Chapter 15 (abbreviated):
Principles of Metabolic
Regulation
CHEM 7784
Biochemistry
Professor Bensley
CHAPTER 15 (Abbreviated)
Principles of Metabolic Regulation
Today’s 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”?
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
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
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
Factors that Affect the Activity of
Enzymes
Some Enzymes in the Pathway
Limit the Flux of Metabolites
More than Others
• Hexokinase and
phosphofructokinase
are appropriate
targets for regulation
of glycolytic flux
Elasticity Coefficient Measures
the Responsiveness to Substrate
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
UDP-Glucose
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
Glycolysis
vs.
Gluconeogenesis
Regulation of
Phosphofructokinase-1
• The conversion of
fructose-6-phosphate to
fructose 1,6bisphosphate is the
commitment step in
glycolysis
• ATP is a negative
effector
– Do not spend glucose in
glycolysis if there is
plenty of ATP
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
Regulation by Fructose 2,6Bisphosphate
• F26BP activates
phosphofructokinase
(glycolytic enzyme)
• F26BP inhibits fructose
1,6-bisphosphatase
(gluconeogenetic
enzyme)
Regulation by Fructose 2,6Bisphosphate
• Go glycolysis if F26BP is high
• Go gluconeogenesis if F26BP is low
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