The Nobel Prize in Physiology or Medicine 1953 "for his discovery of the citric acid cycle” 1937 "for his discovery of co-enzyme A and its importance for intermediary metabolism" Sir Hans Adolf Krebs Fritz Albert Lipmann Sheffield University United Kingdom Harvard Medical School Boston, MA, USA At the University of Freiburg (1932), Krebs discovered (with the German biochemist Kurt Henseleit) a series of chemical reactions (now known as the urea cycle) by which ammonia is converted to urea in mammalian tissue; GLICOLISI citoplasma CH3-CO~CoA (acetil ~ COA) mitocondrio Ciclo di Krebs o Ciclo degli acidi tricarbiossilici o Ciclo del citrato Via metabolica finale comune - glucosio - acidi grassi - amminoacidi ANAEROBIOSI GLUCOSIO 2 LATTATO 2 ATP AEROBIOSI GLUCOSIO 2 PIRUVATO 2 NADH 2 ATP 5 ATP 2 NADH 5 ATP 2 ACETIL-CoA 3 NADH + H+ 2 x 1 FADH2 1 GTP 7,5 ATP 2 x 1,5 ATP 1 ATP 10 ATP 20 ATP TOT 32 ATP CO2 BIOSINTESI GLUCOSIO piruvato principale via di entrata aspartato -BIOSINTESI LIPIDI -acidi grassi - colesterolo BIOSINTESI UREA fenilalanina tirosina BIOSINTESI E CATABOLISMO AMMINOACIDI metab. extra epatico corpi chetonici BIOSINTESI EME - porfirina Val Ile Met glutammato Ac grassi a catena dispari Controllo: rapporto mitocondriale NAD+/NADH e stato energetico della cellula 3 deidrogenasi inibite da alti livelli NADH e bassi livelli di NAD+ acetil-CoA isocitrato (deidrogenasi) ossalacetato Inibita NADH Attivata ADP Inibita NADH -chetoglutarato (deidrogenasi) malato (deidrogenasi) Inibita NADH Inibita succinil-CoA succinil-CoA