3 Adenylate kinaseRule: the balance of ATP, ADP, and AMP in a cell is controlled by adenylate kinase. Reactions that elevate ADP elevate AMP, a major allosteric regulator.EquationK =[ATP][AMP][ADP]22ADPATP+AMPBiological Reality100ATP102ADPAMPRule:A small change in ATP will have a strongly magnifying effect on ADP or AMP concentrations in the cell
4 ATP ATP Examples in Working Muscle ADP K = [ATP][AMP] [ADP]2 ADP 100 0.1 mM1 mM0.02 mMIf ATP concentration drops by 10%, adenylate kinase will readjust the levels of ADP and AMP to compensate100%-10%>400%ATPADPAMP0.2 mM0.9 mM~0.1 mM
6 Fructose-2,6-Bisphosphate A Major Allosteric RegulatorSynthesized by Phosphofructokinase-2Destroyed by Fructose-2,6-BisphosphatasePowerful Activator of GlycolysisPowerful Inhibitor of GluconeogenesisNot an Intermediate in any Pathway
7 O O O3POCH2 OH Fructose-6-P Fructose-1,6BP PO3= CH2OH 6 2 OH CH2OH -D-Fructose-2,6BP1
9 Fructose-2,6-bisPO4 (F2,6BP) the most important allosteric effector thatregulates glycolysis-gluconeogenesisActivates PFK-1 Inhibits F1,6-bisPtaseF2,6BP level controlled by rates of synthesis and degradationF6PF2,6BPPFK-2Both in Same ProteinFBPtase-2F6PF2,6BP(-)Citrate(-)F6P(+)AMP(+)Glycerol-3-PO4PFK-2FBP-2(+)F6PGlycolysisGluconeogenesis
10 Hormonal Control of F2,6BP See P. 458Hormonal Control of F2,6BPGlucagonEpinephrineLivercAPKcAMPPFK2 (a)PFK2 (b)FBPase2 (b)FBPase2 (a)ATPADPPcAPKKinasePhosphataseInhibits glycolysisStimulatesgluconeogenesiscAMPIN LIVER: cAMP activates the phosphatase that destroys F2,6BPand inhibits the kinase that makes F2,6BP. The combined effect isto stimulate gluconeogenesis in liver.
11 FUTILE CYCLING F6P PO4 H20 ATP ADP F1,6BP At steady-state, net reaction is:ATP + H2OADP + PO4TAKE HOME: To prevent futile cycling, rates ofsynthesis and degradation in an ATP-dependent stepmust not be the same.
12 INSULIN VS GLUCAGON See Page 686 in Textbook Insulin: Stimulates Glycolysis, Glycogen SynthesisInsulin is designed to remove blood glucose andallow cells to metabolized the glucose or make glycogenInsulin inhibits gluconeogenesisGlucagon: Promotes Gluconeogenesis, Glycogen BreakdownGlucagon is designed to raise blood glucose andassist liver in controlling blood glucose levelsElevates cAMP in liver and stimulates proteinphosphorylationTargets: PEPCKGlycogen SynthaseFBPtase-2PKGlycogen Phosphorylase
13 Amino Sugars Synthesized from D-fructose Amine group donated by glutamineAcetylatedFound in GAGS, proteoglycans and glycoproteinsExamples are N-acetylglucosamine, N-acetylgalactosamine, N-acetylneuraminic acid (Sialic acid)
15 3-Stages of Glycoprotein Synthesis Assembly of oligosaccharidechains on DolicholAssembly of polypeptidechain with Asn-X-Ser/Thron ribosomesFinal tailoring ofoligosaccharidechains in GolgiFinished product for secretionor intracellular targeting
16 Energy in Glucose (Aerobic) Glucose F1,6BP: ATPF1,6BP 2 Pyr: ATP2 NADH ATPMitochondria2Pyr 2Acetyl-CoA: 2NADH = 6 ATP2Acetyl-CoA 4CO ATP38 ATPC6H12O O2 6CO H2O Go’= -2,850 kJ/molConserved = 38 ATP x 30.5 kJ/ATP = 1,159 kJEfficiency = 40.7%
17 Energy in Succinate Succinate Fumarate: 1 FADH2 = 2 ATP Fumarate Malate: 0Malate OAA: 1 NADH = 3 ATPOAA 4CO2: 2 cycles = 24 ATPTotal = 29 ATP