Summary of Metabolic Pathways
Metabolic Profile: Brain
Fuel(s) - glucose is prime fuel uses ~120g/dayFuel use(s) - active transport (Na+, K+ ), biosynthesisGlucose 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 acidsHighly-active muscle - glucose from glycogen
produces lactateFuel use(s) - contraction, active transport (Ca2+)Main metabolic pathways - Resting muscle (aerobic)
fatty acid oxidation, citric acid cycle, ETSHighly-active muscle (anaerobic)
glycogenolysis, glycolysis
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, fatty acid synthesis, triacylglycerol synthesis, lipolysis
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: LiverFuel(s) - major fuel fatty acids
Fuel use(s) - biosynthesis of glucose, fatty acids, glycogen, triacylglycerols, cholesterol, bile salts, proteins, urea
Main metabolic pathways - metabolic hubCarbohydrate - 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 synthesisAmino 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
CoriCycle
Tissue Interrelationships: Liver and Skeletal Muscle
Alanine-Glucose Cycle
Tissue Interrelationships: Liver and Skeletal Muscle
Mechanism of Hormone Action: Glucagon and Epinephrine
receptor
hormoneadenylyl cyclase
ATPcyclicAMP
proteinkinasephosphorylated
proteins
hormone binds to receptor andstimulates adenylyl cyclase
adenylyl cyclase catalyzessynthesis of secondarymessenger (cAMP)
cAMP stimulates protein kinase to catalyze phophorylation of key proteins
Glucagon (liver)
Stimulates glycogen phosphorylase glycogenolysis (+)Inhibits glycogen synthase glycogenesis (–)
Stimulates fructose 1,6-phosphatase gluconeogenesis (+)
Inhibits phosphofructokinase glycolysis (–)
Epinephrine (liver)
Stimulates fructose 1,6-phosphatase gluconeogenesis (+)
Stimulates glycogen phosphorylase glycogenolysis (+)Inhibits glycogen synthase glycogenesis (–)
Inhibits phosphofructokinase glycolysis (–)
Epinephrine (skeletal muscle)
Stimulates glycogen phosphorylase glycogenolysis (+)Inhibits glycogen synthase glycogenesis (–)
Stimulates phosphofructokinase glycolysis (+)
Glucagon and Epinephrine (adipose tissue)
Stimulates lipase lipolysis (+)
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 enzymesProcesses and enzymes affected (take in and use fuel)
Stimulates glycogen synthase (liver and muscle) glycogenesis (+)
Inhibits glycogen phosphorylase (liver and muscle) glycogenolysis (–)
Stimulates glucose uptake (liver, muscle, adipose tissue)
Stimulates fatty acid synthesis (liver) lipogenesis (+)
Stimulates phosphofructokinase glycolysis (+)Inhibits fructose 1,6-bisphophatase (liver) gluconeogenesis (–)
Inhibits hormone-sensitive lipase (adipose cells) lipolysis (–)
Combined Effects of Insulin: The well-fed state
Combined Effects of Glucagon: The fasting state
Interplay betweeninsulin and glucagon
Normal Daily Cycle for Glycogen
75 g
100 g
Starvation: First Week
Glucose Production by Liver and KidneyDuring First 10 Days of Fasting
Starvation: Six Weeks
Fuel Metabolism in Starvation
Fuel exchanges and consumption
Amount formed or consumedin 24 hours (grams)
3rd day 40th day
Fuel use by the brain
Fuel output of the liver
Fuel mobilization
Muscle-protein degradation 75
180
40
100Ketone bodies 50
All other use of glucose 50
Glucose 100 40
Adipose-tissue lipolysis 180
20
150
Glucose 120
Ketone bodies 150
40
Fuel output of the kidney 30 40
Metabolic Adjustment by the Liver During Prolonged Fasting or in Uncontrolled Diabetes