spite of its great promise, metabolomics has proven difficult to execute in an untargeted and generalizable manner. Liquid chromatography-mass spectrometry (LC-MS) has made it possible to gather data on thousands of cellular metabolites. However, matching metabolites to their spectral features continues to be a bottleneck, meaning that much of the collected information remains uninterpreted and that new metabolites are seldom discovered in untargeted studies.

Genomic and experimental evidence for multiple metabolic functions in the RidA/YjgF/YER057c/UK114 (Rid) protein family.

Background: It is now recognized that enzymatic or chemical side-reactions can convert normal metabolites to useless or toxic ones and that a suite of enzymes exists to mitigate such metabolite damage. Examples are the reactive imine/enamine intermediates produced by threonine dehydratase, which damage the pyridoxal 5'-phosphate cofactor of various enzymes causing inactivation. This damage is pre-empted by RidA proteins, which hydrolyze the imines before they do harm.

Arabidopsis and maize RidA proteins preempt reactive enamine/imine damage to branched-chain amino acid biosynthesis in plastids.

RidA (for Reactive Intermediate Deaminase A) proteins are ubiquitous, yet their function in eukaryotes is unclear. It is known that deleting Salmonella enterica ridA causes Ser sensitivity and that S. enterica RidA and its homologs from other organisms hydrolyze the enamine/imine intermediates that Thr dehydratase forms from Ser or Thr.

Plants utilize a highly conserved system for repair of NADH and NADPH hydrates.

NADH and NADPH undergo spontaneous and enzymatic reactions that produce R and S forms of NAD(P)H hydrates [NAD(P)HX], which are not electron donors and inhibit various dehydrogenases. In bacteria, yeast (Saccharomyces cerevisiae), and mammals, these hydrates are repaired by the tandem action of an ADP- or ATP-dependent dehydratase that converts (S)-NAD(P)HX to NAD(P)H and an epimerase that facilitates interconversion of the R and S forms. Plants have homologs of both enzymes, the epimerase homolog being fused to the vitamin B6 salvage enzyme pyridoxine 5'-phosphate oxidase.