Chapter 15 (abbreviated): Principles of Metabolic Regulation

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Chapter 15 (abbreviated) Principles of Metabolic
Regulation

• CHEM 7784
• Biochemistry
• Professor Bensley

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CHAPTER 15 (Abbreviated) Principles of Metabolic
Regulation
Todays Objectives (To learn and understand the)

• Principles of regulation in biological systems
• Glycolysis vs. gluconeogenesis which one is
  turned on and which one is turned off?

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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
In this chapter, we learned that

• 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