chapter 15 (abbreviated): principles of metabolic regulation chem 7784 biochemistry professor...
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Chapter 15 (abbreviated): Principles of Metabolic
RegulationCHEM 7784
Biochemistry
Professor Bensley
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CHAPTER 15 (Abbreviated) Principles of Metabolic Regulation
– Principles of regulation in biological systems – Glycolysis vs. gluconeogenesis – which one is
turned “on” and which one is turned “off”?
Today’s Objectives: (To learn and understand the)
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Homeostasis
• Organisms maintain homeostasis by keeping the concentrations of most metabolites at steady state
• In steady state, the rate of synthesis of a metabolite equals the rate of breakdown of this metabolite
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Principles of Regulation
• The flow of metabolites through the pathways is regulated to maintain homeostasis
• Sometimes, the levels of required metabolites must be altered very rapidly– Need to increase the capacity of glycolysis during the
action
– Need to reduce the capacity of glycolysis after the action
– Need to increase the capacity of gluconeogenesis after successful action
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Feedback Inhibition
• In many cases, ultimate products of metabolic pathways directly or indirectly inhibit their own biosynthetic pathways– ATP inhibits the commitment step of
glycolysis
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Factors that Affect the Activity of Enzymes
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Some Enzymes in the Pathway Limit the Flux of Metabolites
More than Others
• Hexokinase and
phosphofructokinase
are appropriate
targets for regulation
of glycolytic flux
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Elasticity Coefficient Measures the Responsiveness to Substrate
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Control of Glycogen Synthesis
• Insulin signaling pathway– increases glucose import into muscle
– stimulates the activity of muscle hexokinase
– activates glycogen synthase
• Increased hexokinase activity enables activation of glucose
• Glycogen synthase makes glycogen for energy storage
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UDP-Glucose
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Isozymes may Show Different Kinetic Properties
• Isozymes are different enzymes that catalyze the same reaction
• They typically share similar sequences
• Their regulation is often different
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Glycolysis vs.
Gluconeo-genesis
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Regulation of Phosphofructokinase-1
• The conversion of fructose-6-phosphate to fructose 1,6-bisphosphate is the commitment step in glycolysis
• ATP is a negative effector– Do not spend glucose in
glycolysis if there is plenty of ATP
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Regulation of Phosphofructokinase 1 and
Fructose 1,6-Bisphosphatase• Go glycolysis if AMP is high and ATP is low• Go gluconeogenesis if AMP is low
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Regulation by Fructose 2,6-Bisphosphate
• F26BP activates phosphofructokinase (glycolytic enzyme)
• F26BP inhibits fructose 1,6-bisphosphatase (gluconeogenetic enzyme)
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Regulation by Fructose 2,6-Bisphosphate
• Go glycolysis if F26BP is high• Go gluconeogenesis if F26BP is low
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Chapter 15: Summary
• living organisms regulate the flux of metabolites via metabolic pathways by– increasing or decreasing enzyme concentrations
– activating or inactivating key enzymes in the pathway
• the activity of key enzymes in glycolysis and gluconeogenesis is tightly regulated via various activating and inhibiting metabolites
In this chapter, we learned that: