The reactions of the phosphorylated pathway of L-serine biosynthesis: thermodynamic relationships in rabbit liver in vivo |
| |
| Authors: | K Lund D K Merrill R W Guynn |
| |
| Institution: | 1. Department of Psychiatry and Behavioral Sciences, University of Texas Medical School, P.O. Box 20708, Houston, Texas, U.S.A.;2. The University of Texas Health Science Center, Graduate School of Biomedical Sciences, Houston, Texas 77025 U.S.A.;3. Commissariat à l''Energie Atomique, Direction des Sciences du Vivant, institut de Recherches en Technologies et en Sciences pour le Vivant, Laboratoire de Physiologie Cellulaire et Végétale, F-38054 Grenoble, France;4. Université Grenoble Alpes, F-38054 Grenoble, France;5. Institut National de la Recherche Agronomique, USC1359, F-38054 Grenoble, France;6. INSERM, Laboratoire d''Etude de Dynamique des Protéomes, U880, F-38054 Grenoble, France;1. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA;2. Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA;3. Department of Cancer Biology, Department of Oncologic Pathology, and Blais Proteomics Center, Dana-Farber Cancer Institute, Boston, MA 02215, USA;4. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02215, USA;5. Department of Pathology, Brigham and Women’s Hospital, Boston, MA 02215, USA;6. Howard Hughes Medical Institute, Worcester, MA 01605, USA;1. Department of Surgery, Samuel Oschin Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA;2. Biostatistics and Bioinformatics Research Center, Samuel Oschin Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA;3. Department of BioMedical Sciences, Samuel Oschin Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA;4. Vancouver Prostate Centre, University of British Columbia, Vancouver, BC V6H 3Z6, Canada;5. Department of Pathology, Samuel Oschin Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA;6. Department of Medicine, Samuel Oschin Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA;7. Department of Surgery, University of Illinois College of Medicine at Urbana Champaign, Urbana, IL 61801, USA;8. College of Veterinary Medicine, Western University of Health Sciences, Pomona, CA 91766, USA;9. Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6, Canada;10. Department of Molecular and Cellular Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;11. Center for Molecular Medicine and Graduate Institute of Cancer Biology, China Medical University, Taichung 402, Taiwan;12. Department of Obstetrics and Gynecology, Samuel Oschin Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA;3. Biosciences Division, SRI International, Menlo Park, California 94025,;4. Department of Radiation Oncology, The James Comprehensive Cancer Center, Ohio State University, Columbus, Ohio 43210,;5. Department of Biology, Langara College, Vancouver, British Columbia V5W 2Z6, Canada,;6. Department of Pediatrics, UCLA School of Medicine, Los Angeles, California 90509,;12. SIDMAP, LLC, Los Angeles, California 90064 |
| |
| Abstract: | The thermodynamic relationships among the reactions of the phosphorylated pathway of L-serine biosynthesis have been determined in rabbit liver in vivo in different dietary states. The mass action ratios of the reactions involved were calculated from the concentrations of appropriate metabolites in freeze-clamped liver and compared with the equilibrium constants of the same reactions previously determined under physiological conditions. Toward this goal, a new, highly specific enzymatic assay for L-phosphoserine was developed to allow the accurate measurement of this intermediate in biological material. The level of L-phosphoserine, the immediate precursor of L-serine, varied significantly with diet, being 0.81, 0.38, and 0.21 mumol/g wet wt in the fed, and 24 h and 48 h fasted states, respectively. The tissue content of L-phosphoserine was also sensitive to anoxia, falling almost fivefold within 5 min after the liver was removed. Values of for the combined reactions of the first two steps of the pathway of L-serine biosynthesis D-3-phosphoglycerate dehydrogenase (EC 1.1.1.95) and L-phosphoserine aminotransferase (EC 2.6.1.52)] in livers from animals in different dietary states were calculated to be 1.2 X 10(-4) (fed), 1.4 X 10(-4) (24 h starved), and 0.70 X 10(-4) (48 h starved), all being very close to the value of the combined equilibrium constant of the same reactions (2.44 X 10(-4). Even when there were major changes in the individual components of, such as a fivefold drop in L-phosphoserine and a sevenfold fall in alpha-ketoglutarate following 5 min of anoxia, remained relatively unchanged (2.7 X 10(-4). Thus, it has been concluded that, in rabbit liver under most normal conditions, the combined reactions of D-3-phosphoglycerate dehydrogenase and L-phosphoserine aminotransferase remain very near equilibrium, and that almost all of the disequilibrium of the pathway, amounting to a delta G of -5.5 kcal/mol in the fed state, is at the last step, the L-phosphoserine phosphatase reaction (EC 3.1.3.3). |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
