Introduction to Metabolism
Joe vs. Josie
Jack Blazyk
Professor of Biochemistry
Associate Dean for Research & Grants
Major Dietary Fuel Molecules
Carbohydrates
Starch, Sucrose, Lactose
mostly Glucose
Lipids
Triglycerides
Contains 3 Fatty Acids
Proteins
Polymer of Amino Acids
Contain N in addition to C, H, O
Design of Metabolism
Activated Precursors
Macromolecules
UDP-Glucose
Fatty Acyl-CoA
Aminoacyl t-RNA
Glycogen
Triglycerides
Proteins
CHEMICAL
POWER
Anabolism
(Biosynthesis)
Precursors
Glucose
Fatty Acids
Amino Acids
40%
O2
Oxidation
(Combustion)
ENERGY
60%
HEAT
Catabolism
CO2
H2O
NH3
What is essential in our diet?
Proteins
Amino acids
Lipids
Unsaturated fatty acids
Carbohydrates
Glucose ??
How do we store our energy reserves?
Glycogen
Liver
Muscle
Triglycerides
Adipose
Where?
Carbohydrates <1%
e.g., Glucose
Lipids
e.g., Fatty Acids
Proteins
Amino acids
85%
15%
Design of Metabolism
Activated Precursors
Macromolecules
UDP-Glucose
Fatty Acyl-CoA
Aminoacyl t-RNA
Glycogen
Triglycerides
Proteins
CHEMICAL
POWER
Anabolism
(Biosynthesis)
Precursors
Glucose
Fatty Acids
Amino Acids
40%
O2
Oxidation
(Combustion)
ENERGY
60%
HEAT
Catabolism
CO2
H2O
NH3
O
CH3 - C - S - CoA
HS - CoA
3 H2O
Located in
mitochondrial
matrix
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
Why are lipids our primary
energy reserves?
Carbohydrates
4 Cal/g
e.g., Glucose
C6H12O6
9 Cal/g
Lipids
e.g., Palmitic Acid
C16H32O2
Proteins
4 Cal/g
e.g., Glycine
C2H5O2N
More Reduced
Joe
16 yo, 5’10” tall, 160 pounds
Joe eats 4000+ calories per day
After 6 months, Joe weighs 210 pounds
Joe drinks 6 to 8 20-ounce Cokes per day
Previous Nutrition Label
1440 - 1920 Cal/day
Body Mass Index
Joe
5’10”
Initial BMI
160 lbs.
23.0
Final BMI
210 lbs.
30.1
What is happening
in Joe’s liver?
What is its metabolic
response to feasting?
Glycolysis
Glycogenesis
Well-Fed
Liver
Pentose
Shunt
Triglyceride
Synthesis
Fatty Acid
Synthesis
What is happening in Joe’s
adipose tissue?
What is its metabolic response
to feasting?
Glycolysis
Pentose
Shunt
Cholesterol
Synthesis
Triglyceride
Synthesis
Well-Fed
Adipose
Fatty Acid
Synthesis
What is happening in Joe’s
skeletal muscle?
What is its metabolic response
to feasting?
Glycogenesis
Well-Fed
Muscle
Josie
16 yo, 5’6” tall, 130 pounds
Josie eats < 600 calories per day
After 6 months, Josie weighs 105 pounds
Pria Power Bars Chocolate Peanut Crunch
Serving Size: 1 Bar = 28g
Calories
Calories From
Fat
110
30
Amount/Serving
Total Fat
Saturated Fat
Trans Fat
Sodium
Total Carb
Dietary Fiber
Sugars
Protein
% DV*
3.5g
2g
0g
85mg
16g
1g
10g
5g
5%
10%
4%
5%
4%
10%
Josie
5’6”
Initial BMI
130 lbs.
21.0
Final BMI
105 lbs.
16.9
What is happening in
Josie’s liver?
What is its metabolic response to
fasting?
Fasting
Liver
Gluconeogenesis
Glycogenolysis
Ketone Body
Synthesis
Fatty Acid
Oxidation
What is happening in
Josie’s adipose tissue?
What is its metabolic response
to fasting?
No Uptake
Fasting
Adipose
Triglyceride
Breakdown
Fatty Acid
Oxidation
What is happening in
Josie’s skeletal muscle?
What is its metabolic response
to fasting?
No Uptake
Fasting
Muscle
Ketone Body
Utilization
Fatty Acid
Oxidation
Fasting
Liver
Gluconeogenesis
Glycogenolysis
Ketone Body
Synthesis
Fatty Acid
Oxidation
Why does Josie’s liver
make ketone bodies?
Aren’t ketone bodies
bad?
Palmitic Acid
CH3-(CH2)14-COOH
vs.
Acetoacetate
=
CH3 – C – CH2 – COOH
OH
_
O
b-Hydroxybutyrate
CH3 – CH – CH2 – COOH
Acetoacetate
=
O
CH3 – C – CH2 – COOH
Acetone
=
O
CH3 – C – CH3
+ CO2
Well-Fed State
Brain
Pancreas
Gut
Insulin
Glycogen
Glucose
aa
Portal
Vein
CO2 + H2O
Glucose
aa
Liver
Urea
Adipose
CO2 + H2O
Protein
Chylomicrons
Pyruvate
TG
TG
Lymphatics
VLDL
CO2 + H2O
Lactate
Glycogen
Muscle
Lactate
RBC
Early Fasting State
Brain
Pancreas
Gut
Glucagon
Glycogen
Portal
Vein
CO2 + H2O
Glucose
Adipose
Liver
FA
Pyruvate
FA
CO2 + H2O
CO2 + H2O
Lymphatics
Lactate
Muscle
Lactate
RBC
Extended Fasting State
Brain
Pancreas
Gut
Glucagon
CO2 + H2O
Glucose
Portal
Vein
KB
Urea
Glycerol
FA
Liver
Pyruvate
Adipose
FA
CO2 + H2O
CO2 + H2O
Lymphatics
aa
Protein
Lactate
Cortisol
RBC
Muscle
=
O
CH3 – C – CH2 – COOH
Acidosis
CH3 – C – CH2 – COO pH
OH
_
_
CH3 – CH – CH2 – COOH
H
O
b-Hydroxybutyrate
OH
+
=
Acetoacetate
CH3 – CH – CH2 – COO-
+
H
Compensation
+
HCO3- + H
H2CO3
H2O + CO2
Respiration
pH
Fig. 16-10
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 6phosphatase, 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
Those for synthesis and catabolism
neurotransmitter metabolism 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 Free fatty acids, glycerol
VLDL triacylglycerol
Lipoprotein lipase, hormonesensitive lipase, enzymes of
pentose phosphate pathway
Fast twitch
muscle
Glycolysis
Glucose, glycogen
Lactate, (alanine and
ketoacids in fasting)
—
Ketone bodies,
chylomicron and VLDL
triacylglycerol
—
Lipoprotein lipase, very active
electron transport chain
Free fatty acids, lactate,
glycerol, glucose
Glucose
Glycerol kinase,
phosphoenolpyruvate
carboxykinase
Glucose
Lactate
Hemoglobin, enzymes of pentose
phosphate pathway
Slow twitch
muscle
Kidney
-Oxidation and citric acid cycle
Gluconeogenesis
Erythrocytes Anaerobic glycolysis, pentose phosphate
pathway
Harper's Illustrated Biochemistry, 28e
Abbreviation: VLDL, very low density lipoproteins.
Robert K. Murray, David A Bender, Kathleen M. Botham,
Peter J. Kennelly, Victor W. Rodwell, P. Anthony Weil