Summary of Metabolic Pathways

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Summary of Metabolic Pathways
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Metabolic Profile Brain
Fuel(s) - glucose is prime fuel uses
120g/day Fuel use(s) - active transport (Na,
K ), biosynthesis Glucose uptake - transporter
half-saturated at 1.6 mM normal blood glucose
level 5 mM (90mg) hexokinase saturated at
0.5 mM hypoglycemic danger level 2.2 mM
(40mg) Main metabolic pathways - totally aerobic
metabolism glycolysis, citric acid cycle, ETS
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Metabolic Profile Skeletal Muscle
Fuel(s) - Resting muscle - fatty
acids Highly-active muscle - glucose from
glycogen produces lactate Fuel use(s) -
contraction, active transport (Ca2) Main
metabolic pathways - Resting muscle
(aerobic) fatty acid oxidation, citric
acid cycle, ETS Highly-active muscle (anaerobic)
glycogenolysis, glycolysis
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Metabolic Profile Heart Muscle
Fuel(s) - main fuel fatty acids Fuel use(s) -
contraction, active transport (Ca2) Main
metabolic pathways - totally aerobic
metabolism fatty acid oxidation, citric acid
cycle, ETS
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Metabolic Profile Adipose Tissue
Fuel(s) - major fuels glucose, fatty acids
Fuel use(s) - biosynthesis of triacylglycerols,
fatty acid synthesis (high blood glucose)
Main metabolic pathways - glycolysis, fatty acid
oxidation, citric acid cycle, ETS, fatty acid
synthesis, triacylglycerol synthesis,
lipolysis
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Metabolic Profile Kidney
Fuel(s) - major fuels glucose, fatty acids
Fuel use(s) - active transport, biosynthesis
(glucose)
Main metabolic pathways - Normal
conditions - glycolysis, fatty acid oxidation,
citric acid cycle, ETS During
starvation - gluconeogenesis
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Metabolic Profile Liver
Fuel(s) - major fuel fatty acids
Fuel use(s) - biosynthesis of glucose, fatty
acids, glycogen, triacylglycerols,
cholesterol, bile salts, proteins, urea
Main metabolic pathways - metabolic hub
Carbohydrate - incoming - glycolysis,
glycogenesis, lipogenesis, citric acid
cycle, ETS Low blood glucose -
glycogenolysis, gluconeogenesis
Lipid - incoming - fatty acid oxidation, citric
acid cycle, ETS, cholesterol synthesis,
ketone body synthesis Surplus fuel - fatty
acid and triacylglycerol synthesis
Amino acids - protein synthesis Synthesis
of nitrogenous compounds, glucose, urea
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Tissue Interrelationships Liver as Fuel Provider
for Other Tissues
Glucose provider - glycogenolysis,
gluconeogenesis
Fatty acid provider Excess fuel converted to
triacylglycerols then VLDLs Provide fatty
acids to other tissues or for storage in
adipose tissue
Ketone body provider Soluble form of fatty
acid fuel Produced when blood glucose level low
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Tissue Interrelationships Liver and Skeletal
Muscle
Cori Cycle
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Tissue Interrelationships Liver and Skeletal
Muscle
Alanine-Glucose Cycle
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Mechanism of Hormone Action Glucagon and
Epinephrine
adenylyl cyclase
hormone
hormone binds to receptor and stimulates adenylyl
cyclase
receptor
adenylyl cyclase catalyzes synthesis of
secondary messenger (cAMP)
Glucagon (liver)
glycogenesis ()
Inhibits glycogen synthase
glycogenolysis ()
Stimulates glycogen phosphorylase
glycolysis ()
Inhibits phosphofructokinase
gluconeogenesis ()
Stimulates fructose 1,6-phosphatase
Epinephrine (liver)
cAMP stimulates protein kinase to catalyze
phophorylation of key proteins
glycogenesis ()
Inhibits glycogen synthase
glycogenolysis ()
Stimulates glycogen phosphorylase
Glucagon and Epinephrine (adipose tissue)
glycolysis ()
Inhibits phosphofructokinase
gluconeogenesis ()
Stimulates fructose 1,6-phosphatase
Epinephrine (skeletal muscle)
Stimulates lipase
lipolysis ()
glycogenesis ()
Inhibits glycogen synthase
glycogenolysis ()
Stimulates glycogen phosphorylase
glycolysis ()
Stimulates phosphofructokinase
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Mechanism of Hormone Action Insulin
Insulin binds to receptor Stimulates synthesis
of secondary messenger (inositol triphosphate,
IP3 ) IP3 activates protein kinase that in turn
catalyzes phosphorylation of key enzymes
Processes and enzymes affected (take in and use
fuel)
Stimulates glucose uptake (liver, muscle, adipose
tissue)
Stimulates glycogen synthase (liver and muscle)
glycogenesis ()
Inhibits glycogen phosphorylase (liver and
muscle) glycogenolysis ()
Stimulates phosphofructokinase
glycolysis ()
Inhibits fructose 1,6-bisphophatase (liver)
gluconeogenesis ()
Stimulates fatty acid synthesis (liver)
lipogenesis ()
Inhibits hormone-sensitive lipase (adipose
cells) lipolysis ()
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Combined Effects of Insulin The well-fed state
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Combined Effects of Glucagon The fasting state
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Interplay between insulin and glucagon
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Normal Daily Cycle for Glycogen
100 g
75 g
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Starvation First Week
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Glucose Production by Liver and Kidney During
First 10 Days of Fasting
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Starvation Six Weeks
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Fuel Metabolism in Starvation
Amount formed or consumed in 24 hours (grams)
Fuel exchanges and consumption
3rd day
40th day
Fuel use by the brain
40
100
40
Fuel mobilization
180
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Fuel output of the liver
40
150
40
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Metabolic Adjustment by the Liver During
Prolonged Fasting or in Uncontrolled Diabetes