Adenylosuccinate Explained

Adenylosuccinate, also known as succinyl-adenosine monophosphate (S-AMP), is an intermediate in the interconversion of purine nucleotides inosine monophosphate (IMP) and adenosine monophosphate (AMP). The enzyme adenylosuccinate synthase carries out the reaction of IMP to S-AMP in a 2 step mechanism,[1] requiring the input of energy from a phosphoanhydride bond from the hydrolysis of guanosine triphosphate (GTP)[2] first, followed by the addition of aspartate. This reaction needs Mg2+,[3] and is competitively inhibited by the subsequent product AMP in a negative feedback mechanism.[4] GTP, the product of another pathway from IMP, is used instead of adenosine triphosphate (ATP) as the phosphate source. The enzyme adenylosuccinate lyase carries out the reaction removing the carbon skeleton from S-AMP attached from aspartate, forming AMP and fumarate. The pathway from IMP to AMP is present across various prokaryotes and eukaryotes, and is linked to various diseases.[5] S-AMP has been observed to stimulate insulin production.[6]

See also

Notes and References

  1. Mehrotra . Sonali . Balaram . Hemalatha . 2007-11-06 . Kinetic characterization of adenylosuccinate synthetase from the thermophilic archaea Methanocaldococcus jannaschii . Biochemistry . 46 . 44 . 12821–12832 . 10.1021/bi701009y . 0006-2960 . 17929831.
  2. Figures 20.4 and 20.7 in Textbook of Biochemistry, with clinical correlations, Sixth Edition, Thomas M. Devlin, Ed., Wiley-Liss, Inc., New York, NY, 2006
  3. Iancu . Cristina V. . Borza . Tudor . Fromm . Herbert J. . Honzatko . Richard B. . 2002-10-25 . Feedback inhibition and product complexes of recombinant mouse muscle adenylosuccinate synthetase . The Journal of Biological Chemistry . 277 . 43 . 40536–40543 . 10.1074/jbc.M204952200 . free . 0021-9258 . 12186864.
  4. Book: Garrett . Reginald H. . Biochemistry . Grisham . Charles M. . 2017 . Cengage Learning . 978-1-305-57720-6 . 6th . Boston, MA . 927–940 . en.
  5. Marsac . Roxane . Pinson . Benoît . Saint-Marc . Christelle . Olmedo . María . Artal-Sanz . Marta . Daignan-Fornier . Bertrand . Gomes . José-Eduardo . 2019 . Purine Homeostasis Is Necessary for Developmental Timing, Germline Maintenance and Muscle Integrity in Caenorhabditis elegans . Genetics . 211 . 4 . 1297–1313 . 10.1534/genetics.118.301062 . 1943-2631 . 6456310 . 30700528.
  6. Gooding . Jessica R. . Jensen . Mette V. . Dai . Xiaoqing . Wenner . Brett R. . Lu . Danhong . Arumugam . Ramamani . Ferdaoussi . Mourad . MacDonald . Patrick E. . Newgard . Christopher B. . 2015-10-06 . Adenylosuccinate Is an Insulin Secretagogue Derived from Glucose-Induced Purine Metabolism . Cell Reports . 13 . 1 . 157–167 . 10.1016/j.celrep.2015.08.072 . 2211-1247 . 4598307 . 26411681.

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