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Authors: Pallavi Subhraveti Ron Caspi Peter Midford Peter D Karp An online version of this diagram is available at BioCyc.org. Biosynthetic pathways are positioned in the left of the cytoplasm, degradative pathways on the right, and reactions not assigned to any pathway are in the far right of the cytoplasm. Transporters and membrane proteins are shown on the membrane. Ingrid Keseler Periplasmic (where appropriate) and extracellular reactions and proteins may also be shown. Pathways are colored according to their cellular function. Gcf_009720545Cyc: Gimesia maris DSM 8797 Cellular Overview Connections between pathways are omitted for legibility.

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Annotation-1 Annotation-1
Annotation-1 Baseline Resuscitation Normal Saline Resuscitation PFP Shock Annotation-1 Aminoacids Arginine and proline metabolism Carnitine and fatty acid metabolsim Glutamate metabolism Glycerophospholipid biosynthesis Glycolysis and sugars GSH homeostasis GSH homeostasis/Glyoxlate Hexosamine Indole and Tryptophan Nucleotides Other Panthothenate metabolism Pentose Phosphate Pathway Serine biosynthesis and one-carbon metabolism Signaling Sulfur metabolism TCA cycle urea cycle relative row min row max Baseline_14 Baseline_16 Baseline_13 Baseline_15 Baseline_22 Baseline_2 Baseline_12 Baseline_3 Baseline_4 Baseline_9 Baseline_7 Baseline_8 Shock_13 Shock_12 Shock_15 Shock_22 Shock_14 Shock_16 Shock_2 Shock_3 Shock_7 Shock_4 Shock_8 Shock_9 Res_NS_14 Res_NS_13 Res_NS_16 Res_NS_12 Res_NS_22 Res_NS_15 Res_PFP_2 Res_PFP_3 Res_PFP_7 Res_PFP_4 Res_PFP_8 Res_PFP_9 Annotation-1 Annotation-1 Annotation Annotation-1 L-Arginine Aminoacids L-Isoleucine Aminoacids Leucine Aminoacids L-Cysteine Aminoacids L-Alanine Aminoacids L-Aspartate Aminoacids L-Glutamate Aminoacids L-Glutamine Aminoacids L-Histidine Aminoacids L-Lysine Aminoacids L-Methionine Aminoacids L-Tyrosine Aminoacids L-Asparagine Aminoacids L-Threonine Aminoacids L-Cystine Aminoacids L-Serine Aminoacids L-Proline Aminoacids L-Valine Aminoacids L-Tryptophan Aminoacids Glycine Aminoacids L-Kynurenine Aminoacids L-Phenylalanine Aminoacids CMP Nucleotides 6-Hydroxynicotinate Nucleotides 5-6-Dihydrouracil Nucleotides AMP Nucleotides dAMP Nucleotides GMP Nucleotides Guanine Nucleotides 2-5-Dihydroxypyridine
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35 Disorders of Purine and Pyrimidine Metabolism
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Clinical Symptoms of Defects in Pyrimidine Metabolism
ClinicalClinical symptomssymptoms ofof DefectsDefects inin pyrimidinepyrimidine metabolismmetabolism Birgit Assmann Department of General Pediatrics Universtiy Children‘s Hospital Düsseldorf, Germany Overview • Biosynthesis: UMP Synthase • Degradation: –– PyrimidinePyrimidine 55‘‘--Nucleotidase(UMPNucleotidase(UMP--Hydrolase)Hydrolase) – [Thymidine-Phosphorylase, mitochondrial] –– DihydropyrimidineDihydropyrimidine DehydrogenaseDehydrogenase –– DihydropyrimidinaseDihydropyrimidinase –– UreidopropionaseUreidopropionase HCO3+gluNH2 carbamoyl-P orotic acid OMP OPRT UMP OD UMPS UMPSUMPS == uridinemonophosphateuridinemonophosphate synthasesynthase Bifunctional enzyme (one gene): a) Orotate phosphoribosyl transferase (OPRT) b) Orotidine decarboxylase (OD) UMPS deficiency • = Hereditary orotic aciduria Hallmarks:Hallmarks: - MegaloblasticMegaloblastic anemiaanemia inin infantsinfants >> IfIf untreateduntreated:: FailureFailure toto thrivethrive PsychomotorPsychomotor retardationretardation • Therapy: uridine (≥100-150 mg/kg/d) Defects of pyrimidine degradation • Pyrimidine 5‘-Nucleotidase deficiency - chronic hemolytic anemia + basophilic stippling of erythrocytes • Thymidine phosphorylase deficiency = MNGIE=Mitoch. NeuroGastroIntestinal Encephalomyopathy Mitochondrial disorder with elevatedelevated urinaryurinary thymidinethymidine excretionexcretion HCO3+gluNH2 carbamoyl-P orotic acid OMP TMP UMP UMPS thymidine cytosolic 5‘- uridine Thym. Nucleotidase phosphor ylase thymine uracil Pyrimidine 5‘-Nucleotidase- SuperactivitySuperactivity • Existence
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Lc and Lc-Free Mass Spectrometry Applications in Non-Targeted Metabolomics for Disease Detection and Early Prediction
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Behavior of Activities of Thymidine Metabolizing Enzymes in Human Leukemia-Lymphoma Cells1
[CANCER RESEARCH 49. 1090-1094. March I, 1989] Behavior of Activities of Thymidine Metabolizing Enzymes in Human Leukemia-Lymphoma Cells1 Taiichi Shiotani, Yasuko Hashimoto, Terukazu Tanaka, and Shozo Irino First Department of Internal Medicine, Kagawa Medical School, Ikenobe, Miki, Kagawa, 761-07, Japan ABSTRACT 7). These observations indicate the importance of this catabolic enzyme for dThd utilization. Thymidylate, an important pre The behavior of the activities of thymidine metabolizing enzymes, cursor of DNA synthesis, also may be produced by the de novo dihydrothymine dehydrogenase (EC 1.3.1.2) and thymidine phosphoryl- pathway through dTMP synthase. The correlation between cell ase (EC 2.4.2.4) for thymidine degradation, thymidine kinase (EC proliferation and dThd kinase (3, 4, 6, 8, 9) or dTMP synthase 2.7.1.75) and thymidylate synthase (EC 2.1.1.45) for DNA synthesis, was elucidated in cytosolic extracts from normal human lymphocytes and (8, 10, 11) has been demonstrated. The enhanced capacity for 13 human leukemia-lymphoma cell lines. In the normal human lympho the salvage pathway in leukemia (12, 13) appears to limit the cytes, the activities of dihydrothymine dehydrogenase, thymidine phos- antitumor effectiveness of antimetabolites of de novo pyrimidine phorylase, thymidine kinase, and thymidylate synthase were 6.88, 796, biosynthesis. The enzymic capacities of the de novo and salvage 0.30, and 0.29 nmol/h/mg protein, respectively. In leukemia-lymphoma pathways and dThd catabolism have not been determined si cell lines, the activities of synthetic enzymes, thymidine kinase, and multaneously in human leukemia-lymphoma cells. Therefore, thymidylate synthase, increased two- to 79-fold and 22- to 407-fold of the elucidation of the behavior of the enzymic capacities in the the normal lymphocyte values.
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British Journal of Nutrition (2015), 113, 560–573 Doi:10.1017/S0007114514004000 Q the Authors 2015
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1 Synthesis of C-2 and C-6 Functionalized
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Role of Glutathione Metabolism in Host Defense Against Borrelia
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