Table of Contents
Metabolites are organic compounds that are starting materials/intermediates in metabolism pathways. Metabolites are small simple structures absorbed in a diet. They include vitamins and essential amino acids. They can be used to construct more complex molecules, or they can be broken down into simpler ones. Intermediary metabolites may be synthesized from other metabolites and often release chemical energy. For example, glucose, can be synthesized via gluconeogenesis (an anabolic reaction) to form starch or glycogen, and can be broken down during glycolysis (catabolic reaction) to obtain chemical energy. End products of metabolism are excreted from the organism. Urea, for example, is an end product of protein degradation in man. Carbon dioxide is usually thought of as an end product of carbohydrate, protein, and fat degradation in aerobic organisms, although technically, carbon dioxide, as carbonic acid, can also participate in the biosynthesis of some substances, particularly in plants. Catabolism and Anabolism Catabolism: degradative metabolism involving the release of energy and resulting in the breakdown of complex materials (as proteins or lipids) within the organism. Anabolism: the constructive part of metabolism concerned especially with macromolecular synthesis.
Metabolites and their pathways
GenomeNet is a resource database developed by the Kyoto University Bioinformatics Center dedicated to provide computational devices to aid the study on the genome are various areas in biomedical sciences. The database provide tons of diversified maps of various metabolic pathways in humans and in plants. In addition, topics such as disease and drugs research are also mentioned and discussed in details with visual aids. Gene sequencing and analysis are also hugely emphasized at GenomeNet that provides many bioinformatic tools to in studying the genome sequence motif, phylogenetic research, and everything else you want to know about genes. One of the huge contribution from GenomeNet is providing KEGG maps and pathways that served as visual aids for studying of Matabolomics.
Kyoto Encyclopedia of Genes and Genomes or KEGG, is a database of biological systems which consists of genes, proteins, chemical building blocks, molecular pathways, hierarchies and relationships between various biological objects. KEGG links genomes to biological systems and maps pathways together to see the interactive cycle and the metabolites involved. You can also search through the KEGG website by entering a specific organism.
Primary Metabolites: Below are links that show the different pathways of all Primary metabolites. Primary metabolites encompass reactions involving compounds which are formed as part of the normal anabolic and catabolic processes. These processes take in the cells of the organism.
|KEGG Maps of Some Primary Metabolites|
New Vocabulary: 1. Orthologs, or orthologous genes, are genes in different species that are similar to each other because they originated from a common ancestor. 2. Ohnologous genes are paralogous genes that have originated by a process of whole-genome duplication. 3. Paralogs: a gene in an organism that is duplicated to occupy two different positions in the same genome, making the two copies paralogous. 4. Xenologs: Homologs resulting from horizontal gene transfer between two. Xenologs can have different functions, if the new environment is vastly different for the horizontally moving gene. In general, though, xenologs typically have similar function in both organism 5. Gametology: term which denotes the relationship between homologous genes on nonrecombining, opposite sex chromosomes. Gametologs result from the origination of genetic sex determination and barriers to recombination between sex chromosomes
Relevance: This website database relates to our course work and text book by compiling all of the metabolism pathways. It defines metabolites, characterizes them in their role they play in any pathway and gives us a clear view on the relationship it has with organism as a whole. This database can be used for research to further develop our understanding in the world of Metabolomics which will in turn help us understand and maybe even cure different illnesses.
MetaCyc is a database for over 900 primary and secondary metabolic pathways from various organisms; it also contains associated compounds, enzymes, and genes. Similary to KEGG, MetaCryc database aid the studying of Metabolomics by providing visual aid of many metabolic pathways.
The exciting aspect of MetaCyc pathways is the detail explanation of the pathways. You can view all metabolites and their subclasses. (It also allows you to see all metabolites in relationship to each other and their hierarchy.) New vocabulary: 1. Prostaglandin is any member of a group of lipid compounds that are derived enzymatically from fatty acids and have important functions in the animal body. Every prostaglandin contains 20 carbon atoms, including a 5-carbon ring. They are mediators and have a variety of strong physiological effects; although they are technically hormones, they are rarely classified as such. 2. Cyclooxygenases: Prostaglandins are produced following the sequential oxidation of AA, DGLA or EPA by cyclooxygenases (COX-1 and COX-2) and terminal prostaglandin synthesis. 3. Pseudo compound: is not necessarily a physical compound. For example light, or a mis match of DNA base pairs, could be considered pseudo compounds. 4. Superatoms: are clusters of atoms that seem to exhibit some of the properties of elemental atoms. 5. Taxon (plural taxa), or taxonomic unit, is a name designating an organism or group of organisms.
Relevance: This web site database relates to our course work and textbook in the same way the KEGG web page is. MetaCyc however allows for a user friendly specific search based on the organism. It also looks for closely on the genome.
The Human Metabolome Database
Human Metabolome Database is the most complete collection of human metabolite and human metabolism data in the world. It contains records for more than 2180 metabolites. It contains every metabolite and where you can find them (biofluids, tissue etc) it gives the molecular structure, weight and IUPC. The HMDB also contains a collection of experimental metabolite concentration data compiled from hundreds of mass spectra and Nuclear Magnetic resonance metabolomic analyses performed on urine, blood and cerebrospinal fluid samples. The HMDB contains compound description, names and synonyms, structural information, physico-chemical data, reference NMR and MS spectra, biofluid concentrations, disease associations, pathway information, enzyme data, gene sequence data, SNP and mutation data as well as extensive links to images, references and other public databases. Another aspect of the HMDB is Biofluid search which allows you to look at normal and abnormal concentrations of different metabolites for 7 different biofluids.
Universe-review.ca is a link that gives a brief summary on different essential metabolites. It goes through the structure of the molecule and their role in various metabolic pathways. Biosynth Chemistry & Biology is another site with specific information on Lipids. New Vocabulary: 1. CAS registry numbers are unique numerical identifiers for chemical compounds, polymers, biological sequences, mixtures and alloys. They are also referred to as CAS numbers, CAS RNs or CAS #s 2. Biofluid: encompasses any fluid found in the body, HMDB includes: Amniotic Fluid, Bile, Blood, Breast Milk, CSF, Feces, Lymph, Menses, Mucus, Saliva, Sebum, Semen, Sweat, Synovial Fluid, Urine, Vitreous Humour and Vomit. 3. Sebum: oily substances are secreted by Sebaceous glands called sebum and the debris of dead fat-producing cells. 4. Simplified molecular input line entry specification or SMILES: is a specification for unambiguously describing the structure of chemical molecules using short ASCII strings. SMILES strings can be imported by most molecule editors for conversion back into two-dimensional drawings or three-dimensional models of the molecules. 5. American Standard Code for Information Interchange (ASCII), character encoding based on the English alphabet. ASCII codes represent text in computers, communications equipment, and other devices that work with text Relevance: While the past two data base are more specific for metabolite pathways, HMDB focuses on the metabolite composition and chemistry/ chemical interaction. This is relevant because HMDB really breaks down each metabolite to the molecular level. HMDB also allows for purchasing of these compounds.
Summary: The main point of this peer review article is to discuss the glycolysis process, which results in the formation of ATP as the main fuel in the anaerobic eukaryote, Monocercomonoides. Both ATP and Glucose are metabolites that relate directly to glycolysis and would be included in the organism's metabalome. Since anaerobic eukaryotes lack a complete tricarboxylic acid cycle, they can only extract few molecule of ATP per molecule of glucose. This is opposite of human cells, which makes this article important as it discusses alternate versions of enzymes in glycolysis. In anaerobic eukaryotes, enzymes such as pyruvate orthophosphate dikinase and pyrophosphate-fructose 6-phosphate phosphotransferase were examined through horizontal gene transfers from the bacteria in question to other eukaryotes. Horizontal gene transfers are processes in which an organism transfers genetic material to another cell that is not its offspring. Analysis of the glycolytic pathway of Monocercomonoides resulted in identification of both single-gene trees and conserved HGT events that provide evidence for the monophyly of protists known as Ecavata. Shared horizontal gene transfer events between oxymonads and both Giardia and Trichomonas further supported this relationship. This relationship becomes an important resource as it focuses on using glucose metabolites of Monocercomonoides to determine its lineage.
Terms: Horizontal Gene Transfer- process in which an organism transfers genetic material to another cell that is not its offspring Monophyly- a group of organisms that includes an ancestral species and all of its descendants. Oxymonad- a group of flagellated protozoa found exclusively in the intestines of termites and other wood-eating insects. Diplomonads- a group of flagellates, most of which are parasitic. Also classified as Protists. Walking primers-is a sequencing method for sequencing large DNA fragments (between 1,3 and 7 kilobases) that works by dividing long sequences into several consecutive short ones. Phylogenetic analyses- Analysis of the evolutionary connections between traits (for example, sequences) Taxa- Any organism or group of organisms of the same taxonomic rank; for example, members of an order, family, genus, or species.
Relevance: How does this information relate to the information that you have studied in this course to date? This resource is very closely related to our current coursework. As one would recall we had to memorize the complete glycolysis pathway, which is exactly what this article covered. It focused on the enzymes involved in the pathway, which are some that I have memorized. It also reviewed the process through an anaerobic prospective, which sheds light on how glycolysis can be altered but still produce ATP. This is very interesting as we mainly focused on just the one type of glycolysis.
Institute for Analytical Sciences
Summary: ISAS’s main focus is to create analytical methods that will be able to answer questions about a metabolites specificity, selectivity, and dynamic range. They want to be able to identify a metabolom in a single step (ex: from a sample of air breathed out by a person being able to identify dangerous metabolites that would signal cancer was present in the lungs). Another goal of ISAS is to detect differences at the single cell level that come from mutations and the varying environments that each cell is in.
Terms: Biogenic- necessary for the maintenance of life processes (http://www.thefreedictionary.com/biogenic) Mycotoxins-A toxin produced by a fungus. The term is usually reserved for fungal metabolites that are toxic to man and/or animals and are produced by molds growing on foodstuffs (e.g., aflatoxins, ergot alkaloids). (http://www.plantpath.cornell.edu/glossary/Defs_M.htm)
Microfluidics- Microfluidics is the science of designing, manufacturing, and formulating devices and processes that deal with volumes of fluid on the order of nanoliters or picoliters. The devices themselves have dimensions ranging from millimeters down to micrometers. (http://whatis.techtarget.com/definition/0,,sid9_gci526632,00.html)
Hyphal- a long, branching filamentous cell of a fungus, and also of Actinobacteria. In fungi, hyphae are the main mode of vegetative growth, and are collectively called a mycelium. (http://en.wikipedia.org/wiki/Hyphal)
Amperometric- relating to or being a chemical titration in which the measurement of the electric current flowing under an applied potential difference between two electrodes in a solution is used for detecting the end point (http://www.webster.com/dictionary/amperometric)
Voltammetry- is a category of electroanalytical methods used in analytical chemistry and various industrial processes. In voltammetry, information about an analyte is obtained by measuring the current as the potential is varied. (http://en.wikipedia.org/wiki/Voltammetry)
Chronocoulometry- The study of electrode surface properties, such as surface area. (http://www.answers.com/topic/chronocoulometry?cat=technology)
Cytostatic- inhibiting or suppressing cellular growth and multiplication (http://medical-dictionary.thefreedictionary.com/cytostatic)
Relevance: A lot of the techniques that ISAS uses so far are similar to subjects we have studied in the course. ISAS uses nuclear magnetic resonance spectrometry to evaluate intracellular and extracellular metabolites in human bowel tissues in an attempt to identify metabolites created by cancer cells. In Chapter 4 we learned that NMR can show the dynamic part of a components structure (folding, conformational alterations, and interactions with different molecules). Through the use of this method people could diagnosed with colorectal cancer earlier and through a less invasive method than before. Since cancer cells have mutated genes and create different metabolites than the colorectal cells normally would, a method being able to identify these products would be very helpful. In chapter 3 we learned about Mass Spec methods including MALDI MS, ESI MS, and MS/MS. ISAS uses ion mobility mass spectrometry in a lot of their projects including mold identification, analysis of breath to check for diabetes and lung cancer. Ion Mass Spec (IMS) detects low amounts of chemicals by using a homogenous electric field to see differences in migration of the gas phase ions. Where proteomics and genomics can show general drug treatments for problems, the Single Cell Laboratory research could be used to create specific drugs for each individual person’s unique cells and how their metabolome might be different.
1)A metabolome study of the steady-state relation between central metabolism, amino acid biosynthesis and penicillin production in Penicillium chrysogenum 
2)A critique of the molecular target-based drug discovery paradigm based on principles of metabolic control: Advantages of pathway-based discovery 
3)Metabolomics - the way Forward 
Images The following links are images, structures and diagrams of each previously mentioned metabolite. File:Http://www.brynmawr.edu/Acads/Chem/mnerzsto/carb-1.htm - Carbohydrate structures. File:Http://www.ncbi.nlm.nih.gov/sites/entrez?db=pccompound&term=carbohydrate – PubChem images for Carbohydrate. File:Http://www.ncbi.nlm.nih.gov/sites/entrez - PubChem images for Lipids. File:Http://www.chemistryland.com/ElementarySchool/BuildingBlocks/Lipids.jpg - Lipid File:Http://www.ncbi.nlm.nih.gov/sites/entrez - PubChem Amino Acids File:Http://www-jmg.ch.cam.ac.uk/data/molecules/amino/ - All Amino Acids (formula and diagram) File:Http://www.ncbi.nlm.nih.gov/sites/entrez - Nucleotide PubChem File:Http://publications.nigms.nih.gov/thenewgenetics/images/ch1 nucleotide.jpg - The big picture - Nucleotides File:Http://www.nvo.com/jin/nss-folder/scrapbookcell/4 nucleotide.jpg – 4 Nucleotides File:Http://www.ncbi.nlm.nih.gov/sites/entrez - Co-factors PubChem File:Http://www.ncbi.nlm.nih.gov/sites/entrez PubChem Glycan