Summary of Metabolic Pathways
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
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
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, triacylglycerol
synthesis, lipolysis,
2
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
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
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
Tissue Interrelationships: Liver and
Skeletal Muscle
Alanine-Glucose
Cycle
Mechanism of Hormone Action: Glucagon and Epinephrine
adenylyl
cyclase
hormone
hormone binds to receptor and
stimulates adenylyl cyclase
receptor
ATP
Glucagon (liver)
Inhibits glycogen synthase
Stimulates glycogen phosphorylase
glycogenesis ( –)
glycogenolysis (+)
Inhibits phosphofructokinase
Stimulates fructose 1,6-phosphatase
glycolysis ( –)
gluconeogenesis (+)
Epinephrine (liver)
Inhibits glycogen synthase
Stimulates glycogen phosphorylase
glycogenesis ( –)
glycogenolysis (+)
Inhibits phosphofructokinase
Stimulates fructose 1,6-phosphatase
glycolysis ( –)
gluconeogenesis (+)
Epinephrine (skeletal muscle)
Inhibits glycogen synthase
Stimulates glycogen phosphorylase
glycogenesis ( –)
glycogenolysis (+)
Stimulates phosphofructokinase
glycolysis ( +)
cyclic
AMP
adenylyl cyclase catalyzes
synthesis of secondary
messenger (cAMP)
protein
kinase
phosphorylated
proteins
cAMP stimulates protein kinase to
catalyze phophorylation of key proteins
Glucagon and Epinephrine
(adipose tissue)
Stimulates lipase
lipolysis ( +)
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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
Inhibits fructose 1,6-bisphophatase (liver)
glycolysis (+)
gluconeogenesis (–)
Stimulates fatty acid synthesis (liver)
lipogenesis (+)
Inhibits hormone-sensitive lipase (adipose cells)
lipolysis (–)
Combined Effects of Insulin: The well-fed state
Combined Effects of Glucagon: The fasting state
5
Interplay between
insulin and glucagon
Normal Daily Cycle for Glycogen
100 g
75 g
Starvation: First Week
6
Glucose Production by Liver and Kidney
During First 10 Days of Fasting
Starvation: Six Weeks
Fuel Metabolism in Starvation
Fuel exchanges and consumption
Amount formed or consumed
in 24 hours (grams)
3rd day
40th day
Fuel use by the brain
Glucose
Ketone bodies
All other use of glucose
100
40
50
100
50
40
180
180
75
20
Fuel mobilization
Adipose-tissue lipolysis
Muscle-protein degradation
Fuel output of the liver
Glucose
120
40
Ketone bodies
150
150
30
40
Fuel output of the kidney
7
Metabolic Adjustment by the Liver During
Prolonged Fasting or in Uncontrolled Diabetes
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