1. Summary of Metabolic Pathways

2. 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

3. 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

5. 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

6. 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

7. 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

8. 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

9. 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

10. Tissue Interrelationships: Liver and Skeletal Muscle
Cori
Cycle

11. Tissue Interrelationships: Liver and Skeletal Muscle
Alanine-Glucose
Cycle

12. Glucagon and Epinephrine
Mechanism of Hormone Action: Glucagon and Epinephrine
adenylyl
cyclase
hormone
hormone binds to receptor and
stimulates adenylyl cyclase
ATP
cyclic
AMP
receptor
adenylyl cyclase catalyzes
synthesis of secondary
messenger (cAMP)
protein
kinase
phosphorylated
proteins
Glucagon (liver)
Inhibits glycogen synthase
glycogenesis (–)
Stimulates glycogen phosphorylase
glycogenolysis (+)
Inhibits phosphofructokinase
glycolysis (–)
Stimulates fructose 1,6-phosphatase
gluconeogenesis (+)
Epinephrine (liver)
cAMP stimulates protein kinase to
catalyze phophorylation of key proteins
Inhibits glycogen synthase
glycogenesis (–)
Stimulates glycogen phosphorylase
glycogenolysis (+)
Glucagon and Epinephrine
(adipose tissue)
Inhibits phosphofructokinase
glycolysis (–)
Stimulates fructose 1,6-phosphatase
gluconeogenesis (+)
Epinephrine (skeletal muscle)
Stimulates lipase
lipolysis (+)
Inhibits glycogen synthase
glycogenesis (–)
Stimulates glycogen phosphorylase
glycogenolysis (+)
Stimulates phosphofructokinase
glycolysis (+)

13. 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 (–)

14. Combined Effects of Insulin: The well-fed state

15. Combined Effects of Glucagon: The fasting state

16. Interplay between
insulin and glucagon

17. Normal Daily Cycle for Glycogen

18. Starvation: First Week

19. Glucose Production by Liver and Kidney During First 10 Days of Fasting

20. Starvation: Six Weeks

21. Amount formed or consumed
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
Glucose
100 40
Ketone bodies 50
100
All other use of glucose 50 40
Fuel mobilization
Adipose-tissue lipolysis
180
180
Muscle-protein degradation 75 20
Fuel output of the liver
Glucose
120 40
Ketone bodies
150
150
Fuel output of the kidney 30 40

22. Metabolic Adjustment by the Liver During Prolonged Fasting or in Uncontrolled Diabetes