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Metabolic Pathways
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1.Sequential biochemical reactions during synthesis or degradation of metabolite in living cells
2. dedicated functions
3.represented as a map
4.interconnected
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General Features of Metabolic Pathways
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Metabolites flow through various steps of a pathway at the same rate
rate of formation= rate of degradation
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What is a "steady state"
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Body trys to maintain a balance or "normal" range
steady state concentrations are physiologically relevant
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Homeostasis
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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
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All metabolic reactions ______ equilibrium
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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
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Common Pathways of Regulating Enzymes
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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
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Why regulate glucose levels?
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Hyperglycemia: water loss from tissue,dehydration, hyperosmolar coma
Hypoglycemia: dizziness,coma, death
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Adenine nucleotides in metabolic regulation
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Relatively small change in concentration of ATP may cause ver large change in AMP concentration, affecting many reactions
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Pathways for AMPK
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Sensitve to levels of AMP in the cell
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Regulation of Phosphofructokinase-1(PFK1)
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Commitment step in glycolysis
PFK1 sensitive to ATP
LOW ATP activateds PFK1; glycolysis go
High ATP slows down PFK; glycolysis slows down(phos inhibited)
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Regulation of phosphofructokinase 1 & Fructose 1,6-Biphosphate(Draw)
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Glycolysis good when AMP is high and ATP is low
gluconeogensis is stimulated if AMP is low
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Regulation of glucose metabolism-Liver*
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Hexokinase IV
km for glucose> 15mM
no effect of G-6-P
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Regulation of glucose metabolism- Heart
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Hexokinase I
km for glucose< 1mM
inhibtied by G-6-P
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Reciprocal activation of Hexokinase IV
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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
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Regluation of glycolyssi by pyruvate kinase(DRAW)
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Pyruvated kinase:L and M isozymes
Isozymes respond differently to regulation by glucagon
only liver isozyme subject of phosphorylation and dephosphorylation
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