# Metabolomics/Introduction to Metabolomics/History

Back to Book Table of Contents: Metabolomics Next chapter: Metabolites Go to: Relationship to Traditional Metabolism

## History of Metabolomics
### Ancient China

The beginning of metabolomics traces back all the way to 2000-1500 B.C.when traditional Chinese doctors began using ants in order to evaluate the urine of patients to determine if the urine contained the high glucose of diabetics. At this time, others tasted the urine for sweetness in order to check for the same thing. Urine was also a factor in determining diabetes in Ancient Egypt where it was determined by frequent urination. This earliest use of body fluids to determine a biological condition can be considered the first early uses of metabolomics.

### Galen and Metabolomics

More early steps towards metabolomics came in 300 B.C. when the ancient Greeks first recognized that it was essential to examine body fluids (called humor at the time) in order to predict diseases. From here the next step in the path of Metabolomics was in 131 A.D. when Galen created a system of pathology that combined the humoral theories of Hippocrates with the pythagorean theory. This theory that was formed by Galen was unchallenged and remained standard until the 17th century.

### Metabolomics After the Scientific Revolution

As the 17th century began Santorio Sanctorius became the man who is considered to be the founding father of metabolic studies. In 1614 he published work that he had done on "insensible perspiration" in De Statica Medicina and he determined that the total excretement (urine, feces, sweat) was less than the amount of fluid ingested. His work was the first to obtain physical data and provide quantitative basis of pathology based upon precise studies and instrumentations. The next step in the evolution of metabolomics came in 1674 when Thomas Willis, a physician from England, performed the first analysis of urine and he found that people with diabetes mellitus and diabetes insipidus could be distinguished based solely upon the sweetness of their urine. His research was taken one step further by Matthew Dobson in 1776 by evaluating the urine from diabetics and identifying that there was sugar in the urine of individuals with diabetes.

### The 20th Century

By 1905 J.J. Thomson of the University of Cambridge developed the first mass spectrometer. Also in this year there was more work in determining what other things were in urine and Otto Knut Olof Folin reported that methods for analysis of urine for urea, ammonia, creatine, uric acid. His findings were all published in one issue of Physical Review. The next step in the path to modern Metabolomics came by 1946 when Felix Bloch of Stanford and Edward Purcell of Harvard simultaneously published the first NMR in the same issue of Physical Review. The separation of metabolites through chromatography also made the study of metabolomics possible. As chromatographic separations were discovered and made possible in the 1960's the ability to study individual metabolites was made possible and the technical aspects of the field were made possible.

### Robinson and Pauling

With the necessary instruments in place there was a small gap of time until 1971 when Mamer and Horning performed the first mass-based metabolomic experiments. Shortly after they began their work Modern Metabolomics began to form when Arthur B Robinson and Linus Pauling investigated biological variability being explained by ranges of nutritional requirements. By studying early chromatographic separations in urine he found that the chemical constituents of the urine were loaded with useful information. The first paper on Metabolomics, though not called metabolomics at the time, was by Robinson and Pauling in 1971. It was titled "Quantitative Analysis of Urine Vapor and Breath by Gas-Liquid Partition Chromatography" and was published in Proceedings of the National Academy of Sciences. Robinson went on to publish 19 more papers, and along with colleagues they identified diseases, conditions, and physiological age based on the data that they found. This research was another ground breaking finding, and it led the way for a new discovery in 1990, when hydrophilic interaction chromatography was introduced for the separation of peptides, nucleic acids, and other polar compounds, which was then used in the research of metabolism as well.

### Coining the Term

At this point there was a good basis of what metabolomics would become, but it still was not called metabolomics. In 1998, the term metabolome was introduced by In 1998 the term metabolomics finally came to be when it was used by S.G. Oliver and his colleagues in their published literature in Trends in Biotechnology (its citation is Oliver, S. G., Winson, M. K., Kell, D. B. & Baganz, F. (1998). Systematic functional analysis of the yeast genome. Trends Biotechnol. 16, 373-378).

## The Future of Metabolomics

In the future metabolomics will most likely be based on finding biomarkers in order to determine when disease is present in an individual biological system. Since there is already a use of biological keys to determine disease, such as glucose in urine means diabetes, or high cholesterol being more susceptible to heart disease, so it is clear metabolomics can take advantage of biochemical pathway knowledge. Currently metabolomics is focusing on specializing on 20-100 different metabolites, and although this is just a small portion it is making strides in discovering biomarkers. There is presently a speculation that metabolomics is the key to finding universal biomarkers for diagnosing disease. This has already been begun in experimentation as in the case for biomarkers for reversible myocardial ischemia which can be found through metabolomics, rather than through genomis or proteomics. This is because there is a sign of 60% to 70% rise in citric acid cycle components when there is a restriction of cardiac flow to the heart. These metabolomic changed can be found in the plasma of the blood and that this is a good new biomarker to find signs of somebody suffering from this disease. With some diseases already being diagnosed by these metabolomic biomarkers they could easily become the future of medical detection to diseases.

### The Human Metabalome Project

Less than one per cent of metabolites are measured in clinical tests such as blood and urine analyses, leaving medical professionals without a comprehensive picture of patients' health. The Human Metabolome Project led by Dr. David Wishart of the University of Alberta, Canada completed a first draft of his research on the human metabolome, which consists of 2500 metabolites, 1200 drugs and 3500 food components.The project had started in 2004 with $7.5 million in funding and involved 53 scientists. The first draft was finished on January 23, 2007. The findings have been archived on a freely accessible web resource called the Human Metabolome Database (HMDB). In addition to this work on endogenous metabolites, the group has identified and cataloged nearly 1200 drugs (now archived in DrugBank) and is working to complete a similar database on food additives. The group is using advanced methods in NMR spectroscopy, mass spectrometry, multi-dimensional chromatography and machine learning to facilitate this work.
There are two common components of the present research in metabolomics:
(1) Metabolites are profiled without any bias to any specific group of metabolites
(2) Relationships between metabolites are characterized, currently this is done through multivariate methods.

## Website Sources
### Web Site #1

http://en.wikipedia.org/wiki/Metabolite

#### General Overview

       The purpose of this resource is to give an overview of metabolomics. It goes into the different aspects of metabolomics, including metabolomes, metabolites, metabonomics, history, analytical methods and applications of it. Although this does not go into details it is a great site in order to gain a basic knowledge of the subject matter in order to understand what you are reading when you go into more in depth articles about metabolomics.

#### New Terms
##### Proteomic Analysis

    Large scale study of proteins, particularly their structure and their function. (http://en.wikipedia.org/wiki/Proteomics)

##### Transcriptomic

    Study of the sets of all the messenger RNA (mRNA) molecules that are produced in a population of cells. (http://en.wikipedia.org/wiki/Transcriptomics)

##### Metabolome

    Complete set of small-molecule metabolites found within a biological organism. (http://en.wikipedia.org/wiki/Metabolite)

##### Metabolites

    All the intermediates and products of metabolism. (http://en.wikipedia.org/wiki/Metabolite)

##### Metabonomics

    The quantitative measurement of the dynamic multiparametic metabolic response of a living organism to pathophysiological stimuli or genetic modifications.(http://en.wikipedia.org/wiki/Metabolite)

#### Course Relevance

       This is applicable to our studies in Biochemistry Metabolism in many different ways. As we have studied metabolism in class we went through the different processes of metabolism and looked at all of their metabolic intermediates (Metabolites). The Metabolomics studies the different pathways that a metabolite can go through, which is what we went through in class. A metabolic intermediate of one process can easily feed into another one because they are linked. For example, Glucose-6-Phosphate, is an intermediate in glycolysis, gluconeogenesis, and many other pathways as well. This link between all of the different pathways in the metabolism is what is referred to as metabolomics.

#### Relevance to History

       The process of actually doing metabolomics has been used for hundreds of years but until recently was not a separate entity of science. The separation of metabolites through chromotagrophy is what has made the study of metabolomics possible. As chromotographic separations were discovered and made possible in the 1960's the ability to study individual metabolites was made possible and the technical aspects of the field were made possible. Modern Metabolomics began to form in the 1970's when Arthur Robinson was investigating biological variability being explained by ranges of nutritional requirements. By studying early chromotagraphic separations in urine he found that the chemical constituents of the urine were loaded with useful information. The first paper on Metabolomics, though not called metabolomics at the time, was by Robinson and Pauling in 1971. It was titled "Quantitative Analysis of Urine Vapor and Breath by Gas-Liquid Partition Chromatography" and was published in Proceedings of the National Academy of Sciences. Robinson went on to publish 19 more papers, and along with colleagues they identified diseases, conditions, and physiological age based on the data that they found. It took 20 years for Robinson's research to really catch on and in the 1990's the idea blossomed and the term metabolomics was formed(the first paper to use the term metabolome was in 1998 and its citation is Oliver, S. G., Winson, M. K., Kell, D. B. & Baganz, F. (1998). "Systematic functional analysis of the yeast genome. Trends Biotechnol. 16, 373-378"). Despite the fact that the term began to be used in the 1990's the actual study of metabolomics wasn't actually promoted until 2004 and on January 23, 2007 the Human Metabolome Project, that had been led by Dr. David Wishart of the University of Alberta, Canada completed a first draft of his research on the Human Metabolome, which consists of 2500 metabolites, 1200 drugs and 3500 food components.
There are two common components of the present research in metabolomics:
(1) Metabolites are profiled without any bias to any specific group of metabolites
(2) Relationships between metabolites are characterized, currently this is done through multivariate methods.

### Web Site #2

http://masspec.scripps.edu/metabo_science/timeline.php

#### General Overview

       The general purpose of this web site itself is to explore the Mass Spectrometry of Metablomics. It gives different sections that are links to resources on metabolomic events, readings on metabolomics, data bases of metabolites, and data analysis tools. The main focus on this site is to show how Mass Spectrometry is used in order to analyze metabolomics, and in order to identify metabolites through the use of mass spectrometry.

#### New Terms
##### Mass Spectrometry

    Analytical Method that measures the mass to charge ratio of charged particles. (http://en.wikipedia.org/wiki/Mass_Spectrometry)

#### Course Relevance

       Although this site offers little information in terms of metabolomics in practice and detail, it offers a very clear timeline of metabolomics tracing it throughout history, from where it started to where it is today. The main connection that can be found through this is that it gives a picture as to when certain things that we are studying came into the picture and where they are developing into in order to see what connections will continue to be made as Human Metabolism gains a better understanding.

#### Relevance to History

       The very earliest steps towards metabolomics was in 300 B.C. when the ancient Greeks first recognized that it was essential to examine body fluids (called humor at the time) in order to predict diseases. From here the next step in the path of Metabolomics was in 131 A.D. when Galen created a system of pathology that combined the humoral theories of Hippocrates with the pythagorean theory. This theory that was formed by Galen was unchallenged and remained standard until the 17th century. As the 17th century began Santorio Sanctorius became the man who is considered to be the founding father of metabolic studies. In 1614 he published work that he had done on "insensible perspiration" in De Statica Medicina and he determined that the total excretement (urine, feces, sweat) was less than the amount of fluid ingested. His work was the first to obtain physical data and provide quantitative basis of athology based upon precise studies and instrumentations. The next step in the evolution of Metabolomics came in 1674 when Thomas Willis, a physician from England, performed the first analysis of urine and he found that people with diabetes mellitus and diabetes insipidus could be distinguished between based solely upon the sweetness of their urine. His research was taken one step further by Matthew Dobson in 1776 by evaluating the urine from diabetics and identifying that there was sugar in the urine of individuals with diabetes. By 1905 J.J. Thomson of the University of Cambridge developed the first mass spectrometer. Also in this year there was more work in determining what other things were in urine and Otto Knut Olof Folin reported that methods for analysis of urine for urea, ammonia, creatine, uric acid. His findings were all published in one issue of Physical Review. The next step in the path to modern Metabolomics came by 1946 when Felix Botch of Stanford and Edward Purcell of Harvard simultaneously published the first NMR in the same issue of Physical Review. With the necessary instruments in place there was a small gap of time until 1971 when Mamer and Horning performed the first mass-based metabolomic experiments. Shortly after they began their work Arthur B Robinson and Linus Pauling used chromatographic separation techniques in order to analyze blood and urine Metabolites and they had their groundbreaking work published in Proceedings of the National Academy of Sciences. This research was another ground breaking finding, and it led the way for a new discovery in 1990, when hydrophilic interaction chromatography was introduced for the separation of peptides, nucleic acids, and other polar compounds, which was then used in the research of metabolism as well. At this point there was a good basis of what metabolomics would become,but it still was not called metabolomics. In 1998 the term metabolomics finally came to be when it was used by S.G. Oliver and his colleagues in their published literature in Trends in Biotechnology. The next step came in 2006 when a new approach called "Sniper" metabolomics which uses both chromatography and mass spectrometry in order to analyze metabolites.

### Web Site #3

http://www.drugdiscoverynews.com/index.php?newsarticle=1156

#### General Overview

       This website focuses on metabolomics and how it is paving the way for new opportunities. It talks about how the challenge for metabolomics is to develop techniques that can be used to extract, identify, and quantify all of the samples that are in a biological sample. The main focus of the article is to show that there is a new development that will aid the research of metabolomics and that development is biomarkers. It focuses on the research that is being done in order to find biomarkers in metabolomics in order to better understand the human body.

#### New Terms
##### Biomarkers

    A substance used as an indicator of a biologic state. (http://en.wikipedia.org/wiki/Biomarker)

#### Course Relevance

       This site relates to the course because it talks about how we can use metabolites to identify disease. One example of that that we have learned in class is that in diabetes there is glucose found in the urine because there is no insulin that is used to stimulate glycolysis and fatty acid synthesis so excess glucose accumulates in the blood stream and is excreted in the urine. They also talk about how genetics might show who is predisposed to a disease metabolomics shows the conditions present in the individual which is more important.

#### Relevance to History

       There is a brief mention of history in terms of the fact that the term metabolomics surfaced in journal articles in the year 2000, and makes reference to the fact that there was prior research done in the areas of small molecules in biological systems, yet it is just now being classified as a specific branch of studies. This article focuses more on the future of metabolomics than on the past however. It talks about how metabolomics is important in looking for a biomarker in order to determine when disease is present in an individual biological system. Since there is already a use of biological keys to determine disease, such as glucose in urine means diabetes, or high cholesterol being more susceptible to heart disease, so it is clear the metabolomics can take advantage of biochemical pathway knowledge. Currently metabolomics is focusing on specializing on 20-100 different metabolites, and although this is just a small portion it is making strides in discovering biomarkers. There is presently a speculation that metabolomics is the key to finding universal biomarkers for diagnosing disease.

### Web Site #4

http://www.servier.com/pro/cardiologie/pdfs/kub73ang.asp

#### General Overview

       This is another page that is talking about biomarkers in order to detect for disease. This site gives a specific example of detecting for reversible myocardial ischemia through the use of metabolomics. This article talks about how there is no genomic or proteomic sign of reversible myocardial ischemia, but there is a metabolic change that occurs in this disorder.

#### New Terms
##### Myocardial Ischemia

    A disease characterized by reduced blood flow to the heart due to coronary artery disease. (http://en.wikipedia.org/wiki/Ischaemic_heart_disease)

#### Course Relevance

       This site talks about how there are significant changes in plasma levels of end products of the citric acid cycle. There are also changes in the levels of arginine, succinate, and citrulline, which are caused by changes from aerobic to anaerobic procedures of making energy in the heart with the lack of blood supply.

#### Relevance to History

       This article refers to the fact that there is a better signal of reversible myocardial ischemia through metabolomics than through genomis or proteomics. This is because there is a sign of 60% to 70% rise in citric acid cycle components when there is a restriction of cardiac flow to the heart. These metabolomic changed can be found in the plasma of the blood and that this is a good new biomarker to find signs of somebody suffering from this disease. With some diseases already being diagnosed by these metabolomic biomarkers they could easily become the future of medical detection to diseases.

## Article Sources
### History of Metabolomics

http://www3.interscience.wiley.com/cgi-bin/fulltext/112234343/PDFSTART

#### General Overview

       This article talks about the history of metabolomics and how it dates back as far as the ancient Chinese and the Egyptians.

#### New Terms

       All covered by previous articles

#### Course Relevance

       Again this article talks about how there was the use of urine to diagnose disease dating back to ancient times, and it again touches upon the glucose being present in the urine of a diabetic due to the fact that insulin is not released and there is no trigger to undergo glycolysis and to convert excess glucose into fatty acids so high blood levels lead to glucose being excreted in the urine.

#### Reference to History

       The beginning of metabolomics traces back all the way to 2000-1500 B.C. when traditional Chinese doctors began using ants in order to evaluate the urine of patients to determine if the urine contained the high glucose of diabetics. At this time, others tasted the urine for sweetness in order to check for the same thing. This earliest use of body fluids to determine a biological condition can be considered the first early uses of metabolomics. Urine was also a factor in determining diabetes in Ancient Egypt where it was determined by frequent urination. (No other new information from this article that was not in the other articles.

### The National Centre for Plant and Microbial Metabolomics

http://www.metabolomics.bbsrc.ac.uk/

#### Summary

       The Centre is a leading UK facility for plant and microbial metabolomics research, spawning from a joint venture between Rothamsted Research and the Biotechnology and Biological Research Council (BBSRC). The Centre offers services for comprehensive chemical and informatic analysis of plan and microbial metabolites such as nuclear magnetic resonance (NMR), and mass spectroscopy (MS). One of their main projects is MeT-Ro (Metabolomics at Rothamsted) which aims to establish a critical mass of resources that can be used for the study of plant and microbial metabolomics in the development of a high-throughout metabolite fingerprinting service. Another project of theirs is GARBet, the Genomic Arabidopsis Resource Network. This programme offers metabolite profiling for Arabidopsis thaliana research, at a cost.

#### New Terms
##### Nuclear Magnetic Resonance (NMR)

    NMR spectroscopy uses the magnetic properties some nuclei posses to give information on isomers and molecular conformations. A mixture of biochemical entities produces a certain pattern detected by NMR. This is interpreted for the study of metabonomics. NMR can detect any metabolite containing hydrogen by comparing signals to libraries of reference compounds, or by two-dimensional NMR.

##### Chemometrics

    The application of multivariate statistical, pattern recognition and informatics methods to chemical data

##### Mass Spectroscopy (MS)

    This is a tool used to determine the composition of a sample by measuring the mass-to-charge ratio of ions. The tools breaks a sample into ions, separates the ions with different masses, detects the number of ions of each mass, and collects this data to generate a unique mass spectrum. Mass Spectroscopy can be used to identify unknown compounds, determine isotopic composition of elements in a compound, determine the structure of a compound based on its fragments, determine the amount of a compound in a sample, as well as other applications.

##### Metabolome

    The quantitative complement of all the low molecular weight molecules present in the cells in a particular physiological or developmental state

##### Metabonomics

    Integrated, multicellular, biological systems including communicating extracellular environments. This is in contrast to metabolomics which deals with simple cell systems and mainly metabolite concentrations. (This is the distinction made between the two by the Centre)

##### Metabolite Profiling

    Quantitative of Qualitative determination of a group of related compounds or of members of specific metabolic pathways

##### Metabolic Fingerprinting

    Sample classification by rapid, global analysis, without extensive compound identification

##### Gas Chromatography (GC)

    This technique provides high-resolution compound separations and can be used in conjunction with a flame ionisation detector (GC/FID) or a mass spectrometer (GC/MS). Both detection methods are highly sensitive and able to detect almost any organic compound, regardless of its class or structure. However, many of the metabolites found in plant extracts are too involatile to be analysed directly by GC methods. The compounds have to be converted to less polar, more volatile derivatives before they are applied to the GC column.

#### Course Relevance

       This website, and more specifically the Centre and its goals, gives gravity to our study of metabolic pathways and interactions. As Dr. Craig has stressed, each of these pathways does not exist on its own; they are all interconnected often acting simultaneously within the cell. Just as we have begun to study genomics, proteomics, and transcriptomics; metabolomics is a critical aspect of the drive towards coherent studies. It recognizes that the phenotype of an organism is a collection of all of these aspects. Information gained through metabolomic studies will aid in gene annotation and increase our understanding and application of genomic data.

### Metabolomics on the Norwich Research Park

http://www.metabolomics-nrp.org.uk/metabolomics.html

#### Summary

       This site is designed to promote researchers in the areas of metabolomics, proteomics and genomics to collaborate and communicate ideas and findings so as to create a cross-disciplinary environment. The site encourages metabolic analysis in target compound analysis, metabolic profiling, metabolomics, and metabolic fingerprinting using techniques such as gas chromatography, high performance liquid chromatography, nuclear magnetic resonance, direct injection mass spectrometry, and Fourier transform infrared spectroscopy.

#### New Terms
##### Volatile

    Evaporating readily at normal temperatures and pressures.

##### Chromophore

    A chemical group capable of selective light absorption resulting in the coloration of certain organic compounds.

##### Electrospray ionization

    A technique used in mass spectrometry to produce ions.

##### Chemometrics

    The use of statistics and mathematics for experimental design and analysis of chemical data.

##### Electrophysiology

    The branch of physiology that studies the relationship between electric phenomena and bodily processes.

#### Course Relevance

       This source defines metabolomics as “the quantitative measurement of all low molecular weight metabolites in an organism's cells at a specified time under specific environmental conditions”. The research of each of the labs listed on the site involves just that. This is relevant to what we have learned so far in the course in that we have talked about the analysis of compounds involved in metabolic reactions and how changing quantities of these compounds affect the direction and rate of various metabolic reactions. It also talks about the integration of metabolic pathways. We have mentioned in class the complexity of the intertwining of pathways organisms carry out.

### Metabolomics – A New Exciting Field within the “omics” Sciences

http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1241997&blobtype=pdf

#### Summary

       This editorial discusses how metabolomics is a challenging field of study because it’s often questionable which compounds should be considered metabolites and because the number of metabolites vary based on the method of counting. The goal is to develop a single platform that can quantitatively analyze all metabolites simultaneously. This is difficult to do because physical properties as well as concentrations of compounds vary and the metabolome is dynamic meaning temporal or dietary influences can have major effects. “With all metabolites as our goal, the technological hurdle seems to be the limiting step,” however, with the proper technology metabolomics is a tool that can aid in diagnosis of disease or studying effects of toxicants on phenotype. In order to successfully achieve metabolomics, technology needs to provide high throughput, resolution, reproducibility, and sensitivity. Today, this field of study relies on nuclear magnetic resonance (NMR) or mass spectroscopy coupled to chromatography.

#### New Terms
##### Metabolomics

    “systematic study of unique chemical fingerprints that specific cellular processes leave behind”, global study of all small molecules produced in human body

##### Genomics

    analysis of complete genome in order to understand the function of single genes

##### Transcriptomics

    analysis of gene expression

##### Proteomics

    comprehensive protein analysis including their structure and function and the way they work and interact with each other inside the cell

##### Transcriptome

    set of all messenger RNA (mRNA) molecules or “transcripts” produced in one or a population of cells

##### Proteome

    entire complement of proteins expressed by a genome, cell, tissue, or organism

##### Metabolome

    complete set of small-molecule metabolites found within a biological sample

##### Metabolite

    any substance involved in metabolism either as a product or a necessity, intermediates and products of metabolism (hormones and signaling molecules)

##### Metabolic profiling

    quantitative analytical methods are developed for metabolites in a pathway or for a class of compounds

##### Metabolic fingerprinting

    comparison of patterns or fingerprints of metabolites that change in response to disease or toxin exposure

#### Course Relevance

       The information in this editorial relates to what we’ve studied in this course because it defines the metabolome as a dynamic system. We’ve discussed dynamic steady states in terms of homeostasis as well as in energy terms. These dynamic systems or states are easily influenced by external or environmental factors and thus are constantly changing. The editorial also mentioned that the knowledge of integrated pathways helps interpret data as well as aids in determining how to measure flux (rate of movement) through pathways. Integration has been emphasized in class because we’re learning all these various pathways and amazingly they’re all connected somehow. They will often feed into each other and the end product of one pathway will be the starting point of another (glycolysis and gluconeogesis for example). This integration is important in the field of metabolomics.

### Med Bio World: Metabolomics

http://www.medbioworld.com/postgenomics_blog/?p=9

#### Summary

To provide the general idea into how metabolomics affects many science fields such as biochemistry, analytical chemistry and biology

#### New Terms
##### Proteomics

    the large-scale study of proteins, particularly their structures and functions.

##### Proteome

    the collection of proteins found in a particular cell type under a particular set of environmental conditions such as exposure to hormone stimulation.

##### Biomarkers

    a substance used as an indicator of a biologic state. It is a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.

##### Neurotransmitters

    chemicals that are used to relay, amplify and modulate signals between a neuron and another cell.

##### Sub-threshold

    Not strong enough to be perceived or to produce a response.

#### Course Relevance

       This resource dipped into a lot of chemistry fields. This includes biochemistry and analytical chemistry. This resource correlates some analytical techniques such HPLC (High Performance Liquid Chromatography – using high pressure to pump liquid to force small analytes through a column) and coulometric electrode array detection to analyze redox active compounds. In the previous weeks, we study how redox reactions are important in the bioenergetics aspect of metabolic processes. This includes the concept of dehydrogenases of NAD+ to NADH; important in lactic fermentation in muscles and ethanol fermentation in yeast. In addition, redox reaction is important in the conversion of NADP+ to NADPH to fuel the pentose phosphate pathway from Glucose 6-phosphate to Ribose 5-phosphate to make DNA, RNA and other nucleotides.

### Systematic functional analysis of the yeast genome

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TCW-3TVXPC7-3&_user=47004&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000005018&_version=1&_urlVersion=0&_userid=47004&md5=e361ed6e2e79163ada362703f19c3a4e

#### Summary

This science paper discusses the uses of gene products created by the Saccharomyces cerevisiae genome in the living tissue of the cell. It touches on other entire complimentary systems in a cell, including the transcripteome, proteome, and metabolome. It reviews the many protocols used to acquire the necessary information to complete each of these different yet related systems.

#### Key Terms

transcripteome- set of all mRNA molecules in a given organism.