SMPDB: The Small Molecule Pathway Database

Abstract

The Small Molecule Pathway Database (SMPDB) is an interactive, visual database containing more than 350 small-molecule pathways found in humans. More than 2/3 of these pathways (>280) are not found in any other pathway database. SMPDB is designed specifically to support pathway elucidation and pathway discovery in clinical metabolomics, transcriptomics, proteomics and systems biology. SMPDB provides exquisitely detailed, hyperlinked diagrams of human metabolic pathways, metabolic disease pathways, metabolite signaling pathways and drug-action pathways. All SMPDB pathways include information on the relevant organs, organelles, subcellular compartments, protein cofactors, protein locations, metabolite locations, chemical structures and protein quaternary structures. Each small molecule is hyperlinked to detailed descriptions contained in the Human Metabolome Database (HMDB) or DrugBank and each protein or enzyme complex is hyperlinked to UniProt. All SMPDB pathways are accompanied with detailed descriptions, providing an overview of the pathway, condition or processes depicted in each diagram. The database is easily browsed and supports full text searching. Users may query SMPDB with lists of metabolite names, drug names, genes/protein names, SwissProt IDs, GenBank IDs, Affymetrix IDs or Agilent microarray IDs. These queries will produce lists of matching pathways and highlight the matching molecules on each of the pathway diagrams. Gene, metabolite and protein concentration data can also be visualized through SMPDB’s mapping interface. All of SMPDB’s images, image maps, descriptions and tables are downloadable. SMPDB is available at: http://www.smpdb.ca.

Identification of endogenous metabolites in human sperm cells using proton nuclear magnetic resonance (1H-NMR) spectroscopy and gas chromatography-mass spectrometry (GC-MS)

“…The total list of metabolites was also analysed using the bioinformatic tool Metabolites Biological Role (MBRole; http:// csbg.cnb.csic.es/mbrole/) in order to identify over-represented or enriched biological pathways that could be putatively active (p-values < 0.05 were considered significant) (Chagoyen & Pazos, 2011). These pathway results were based on the Small Molecule Pathway Database (SMPDB; http://smpdb.ca) (Frolkis et al, 2010;Jewison et al, 2014). Combined analyses of protein and metabolite data sets were also performed to integrate the human sperm metabolomics data described here with the recently compiled human sperm proteome , in order to investigate significantly represented pathways.…”

Metastatic Melanoma Induced Metabolic Changes in C57BL/6J Mouse Stomach Measured by 1H NMR Spectroscopy

“…Valine, leucine and isoleucine are branched-chain amino acids (BCAAs), and the degradation of these three amino acids leads to the production of acetyl-CoA which is then oxidized via the citric acid cycle (TCA cycle). Substantial amounts of valine, leucine and isoleucine will be generated by protein breakdown under fasting conditions [34]. Elevation of these three amino acids in tumor bearing mice observed in this study may be attributed to enhanced protein breakdown induced by metastatic melanoma in stomach.…”

“…In addition to inter-conversion with alanine, pyruvate also plays a central role in key pathways of energy metabolism. It can either be converted by the pyruvate dehydrogenase complex to produce acetylCoA for fatty acid synthesis, or carboxylated by pyruvate carboxylase in gluconeogenesis to produce oxaloacetate which participates the TCA cycle [34]. Alternatively, through the transformation to serine catalyzed by serine dehydratase/threonine deaminase, pyruvate is associated with the glycine and serine metabolism in which the concentrations of methionine, serine, and glycine are significantly up-regulated in this study due to metastasis of melanoma to gastrointestinal tract.…”

“…For example, glutamate can be generated from alanine or aspartate in combination with 2-Oxoglutarate catalyzed by transaminase, the resulting byproducts (pyruvate and oxaloacetate) of which are key components in glycolysis, gluconeogenesis and the TCA cycle. Glutamate can also be metabolized to glutamine through the action of enzyme glutamine synthetase, which connects the pyruvate metabolism and the pyrimidine metabolism, as well as the purine metabolism [34]. The increased level of glutamate in melanoma group suggests that the above mentioned pathways may have been profoundly disturbed.…”

“…the metabolite keys shown in Table 1 Volume 4 the production of xanthine, an important purine that can alternatively be produced from another notable purine, i.e. hypoxanthine, via the action of xanthine dehydrogenase/oxidase [34]. Significantly increased levels of glutamine and uracil as well as decreased hypoxanthine reflect deviations of the nucleotide pools and perturbed pyrimidine/purine metabolism caused by metastatic melanoma in the stomach, which has been observed in many cancers and has proved to be of central importance in malignant transformation and tumor cell differentiation [44].…”