title: Arteriovenous Blood Metabolomics: A Readout of Intra-Tissue Metabostasis.
abstract: The human circulatory system consists of arterial blood that delivers nutrients to tissues, and venous blood that removes the metabolic by-products. Although it is well established that arterial blood generally has higher concentrations of glucose and oxygen relative to venous blood, a comprehensive biochemical characterization of arteriovenous differences has not yet been reported. Here we apply cutting-edge, mass spectrometry-based metabolomic technologies to provide a global characterization of metabolites that vary in concentration between the arterial and venous blood of human patients. Global profiling of paired arterial and venous plasma from 20 healthy individuals, followed up by targeted analysis made it possible to measure subtle (<2 fold), yet highly statistically significant and physiologically important differences in water soluble human plasma metabolome. While we detected changes in lactic acid, alanine, glutamine, and glutamate as expected from skeletal muscle activity, a number of unanticipated metabolites were also determined to be significantly altered including Krebs cycle intermediates, amino acids that have not been previously implicated in transport, and a few oxidized fatty acids. This study provides the most comprehensive assessment of metabolic changes in the blood during circulation to date and suggests that such profiling approach may offer new insights into organ homeostasis and organ specific pathology.
authors.affiliation: Center for Metabolomics and Mass Spectrometry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Julijana
authors.initials: J
authors.lastname: Ivanisevic
authors.affiliation: 1] Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, MEM-180, La Jolla, California 92037, United States [2] Anticoagulation Services, Scripps Clinic and Scripps Green Hospital, 10666 North Torrey Pines Road, W207, La Jolla, California 92037, United States.
authors.forename: Darlene
authors.initials: D
authors.lastname: Elias
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, MEM-180, La Jolla, California 92037, United States.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Deguchi
authors.affiliation: Anticoagulation Services, Scripps Clinic and Scripps Green Hospital, 10666 North Torrey Pines Road, W207, La Jolla, California 92037, United States.
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Averell
authors.affiliation: Center for Metabolomics and Mass Spectrometry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Kurczy
authors.affiliation: Center for Metabolomics and Mass Spectrometry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Caroline H
authors.initials: CH
authors.lastname: Johnson
authors.affiliation: Center for Metabolomics and Mass Spectrometry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Ralf
authors.initials: R
authors.lastname: Tautenhahn
authors.affiliation: Center for Metabolomics and Mass Spectrometry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Zhengjiang
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Departments of Medicine and Pharmacology, University of California, 9500 Gilman Drive, MC 0613, La Jolla, California 92037, United States.
authors.forename: Jeramie
authors.initials: J
authors.lastname: Watrous
authors.affiliation: Departments of Medicine and Pharmacology, University of California, 9500 Gilman Drive, MC 0613, La Jolla, California 92037, United States.
authors.forename: Mohit
authors.initials: M
authors.lastname: Jain
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, MEM-180, La Jolla, California 92037, United States.
authors.forename: John
authors.initials: J
authors.lastname: Griffin
authors.affiliation: Departments of Chemistry, Genetics, and Medicine, Washington University, One Brookings Drive, St. Louis, Missouri 63130, United States.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Patti
authors.affiliation: 1] Center for Metabolomics and Mass Spectrometry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States [2] Departments of Chemistry, Molecular and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Gary
authors.initials: G
authors.lastname: Siuzdak
mesh_terms: D000328:Adult; D000596:Amino Acids / Q000097:blood*; D001786:Blood Glucose / Q000378:metabolism*; D005260:Female; D006801:Humans; D019344:Lactic Acid / Q000097:blood*; D008297:Male; D055432:Metabolomics; D010100:Oxygen / Q000097:blood*
chemical_list: D000596:Amino Acids; D001786:Blood Glucose; D019344:Lactic Acid; D010100:Oxygen