Principles of Metabolic Regulation

Chapter 15

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Cards In This Set

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Metabolic Pathways
1.Sequential biochemical reactions during synthesis or degradation of metabolite in living cells 2. dedicated functions 3.represented as a map 4.interconnected
General Features of Metabolic Pathways
Metabolites flow through various steps of a pathway at the same rate rate of formation= rate of degradation
What is a "steady state"
Body trys to maintain a balance or "normal" range steady state concentrations are physiologically relevant
Homeostasis
Maintenance of a dynamic steady state by regulatory mechaism that compensate for changes in external circumstances regulated coordinately lack or loss of regulation can be hazardous
All metabolic reactions ______ equilibrium
Metabolic reactions are not at equilibrium reaction in which forward & reverse rates differ only slightly, are near-equilibrium reaction in which forward and reverse rates differ substantially, non-equilibrium reactions far from equilibrium are common points of regulation
Common Pathways of Regulating Enzymes
1. EC signal 2.transcription of genes 3. mRNA degradation 4.mRNA translation on ribosome 5. protein degration 6.enzyme sequestered in subcellular organelle 7.enzyme binds to substrate 8. enzymes binds to ligand causes allosteric effect 9. enzymes phosphorylates 10. enzymes combing with regulatory protein
Why regulate glucose levels?
Hyperglycemia: water loss from tissue,dehydration, hyperosmolar coma Hypoglycemia: dizziness,coma, death
Adenine nucleotides in metabolic regulation
Relatively small change in concentration of ATP may cause ver large change in AMP concentration, affecting many reactions
Pathways for AMPK
Sensitve to levels of AMP in the cell
Regulation of Phosphofructokinase-1(PFK1)
Commitment step in glycolysis PFK1 sensitive to ATP LOW ATP activateds PFK1; glycolysis go High ATP slows down PFK; glycolysis slows down(phos inhibited)
Regulation of phosphofructokinase 1 & Fructose 1,6-Biphosphate(Draw)
Glycolysis good when AMP is high and ATP is low gluconeogensis is stimulated if AMP is low
Regulation of glucose metabolism-Liver*
Hexokinase IV km for glucose> 15mM no effect of G-6-P
Regulation of glucose metabolism- Heart
Hexokinase I km for glucose< 1mM inhibtied by G-6-P
Reciprocal activation of Hexokinase IV
1.glucose and fructose-6-P induce translocation of hexokinase IV to cytoplasm or nucelus 2. translocation ismediated by interaction of hexokinase IV with a regulatory nucelar protein
Regluation of glycolyssi by pyruvate kinase(DRAW)
Pyruvated kinase:L and M isozymes Isozymes respond differently to regulation by glucagon only liver isozyme subject of phosphorylation and dephosphorylation