introduction to metabolism joe vs. josie jack blazyk professor of biochemistry associate dean for...
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Introduction to Metabolism
Joe vs. Josie
Jack BlazykProfessor of Biochemistry
Associate Dean for Research & Grants
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Major Dietary Fuel Molecules
CarbohydratesStarch, Sucrose, Lactose
mostly Glucose
LipidsTriglycerides
Contains 3 Fatty Acids
ProteinsPolymer of Amino Acids
Contain N in addition to C, H, O
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Design of MetabolismActivated Precursors Macromolecules
Precursors
GlycogenTriglycerides
Proteins
UDP-GlucoseFatty Acyl-CoA
Aminoacyl t-RNA
GlucoseFatty AcidsAmino Acids
CHEMI CALPOWER
O2
ENERGY
CO2
H2O
NH3
HEAT
60%
40%
Oxidation(Combustion)
Anabolism(Biosynthesis)
Catabolism
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What is essential in our diet?
Lipids
ProteinsAmino acids
Unsaturated fatty acids
CarbohydratesGlucose ??
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How do we store our energy reserves?
Carbohydratese.g., Glucose
Lipidse.g., Fatty Acids
ProteinsAmino acids
85%
15%
<1%GlycogenLiver
Muscle
TriglyceridesAdipose
Where?
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Design of MetabolismActivated Precursors Macromolecules
Precursors
GlycogenTriglycerides
Proteins
UDP-GlucoseFatty Acyl-CoA
Aminoacyl t-RNA
GlucoseFatty AcidsAmino Acids
CHEMI CALPOWER
O2
ENERGY
CO2
H2O
NH3
HEAT
60%
40%
Oxidation(Combustion)
Anabolism(Biosynthesis)
Catabolism
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Located in mitochondrial
matrix3 H2O
CH3 - C -
O
=
S - CoA HS - CoA
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Why are lipids our primary energy reserves?
1 gram of carbohydrate = 4 Cal/g
1 gram of protein = 4 Cal/g
1 gram of fat = 9 Cal/g
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Why are lipids our primary energy reserves?
Carbohydratese.g., Glucose
C6H12O6
Lipidse.g., Palmitic Acid
C16H32O2
Proteinse.g., Glycine
More Reduced
4 Cal/g
4 Cal/g
9 Cal/g
C2H5O2N
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Joe
16 yo, 5’10” tall, 160 pounds
Joe eats 4000+ calories per day
After 6 months, Joe weighs 210 pounds
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Joe drinks 6 to 8 20-ounce Cokes per day
1440 - 1920 Cal/day
Previous Nutrition Label
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Body Mass Index
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Joe
Initial BMI23.0
Final BMI30.1
5’10”
160 lbs.
210 lbs.
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What is happening in Joe’s liver?
What is its metabolic response to feasting?
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Gly
coly
sis
Glycogenesis
PentoseShunt
Fatty AcidSynthesis
TriglycerideSynthesis
Well-Fed Liver
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What is happening in Joe’s adipose tissue?
What is its metabolic responseto feasting?
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Gly
coly
sis Pentose
Shunt
Fatty AcidSynthesis
CholesterolSynthesis
TriglycerideSynthesis
Well-Fed Adipose
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What is happening in Joe’s skeletal muscle?
What is its metabolic responseto feasting?
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Well-Fed Muscle
Glycogenesis
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Josie
16 yo, 5’6” tall, 130 pounds
Josie eats < 600 calories per day
After 6 months, Josie weighs 105 pounds
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Pria Power Bars Chocolate Peanut Crunch
Serving Size: 1 Bar = 28g
Calories 110Calories From Fat 30
Amount/Serving % DV*
Total Fat 3.5g 5% Saturated Fat 2g 10% Trans Fat 0gSodium 85mg 4%Total Carb 16g 5% Dietary Fiber 1g 4% Sugars 10gProtein 5g 10%
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Josie
Initial BMI21.0
Final BMI16.9
5’6”
130 lbs.
105 lbs.
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What is happening in Josie’s liver?
What is its metabolic response to fasting?
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Fasting Liver
Glu
con
eog
enes
is
Fatty AcidOxidation
Ketone Body Synthesis
Glycogenolysis
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What is happening in Josie’s adipose tissue?
What is its metabolic responseto fasting?
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Fasting Adipose
Fatty AcidOxidation
TriglycerideBreakdown
No Uptake
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What is happening in Josie’s skeletal muscle?
What is its metabolic responseto fasting?
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Fasting Muscle Fatty Acid
Oxidation
Ketone BodyUtilization
No Uptake
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Fasting Liver
Glu
con
eog
enes
is
Fatty AcidOxidation
Ketone Body Synthesis
Glycogenolysis
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Why does Josie’s liver make ketone bodies?
Aren’t ketone bodies bad?
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CH3-(CH2)14-COOH
Palmitic Acid
CH3 – C – CH2 – COOH
O
=
_OH
CH3 – CH – CH2 – COOH
Acetoacetate b-Hydroxybutyrate
vs.
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CH3 – C – CH2 – COOH
O
=
Acetoacetate
CH3 – C – CH3
O=
Acetone
+ CO2
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Insulin
RBC
Liver
Muscle
Adipose
Brain
Gut
Portal Vein
Lymphatics
Glucose
Glycogen
Glucose
CO2 + H2O
aa
Protein
TG
Urea
Pancreas
Glucoseaa
TG
Pyruvate
Lactate
Lactate
Chylomicrons
VLDL
Glycogen
CO2 + H2O
CO2 + H2O
Well-Fed State
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Glucagon
RBC
Liver
Muscle
Adipose
Brain
Gut
Portal Vein
Lymphatics
Glycogen
Glucose
Glu
cose
CO2 + H2O
Pancreas
Pyruvate
CO2 + H2O
Early Fasting State
CO2 + H2O
FA
FA
Lactate
Lactate
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Glucagon
RBC
Liver
Muscle
Adipose
Brain
Gut
Portal Vein
Lymphatics
CO2 + H2O
Pancreas
Pyruvate CO2 + H2O
Extended Fasting State
KB
Lactate
FA
Glycerol
FA
CO2 + H2O
Protein
aa
Cortisol
Glucose
Urea
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CH3 – C – CH2 – COOH
O=
_OH
CH3 – CH – CH2 – COOH
Acetoacetate
b-Hydroxybutyrate_OH
CH3 – CH – CH2 – COO
CH3 – C – CH2 – COO
O
= -
-
H+
H+
pH
Acidosis
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HCO3- H+
pH
+ H2CO3 H2O + CO2
Respiration
Compensation
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Fig. 16-10
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Table 16–3. Summary of the Major Metabolic Features of the Principal Organs
Organ Major Pathways Main Substrates Major Products Exported Specialist Enzymes
Liver Glycolysis, gluconeogenesis, lipogenesis, -oxidation, citric acid cycle, ketogenesis, lipoprotein metabolism, drug metabolism, synthesis of bile salts, urea, uric acid, cholesterol, plasma proteins
Free fatty acids, glucose (in fed state), lactate, glycerol, fructose, amino acids, alcohol
Glucose, triacylglycerol in VLDL, ketone bodies, urea, uric acid, bile salts, cholesterol, plasma proteins
Glucokinase, glucose 6-phosphatase, glycerol kinase, phosphoenolpyruvate carboxykinase, fructokinase, arginase, HMG CoA synthase, HMG CoA lyase, alcohol dehydrogenase
Brain Glycolysis, citric acid cycle, amino acid metabolism, neurotransmitter synthesis
Glucose, amino acids, ketone bodies in prolonged starvation
Lactate, end products of neurotransmitter metabolism
Those for synthesis and catabolism of neurotransmitters
Heart -Oxidation and citric acid cycle Ketone bodies, free fatty acids, lactate, chylomicron and VLDL triacylglycerol, some glucose
— Lipoprotein lipase, very active electron transport chain
Adipose tissue
Lipogenesis, esterification of fatty acids, lipolysis (in fasting)
Glucose, chylomicron and VLDL triacylglycerol
Free fatty acids, glycerol Lipoprotein lipase, hormone-sensitive lipase, enzymes of pentose phosphate pathway
Fast twitch muscle
Glycolysis Glucose, glycogen Lactate, (alanine and ketoacids in fasting)
—
Slow twitch muscle
-Oxidation and citric acid cycle Ketone bodies, chylomicron and VLDL triacylglycerol
— Lipoprotein lipase, very active electron transport chain
Kidney Gluconeogenesis Free fatty acids, lactate, glycerol, glucose
Glucose Glycerol kinase, phosphoenolpyruvate carboxykinase
Erythrocytes Anaerobic glycolysis, pentose phosphate pathway
Glucose Lactate Hemoglobin, enzymes of pentose phosphate pathway
Abbreviation: VLDL, very low density lipoproteins.
Harper's Illustrated Biochemistry, 28e Robert K. Murray, David A Bender, Kathleen M. Botham, Peter J. Kennelly, Victor W. Rodwell, P. Anthony Weil