Allosterically activated by fructose16bisphosphate increase flow through glycolysis Allosterically inhibited by signs of abundant energy supply all tissues ATP acetylCoA and longchain fatty acids ID: 908719
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Slide1
Regulation of Pyruvate Kinase
Allosterically activated by fructose-1,6-bisphosphateincrease flow through glycolysisAllosterically inhibited by signs of abundant energy supply (all tissues)ATP acetyl-CoA and long-chain fatty acidsalanine (enough amino acids)Inactivated by phosphorylation in response to signs of glucose depletion (glucagon) (liver only)Glucose from liver is exported to the brain and other vital organs.
Slide2Regulation of Pyruvate Kinase
Slide3Two Alternative Fates for Pyruvate
Pyruvate can be a source of new glucose.store energy as glycogengenerate NADPH via pentose phosphate pathwayPyruvate can be a source of acetyl-CoA.store energy as body fatmake ATP via citric acid cycleAcetyl-CoA stimulates glucose synthesis via gluconeogenesis by activating pyruvate carboxylase.
Slide4Two Alternative Fates for Pyruvate
Slide5The Amount of Many Metabolic Enzymes Is Controlled by Transcription
TABLE 15-5Some of the Many Genes Regulated by Insulin
Change in gene expression
Role in glucose metabolism
Increased expression
Hexokinase
II
Hexokinase
IV
Phosphofructokinase-1 (PFK-1)
PFK-2/FBPase-2
Pyruvate kinase
Essential for
glycolysis
, which consumes glucose for energy
Glucose 6-phosphate dehydrogenase
6-Phosphogluconate dehydrogenase
Malic
enzyme
Produce NADPH, which is essential for conversion of glucose to lipids
ATP-citrate
lyase
Pyruvate dehydrogenase
Produce acetyl-CoA, which is essential for conversion of glucose to lipids
Acetyl-CoA
carboxylase
Fatty acid synthase complex
Stearoyl
-CoA dehydrogenase
Acyl
-CoA–glycerol
transferases
Essential for conversion of glucose to lipids
Decreased expression
PEP
carboxykinase
Glucose 6-phosphatase (catalytic subunit)
Essential for glucose production by
gluconeogenesis
Slide6ChREBP Activates Transcription in Response to Glucose
Slide7FOXO1 Activates Transcription in Response to Insulin (High Blood Glucose)
Slide8The Transcription of Many Genes Is Controlled by Many Different Factors
Slide9Glucose Can Be Stored for Later Use as Glycogen
Glycogen is a branched polymer of
α
(1
4)-linked glucose with
α
(16) linkages every 12 to 14 glucose units.
Glycogen storage occurs mainly in the liver and muscle.
Glycogen is degraded to glucose units for use in energy production.
Glycogen can be made from excess blood glucose or recycling of glucogenic metabolites like lactate or certain amino acids.
Slide10Glucose Residues Are Removed from Glycogen by Glycogen Phosphorylase
Slide11Dealing with Branch Points in Glycogen
Glycogen phosphorylase
works on nonreducing ends until it reaches four residues from an (
1 6
) branch point.
Debranching enzyme
transfers a block of three residues to the nonreducing end of the chain.
Debranching enzyme
cleaves the single remaining (
16
)-linked glucose, which becomes a free glucose unit (i.e., NOT glucose-1-phosphate).
Slide12Glucose-1-Phosphate Must Be Isomerized to Glucose-6-Phosphate for Metabolism
Phosphoglucomutase performs this reaction via a mechanism similar to phosphoglycerate mutase.
Slide13Glucose-6-Phosphate Is Dephosphorylated in the Liver for Transport Out of the Liver
Glucose-6-phosphatase is sequestered in the ER lumen, which allows use of concentration gradients for glucose and glucose-6-phosphate) to control flux out of the liver.
Slide14Glycogen Synthesis from Glucose Occurs in Multiple Steps
Synthesis of glycogen requires more enzymes and metabolic intermediates than glycogen degradation.
Blood glucose must be:
phosphorylated
labeled with UDP
added to glycogen
Multiple steps allow for multiple points in regulation.
Slide15Glycogen Is Synthesized by
Glycogen Synthase
Slide16UDP-Glucose Is the Substrate
for Glycogen Synthase
Slide17Glucose-1-Phosphate Is the Substrate
for NDP-Sugar Pyrophosphorylase
Phosphoglucomutase
is reversible.
In glycogen degradation, glucose-1-phosphate is converted to glucose-6-phosphate.
In glycogen synthesis, glucose-6-phosphate is converted to glucose-1-phosphate.
Slide18Synthesis of Branches in Glycogen
Slide19Glycogenin Starts a New Glycogen Chain
Slide20General Structure of a Glycogen Particle
Slide21Integration of Glycogen Synthesis and Degradation
Glucose
Glucose-6-phosphate
Glucose-1-phosphate
Glycogen
UDP-glucose
Glucose-6-phosphatase
Hexokinase
Phosphoglucomutase
Glycogen phosphorylase
UDP-glucose pyrophosphorylase
Glycogen synthase
Like Glycolysis and Gluconeogenesis, regulation occurs at irreversible points in the pathway
Slide22Control of Glycogen Breakdown
Glucogon/epinephrine signaling pathwaystarts phosphorylation cascade vis cAMPactivates glycogen phosphorylaseGlycogen phosphorylase cleaves glucose residues off glycogen, generating glucose-1-phosphate.
Slide23Epinephrine and Glucagon Stimulate Breakdown of Glycogen
Slide24Control of Glycogen Synthesis
Insulin-signaling pathwayincreases glucose import into musclestimulates the activity of muscle hexokinase activates glycogen synthaseIncreased hexokinase activity enables activation of glucose.Glycogen synthase makes glycogen for energy storage.
Slide25Flow to Glycogen Synthase Is Controlled by Glucose Uptake and Phosphorylation
Slide26Glycogen Synthase Is Controlled
by Phosphorylation
Slide27Control of Carbohydrate Metabolism in the Liver
Slide28Control of Carbohydrate Metabolism
in the Liver versus the Muscle
Slide29TABLE 1
Glycogen Storage Diseases of Humans
Type (name)
Enzyme affected
Primary organ/cells affected
Symptoms
Type 0
Glycogen synthase
Liver
Low blood glucose, high
ketone
bodies, early death
Type
Ia
(von
Gierke
)
Glucose 6-phosphatase
Liver
Enlarged liver, kidney failure
Type
Ib
Microsomal
glucose 6-phosphate
translocase
Liver
As in type
Ia
; also high susceptibility to bacterial infections
Type
Ic
Microsomal
P
i
transporter
Liver
As in type
Ia
Type II (
Pompe
)
Lysosomal
glucosidase
Skeletal and cardiac muscle
Infantile form: death by age 2; juvenile form: muscle defects (
myopathy
); adult form: as in muscular dystrophy
Type
IIIa
(Cori or Forbes)
Debranching
enzyme
Liver, skeletal and cardiac muscle
Enlarged liver in infants;
myopathy
Type
IIIb
Liver
debranching
enzyme (muscle enzyme normal)
Liver
Enlarged liver in infants
Type IV (Andersen)
Branching enzyme
Liver, skeletal muscle
Enlarged liver and spleen,
myoglobin
in urine
Type V (
McArdle
)
Muscle
phosphorylase
Skeletal muscle
Exercise-induced cramps and pain;
myoglobin
in urine
Type VI (Hers)
Liver
phosphorylase
Liver
Enlarged liver
Type VII (
Tarui
)
Muscle PFK-1
Muscle, erythrocytes
As in type V; also hemolytic anemia
Type
VIb
, VIII, or IX
Phosphorylase
kinase
Liver, leukocytes, muscle
Enlarged liver
Type XI (
Fanconi
-Bickel)
Glucose transporter (GLUT2)
Liver
Failure to thrive, enlarged liver, rickets, kidney dysfunction
Slide30Chapter 15: Summary
living organisms regulate the flux of metabolites through metabolic pathways byincreasing or decreasing enzyme concentrationsactivating or inactivating key enzymes in the pathwaythe activity of key enzymes in glycolysis and gluconeogenesis is tightly and coordinately regulated via various activating and inhibiting metabolitesglycogen synthesis and degradation is regulated by hormones insulin, epinephrine, and glucagon that report on the levels of glucose in the body
In this chapter, we learned that: