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Guanosine Monophosphate (GMP)

Guanosine monophosphate structure

Researchers have utilized chemical proteomics in order to identify the novel target molecules of cyclic guanosine monophosphate (cGMP), with the intention of obtaining a better understanding of the cGMP pathway. Experiments were conducted on cGMP that had been immobilized onto agarose beads with linkers directed at three different cGMP positions. The employment of agarose beads allowed for maximum accessibility of cGMP to its binding partners. Using a pull-down assay with the beads as bait on tissue lysates, nine proteins were identified via Matrix-Assisted Laser Desorption/Ionization Time-of-Flight (MALDI-TOF) mass spectrometry. A portion of these proteins consisted of previously identified cGMP targets, which included cGMP-dependent protein kinase and cGMP-stimulated phosphodiesterase. Evidence from competition binding assays determined that protein interactions occurred by specific binding of cGMP into the binding pockets of its target proteins, and were also highly stereo-specific to cGMP against other nucleotides. MAPK1 was confirmed as one of the identified target proteins via immunoblotting with an anti-MAPK1 antibody. Further evidence was provided by observing the stimulation of mitogen-activated protein kinase 1 signaling by membrane-permeable cGMP, in the treated cells. Further research in the field of proteomics is expected to yield more efficient tools and techniques applicable to the identification and analysis of bioactive molecules and their target proteins.

cGMP binding protein isolation revealed that the brain tissue samples had a higher concentration of cGMP binding proteins than did the heart or liver tissue samples. This observation implied that there is a more diverse cGMP signal transduction role in the brain than in the heart or liver. In addition, an increase of MAPK phosphorylation was discovered via immunoblotting with an anti-phospho MAPK antibody. Researchers have determined that direct interactions occur between cGMP binding proteins and cGMP. The binding proteins are also strongly believed to be regulated by the concentration of cellular cGMP. Further research in the field of proteomics is expected to yield more efficient tools and techniques applicable to the identification and analysis of bioactive molecules and their target proteins.


Web Resources:

Resource #1: Nucleotide Metabolism

Main Focus: This resource provides a very comprehensive overview of multiple aspects of nucleotide metabolism. These include biosynthesis, catabolism, salvage pathways, and regulation as well as clinical significance of both purine and pyrimidine nucleotides. Regulation of deoxyribonucleotides (dNTP’s) and interconversion of nucleotides are also discussed. An advantage to this website is that mechanisms are displayed pictorially to make it easier to follow and understand the movement of electrons, bonds, charge, molecules and substituents in these complicated pathways.

New Terms: Endonucleases = degrade DNA and RNA at internal sites producing oligonucleotides Phosphodiesterases = digest oligonucleotides from the ends inward yielding free nucleosides Nucleoside phosphorylases = hydrolyze bases from nucleosides yielding ribose 1- phosphate and free bases PRPP synthetase = requires energy in the form of ATP to generate PRPP (5-phospho--D-ribosyl-1-pyrophosphate), an activated sugar PRPP = 5-phospho--D-ribosyl-1-pyrophosphate, activated sugar Inosine 5’-monophosphate (IMP) = first fully formed purine nucleotide Hypoxanthine = purine base Feedback inhibition = inhibition of an allosteric enzyme at the beginning of a metabolic sequence by the end product of the sequence Purine nucleotide cycle = synthesis of AMP from IMP and salvage of IMP via AMP catabolism causes deamination of aspartate to fumarate Tetrahydrofolate (THF) = carries formyl moieties in the form of N10-formyl-THF Uric acid = product of catabolism of purine nucleotides, insolube substance, excreted in urine as sodium urate crystals Salvage pathway = series of steps in which nucleotides are synthesized from purine bases and nucleosides Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) = enzyme involved in purine metabolism, more specifically the salvage pathway for hypoxanthine and guanine Ribonucleotide reductase = catalyzes conversion of ribonucleotides to deoxyribonucleotides (dNTP’s) von Gierke’s disease = glycogen storage disease I, basic defect in glucose 6-phosphatase, excessive uric acid production Carbamoyl phosphate = rids body of excess nitrogen in pyrimidine synthesis and urea cycle CTP synthase = aminates UTP to form CTP Aspartate transcarbamoylase (ATCase) = rate limiting enzyme of pyrimidine nucleotide biosynthesis Suicide substrates = class of molecules used to inhibit thymidylate synthase, irreversibly inhibit the enzyme(includes 5-fluorouracil and 5-fluorodeoxyuridine) 5-fluorodeoxyuridylate (FdUMP) = drug metabolite, which inhibits thymidylate synthase Anaplerotic reaction = an enzyme-catalyzed reaction that can replenish the supply of intermediates in the citric acid cycle Thioredoxin reductase = enzyme which reduces thioredoxin Glutathione reductase = enzyme which reduces glutathione disulfide (GSSG) to the sulfhydryl form (GSH)

Connections: When analyzing the mechanism for purine nucleotide biosynthesis, there are many common metabolic features present, which we’ve discussed throughout the quarter. Purine nucleotides are built upon a sugar. In the first step, catalyzed by glutamine-PRPP amidotransferase, glutamine acts as a source of ammonia and PPi (inorganic pyrophosphate) is released. The release of this PPi can lead to its cleavage to form two inorganic phosphates. The cleavage of this phosphoanhydride bond provides energy to drive reactions forward. In the steps two, four and five, ATP, an activated molecule is used for energy. In the third and ninth step, tetrahydrofolate, a cofactor, acts to perform 1-carbon transfers at intermediate oxidation levels. Glutamine is used again in the fourth step as a source of ammonia. Step six is a carboxylation reaction, and it’s very unusual that the cofactor biotin is not utilized. Most other carboxylation reactions are biotin dependent. The fumarate produced in step eight can be used to replenish citric acid cycle intermediates, meaning that purine nucleotide synthesis acts as an anaplerotic reaction.

Resource #2: Targets of Natural Compounds Vs. Targets of Chemotherapy Drugs

Main Focus: Cancer cells that receive a high throughput of proliferation signals keep dividing uncontrollably, but if not bombarded with these signals will enter apoptosis. This resource discusses the differences between what natural compounds target and what chemotherapy drugs target in order to reduce the flow of information to a cell leading to cell proliferation, in order to prevent cancer. For the most part, chemotherapy drugs target DNA and more specifically the structure of nucleotides and the integrity of them within DNA as well as enzymes that participate in the synthesis phase such as DNA polymerase and topoisomerase in order to prevent completion of the cell cycle. One way of inhibiting cancer cell proliferation is to inhibit the production of nucleotides. This is done by chemotherapy drugs. For example, methotrexate is a drug that inhibits folate activity, while folate is required for the synthesis of some bases. Another drug is called cytarabine and it inhibits DNA polymerase by substituting the sugar arabinose for ribose during DNA synthesis. This is effective because nucleotides are only functional if they contain ribose. Other chemotherapy drugs such as cyclophosphamide and mitomycin alter the nucleotides within DNA, damaging the DNA and inhibiting its replication and transcription. Intercalating drugs such as bleomycin insert themselves into the DNA between adjacent base pairs causing free radical damage.

New Terms: Proliferation = rapid growth or production of cells through multiplication of parts Apoptosis = form of programmed cell death Cancer = disease in which cells grow and divide aggressively without limits Chemotherapy = treatment of disease by chemicals that kill cells Antimetabolites = chemicals with a similar structure to the chemical required to carry out normal biochemical reactions, interferes with DNA production and cell division, chemotherapy drugs Folate = B vitamin, required for synthesis of some bases Methotrexate = chemotherapy drug which inhibits folate activity Topoisomerase = enzyme which unwinds DNA so DNA replication and gene transcription can take place

Connections: In lecture, we learned how chemotherapeutic agents act by inhibiting enzymes in the nucleotide biosynthesis pathway because cancer cells have a greater requirement for nucleotides as DNA precursors. Glutamine analogs such as azaserine and acivicin inhibit glutamine amidotransferase, making it impossible for glutamine to act as a nitrogen donor. We discussed how thymidylate synthase and dihydrofolate reductase were good targets for chemotherapeutic agents and are inhibited by fluorouracil and methotrexate respectively. Although cancer cells grow fast, they’re weak and if distressed can be defeated.

Resource #3: Purine and Pyrimidine Metabolism Disorders

Main Focus: Under normal conditions, nucleotides act as components of cellular energy systems, signaling, and DNA and RNA production. However, when an enzyme has a defect causing it to malfunction leading to accumulation of compounds in blood, urine, or tissues, this can result in diseased states which can severely affect people and their everyday lives. This resource discusses several disorders of nucleotide metabolism; including disorders of purine salvage, purine nucleotide synthesis, purine catabolism, and pyrimidine metabolism. Not only is the nature of several deficiencies discussed, but diagnosis as well as possible treatment and diet adjustments are mentioned. Lesch-Nyhan syndrome is a disorder of purine salvage and results from a deficiency in the hypoxanthine-guanine phosphoribosyl transferase (HPRT) enzyme which normally aids in salvage pathway for hypoxanthine and guanine leading to uric acid overproduction. Adenosine deaminase deficiency is a disorder of purine catabolism, which results in accumulation of adenosine due to inability of enzyme to convert adenosine and deoxyadenosine to inosine and deoxyinosine. High levels of adenosine causes an increase in levels of ATP and dATP, and the latter inhibits ribonucleotide reductase causing underproduction of the other deoxribunucleotides compromising DNA replication. Immune cells are sensitive to this and this deficiency causes Severe Combined Immunodeficiency. This can be treated by stem cell transplantation and enzyme replacement. Xanthine oxidase deficiency is also a disorder of purine catabolism in which there is a buildup of xanthine due to the incapability of the enzyme to produce uric acid from xanthine and hypoxanthine. This deficiency causes painful xanthine stones and blood in urine.

New Terms: Lesch – Nyhan syndrome = x-linked recessive disorder caused by deficiency of hypoxanthine-guanine phosphoribosyl transferase (HPRT) Hypoxanthine-guanine phosphoribosyl transferase = enzyme involved in purine metabolism, more specifically the salvage pathway for hypoxanthine and guanine Hyperuricemia = presence of high levels of uric acid in the blood Gout = disease caused by deposits of uric acid crystals in the cartilage and tendons leading to inflammation and excruciating pain Allopurinol = xanthine oxidase inhibitor, prevents conversion of hypoxanthine to uric acid, can also prevent oxidation of adenine Adenine phosphoribosyltransferase deficiency = rare autosomal recessive disorder, results in inability to salvage adenine for purine synthesis Phosphoribosylpyrophosphate synthetase superactivity = x-linked recessive disorder, causes purine overproduction Adenylosuccinase deficiency = autosomal recessive disorder, causes mental retardation, autistic behavior, and seizures Myoadenylate deaminase deficiency = inability for the enzyme to convert AMP to inosine and ammonia Myalgia = muscle pain Adenosine deaminase deficiency = inability of enzyme to convert adenosine and deoxyadenosine to inosine and deoxyinosine Purine nucleoside phosphorylase deficiency = rare, autosomal recessive deficiency, immunodeficiency with severe T-cell dysfunction and neurologic symptoms Xanthine oxidase deficiency = inability of enzyme to produce uric acid from xanthine and hypoxanthine leading to precipitation of xanthine in the urine Uridine monophosphate synthase deficiency = causes accumulation of orotic acid

Connections: In class we’ve emphasized the importance of regulation of metabolic pathways and how if there is a disruption or defect in this regulation it can lead to diseased states. Often times enzymes can have or acquire mutations, which prevent them from performing properly. This often leads to accumulation of intermediates in blood or urine, which can lead to diseases. We briefly discussed phenylketonuria (PKU) in class, a genetic defect of amino acid metabolism in which there is a defect in the enzyme phenylalanine hydroxylase (involved in first step of catabolic pathway for phenylalanine). Under normal conditions, the enzyme would convert phenylalanine to tyrosine, but the genetic defect results in accumulation of phenylalanine. PKU can be detected at infancy and impairs normal development of brain causing severe mental retardation. Alkaptonuria (AKU) is also an inheritable disease of phenylalanine catabolism. The defective enzyme is homogentisate 1,2-dioxygenase, normally it would convert homogentisate to maleyloacetoacetate, but the diseased state leads to accumulation of homogentisate which is excreted in urine and turns black upon oxidation. These examples of a lack of regulation caused by enzyme defects in amino acid metabolism are very similar to those of nucleotide metabolism mentioned in this resource. For instance, Lesch-Nyhan syndrome involves accumulation of uric acid in blood due to a defective enzyme, adenosine deaminase deficiency involves accumulation of adenosine and compromise of DNA replication due to a defective enzyme, and xanthine oxidase deficiency involves precipitation of xanthine in urine causing stones due to a defective enzyme. In class, we also discussed various ways in which enzyme activity can be altered and these include allosteric regulation, association with a regulatory protein, sequestration or compartmentation, or covalent modification such as phosphorylation.

Peer-Reviewed Free Full Text Articles:

Article #1: Enhanced Activity of the Purine Nucleotide Cycle of the Exercising Muscle in Patients with Hyperthyroidism

Main Focus: This article discusses a study in which the purine nucleotide cycle is examined as a possible mechanism for causing muscular weakness in patients with hyperthyroidism. A semiischemic forearm exercise test was performed in order to measure metabolites related to the purine nucleotide cycle, ammonia and hypoxanthine, and metabolites of glycolysis, lactate and pyruvate. The levels of the previously mentioned metabolites were measure in the blood at rest, immediately after exercise, and 10 minutes later for four different groups. The four groups examined were; healthy volunteers (control group), patients with untreated thyrotoxic Graves’ disease (untreated group), patients with Graves’ disease treated with methimazole (treated group), and patients in remission (remission group). This study found that lactate and pyruvate levels were elevated in patients with hyperthyroidism after exercise indicating that muscle ATP content decreases, enhancing glycolysis and glycogenolysis. Hypoxanthine and ammonia levels were elevated in patients with hyperthyroidism after exercise, indicating acceleration of the purine nucleotide cycle in hyperthyroidism patients. Hypoxanthine levels were only slightly elevated in patients with hyperthyroidism in comparison to healthy controls and the hypoxanthine production didn’t parallel that of ammonia, which it should have, but the article suggests multiple possibilites to explain this. This study provides evidence of accelerated glycolysis and purine nucleotide catabolism, performed by purine nucleotide cycle, in hyperthyroidism.

New Terms: Myopathy = neuromuscular disease, muscle fibers don’t function resulting in muscular weakness Hyperthyroidism = overactive thyroid gland, result of excessive thyroid hormone production Grave’s disease = thyroid disorder caused by antibody mediated auto-immune reaction Deamination = removal of amine group Semiischemic forearm exercise test = induction of a rapid decrease in ATP content of muscle, stimulating the purine nucleotide cycle Muscle hypotonia = condition of low muscle tone Amyotrophy = progressive wasting of muscle tissue Thyrotoxicosis = condition resulting from excessive concentrations of thyroid hormones in the body Glycolysis = catabolic pathway by which a molecule of glucose is broken down into two molecules of pyruvate Glycogenolysis = catabolism of glycogen by removing glucose monomers Hypokalemia = low concentration of potassium in blood Hypophosphatemia = abnormally low level of phosphate in blood due to electrolyte imbalance

Connections: This article emphasizes ATP balance in skeletal muscles and how the purine nucleotide cycle contributes to this. During exercise, glycogen is consumed and ATP consumption by skeletal muscles increases to a rate faster than that of ATP synthesis. This is when the nucleotide cycle comes in and tries to replenish the insufficient ATP supply. In class we’ve discussed how organisms have regulatory mechanisms that allow them to maintain homeostasis, a steady state. Keeping a constant supply and concentration of ATP can aid in maintaining homeostasis. Reactions are often controlled by the ATP:ADP ratio. Many reactions involve ATP, therefore, if the concentration of ATP were to dramatically drop, many pathways and reactions in our bodies, which act to keep us alive, would not be capable of being carried out and our cells would most likely die. It seems that the same concept can be applied to the purine nucleotide cycle and how it tries to achieve energy balance in the muscles. It was even suggested in the article that the acceleration of purine catabolism in hyperthyroidism is a regulatory mechanism set in place to avoid rapid collapse of ATP balance.

Article #2: Hypoxanthine-guanine phosophoribosyltransferase (HPRT) deficiency: Lesch-Nyhan syndrome

Main Focus: Lesch-Nyhan syndrome is an inborn error of metabolism and is due to complete deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity. This review article provides detailed descriptions of the nature of this disease, common symptoms (including motor disorder, cognitive impairment, and compulsive self-injurious behavior), classification with basis of severity of neurological manifestations and enzyme defect, mechanisms that contribute to the uric acid overproduction caused by the enzyme deficiency, methods for diagnosing patients as well as treatment and prognosis of the disease. The most pertinent of these topics are the mechanisms that contribute to this disease. The deficiency in the HPRT enzyme is the root cause of the uric acid overproduction in children diagnosed with Lesch-Nyhan syndrome and there are multiple mechanisms to explain this. Hypoxanthine and guanine are purine bases from which inosine monophosphate (IMP) and guanosine monophosphate (GMP) are synthesized respectively in the salvage pathway catalyzed by HPRT. A co-substrate, 5’-phosphoribosyl-1-pyrophosphate, (PRPP) is utilized in the reaction. The inherited defect in the HPRT enzyme leads to accumulation of hypoxanthine and guanine. These two purine bases are converted to uric acid in a reaction catalyzed by xanthine oxidase. Since the PRPP co-substrate is not needed in the salvage pathway, it’s available for PRPP amidotransferase, an enzyme which is part of the de novo synthesis of purine nucleotides. Consequently, purine synthesis increases, but since the feedback inhibitors of the de novo synthesis pathway, IMP and GMP, aren’t being synthesized, this pathway runs unregulated resulting in an increase of purine nucleotides.

New Terms: Hypoxanthine-guanine phosphoribosyl transferase = enzyme involved in purine metabolism, more specifically the salvage pathway for hypoxanthine and guanine Lesch – Nyhan syndrome = x-linked recessive disorder caused by deficiency of hypoxanthine-guanine phosphoribosyl transferase (HPRT) Dystonia = abnormal tone of any tissue caused by prolonged repetitive muscle contractions Choreoathetosis = nervous disturbance marked by involuntary and uncontrollable movement of body Ballismus = condition involving twisting, shaking, and jerking motions Aetiology = study of causes or origins Feedback Inhibition = inhibition of an allosteric enzyme at the beginning of a metabolic sequence by the end product of the sequence Amniocentesis = surgical procedure to obtain amniotic cells in order to perform tests in order to detect genetic abnormalities Allopurinol = xanthine oxidase inhibitor that blocks conversion of xanthine and hypoxanthine into uric acid Xanthine lithiasis = accumulation of xanthine stones in body due to administration of too high of a dose of allopurinol Benzodiazepine = family of minor tranquilizers that act against anxiety and convulsions and produce muscle relaxation and sedation Baclofen = used as a reactant of skeletal muscle often used in treating spasticity

Connections: This review article discusses mechanisms leading to overproduction of uric acid in patients diagnosed with Lesch-Nyhan syndrome. This places importance on regulation of metabolic pathways, and illustrates how, a defective enzyme or lack of regulation can cause accumulation of an intermediate, in this case guanine and hypoxanthine, resulting in a diseased state. There was also a term mentioned in the article that we’ve discussed in class multiple times regarding regulation, and this is feedback inhibition. Feedback inhibition is the inhibition of an allosteric enzyme at the beginning of a metabolic sequence by the end product of the sequence. There are actually three feedback mechanisms involved in regulating the overall rate of de novo purine synthesis, one of which was briefly mentioned in this article. The reaction involving the conversion of PRPP to 5-Phosphoribosylamine by transfer of an amino group is inhibited by the end products of the pathway, IMP, AMP, and GMP. A second control mechanism is when excess GMP inhibits xanthylate synthesis from inosate. The third mechanism, that GTP is required to convert IMP to AMP and ATP is required to convert IMP to GMP considered to be a reciprocal substrate relationship. Feedback inhibition is used a tool for regulation in many pathways including glycolysis, gluconeogenesis, and the citric acid cycle. It was mentioned that the co-substrate referred to as PRPP plays a role in the purine salvage pathway. Throughout this entire course we’ve focused on properties of activated intermediates. This co-substrate, PRPP, is an activated intermediate because of the phosphate group and the presence of the phosphoanhydride bond, which can be cleaved to generate energy. Once an amino group donated by glutamine is attached to PRPP, 5-phosphoribosylamine is formed and the purine ring is built upon the structure of this sugar.

Article #3: Anaplerotic processes in human skeletal muscle during brief dynamic exercise

Main Focus: Although under normal conditions, anaplerotic reactions, which replenish tricarboxylic acid cycle intermediates, and cataplerotic reactions, which remove cycle intermediates, counteract each other mediating the constant concentration of tricarboxylic acid cycle intermediates (TCAIs), this does not seem to be the case during contraction of mammalian skeletal muscle. Under these circumstances the concentration of some TCAIs increase. The main focus of this article is to determine which mechanism plays the largest role and is most influential in the increase in TCAIs at the onset of exercise in human skeletal muscle. Possible mechanisms include the purine nucleotide cycle and reactions catalyzed by alanine aminotransferase, pyruvate carboxylase, glutamate dehydrogenase, malic enzyme, and phosphoenolpyruvate carboxykinase. The knee extensor exercise model was utilized in order to determine and compare concentrations of metabolites. The mechanism proposed to be responsible for the net increase in pool size of TCAIs during contraction was the purine nucleotide cycle which consists of three reactions. Throughout the cycle, GTP is consumed, aspartate is deaminated and NH3 along with fumarate are produced. When a competitive inhibitor of aspartate, hadacidin, was used to block the purine nucleotide cycle in the hindlimb muscle of a rat there was a 53% reduction in accumulation of malate and fumarate compared to control animals that weren’t treated with this inhibitor. Although this seems like strong evidence, there is controversy because of two reasons. There was no measurable change in aspartate concentrations during exercise which is required to reanimate IMP and produce fumarate, and there was only a small increase in NH3 formation. This indicates that the purine nucleotide cycle contributed only a minor amount to the increase in TCAI pool size. Instead, the alanine aminotransferase reaction may be the major anaplerotic reaction causing this increase in TCAI pool size in initial muscle contraction of humans.

New Terms: Tricarboxylic acid = organic acid containing three carboxyl groups Tricarboxylic acid cycle (TCA cycle) = cyclic system of enzymatic reactions for the oxidation of acetyl residues to carbon dioxide (also known as citric acid cycle or Krebs cycle) Carboxylation = introduction of a carboxyl group into a compound Decarboxylation = removal of carboxyl group from chemical compound, usually replacing it with hydrogen Cataplerotic reactions = reactions involved in disposal of tricarboxylic acid cycle (TCA cycle) (taken from Anaplerotic reactions = series of enzymatic reactions that replenish the pools of metabolic intermediates in the tricarboxylic acid cycle (TCA cycle)(taken from

Connections: In our study of the citric acid cycle we learned that the intermediates are drawn off to serve as biosynthetic precursors. For instance, ?-Ketoglutarate and oxaloacetate act as precursors of aspartate and glutamate, which are amino acids, and through these amino acids are used to build other amino acids and nucleotides. Oxaloacetate can be converted to glucose in gluconeogenesis and succinyl-CoA acts in synthesis of the porphyrin ring of heme groups. Citrate can also be siphoned off to synthesize fatty acids and sterols. When these intermediates are removed, they are replenished by anaplerotic reactions in order to keep the concentrations of the citric acid cycle intermediates constant. The anaplerotic reaction that is most essential to the proper functioning of the citric acid cycle is the carboxylation of pyruvate to form oxaloacetate catalyzed by pyruvate carboxylase, because the citric acid cycle requires oxaloacetate in order to function. The production of fumarate from aspartate in the purine nucleotide cycle also acts as an anaplerotic reaction to replenish an intermediate of the citric acid cycle.

MetaCyc Pathways:

Purine nucleotides de novo biosynthesis I

Purine nucleotides de novo biosynthesis II

de novo biosynthesis of pyrimidine ribonucleotides

Pyrimidine ribonucleotides interconversion

de novo biosynthesis of pyrimidine deoxyribonucleotides

Salvage pathways of purine and pyrimidine nucleotides

Salvage pathways of pyrimidine ribonucleotides

Salvage pathways of pyrimidine deoxyribonucleotides

Articles and Web Pages for Review and Inclusion


Peer-Reviewed Article #1:

'UPLC-ESI-TOFMS-Based Metabolomics and Gene Expression Dynamics Inspector Self-Organizing Metabolomic Maps as Tools for Understanding the Cellular Response to Ionizing Radiation

Anal. Chem., 2008, 80 (3), pp 665–674

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Enter your article summary here. Please note that the punctuation is critical at the start (and sometimes at the end) of each entry. It should be 300-500 words. What are the main points of the article? What questions were they trying to answer? Did they find a clear answer? If so, what was it? If not, what did they find or what ideas are in tension in their findings?

Relevance to a Traditional Metabolism Course

Enter a 100-150 word description of how the material in this article connects to a traditional metabolism course. Does the article relate to particular pathways (e.g., glycolysis, the citric acid cycle, steroid synthesis, etc.) or to regulatory mechanisms, energetics, location, integration of pathways? Does it talk about new analytical approaches or ideas? Does the article show connections to the human genome project (or other genome projects)?