Introduction to Metabolism

Joe vs. Josie

Jack BlazykProfessor of Biochemistry

Associate Dean for Research & Grants

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

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

What is essential in our diet?

Lipids

ProteinsAmino acids

Unsaturated fatty acids

CarbohydratesGlucose ??

How do we store our energy reserves?

Carbohydratese.g., Glucose

Lipidse.g., Fatty Acids

ProteinsAmino acids

85%

15%

<1%GlycogenLiver

Muscle

TriglyceridesAdipose

Where?

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

Located in mitochondrial

matrix3 H2O

CH3 - C -

O

=

S - CoA HS - CoA

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?

Carbohydratese.g., Glucose

C6H12O6

Lipidse.g., Palmitic Acid

C16H32O2

Proteinse.g., Glycine

More Reduced

4 Cal/g

4 Cal/g

9 Cal/g

C2H5O2N

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

1440 - 1920 Cal/day

Previous Nutrition Label

Body Mass Index

Joe

Initial BMI23.0

Final BMI30.1

5’10”

160 lbs.

210 lbs.

What is happening in Joe’s liver?

What is its metabolic response to feasting?

Gly

coly

sis

Glycogenesis

PentoseShunt

Fatty AcidSynthesis

TriglycerideSynthesis

Well-Fed Liver

What is happening in Joe’s adipose tissue?

What is its metabolic responseto feasting?

Gly

coly

sis Pentose

Shunt

Fatty AcidSynthesis

CholesterolSynthesis

TriglycerideSynthesis

Well-Fed Adipose

What is happening in Joe’s skeletal muscle?

What is its metabolic responseto feasting?

Well-Fed Muscle

Glycogenesis

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 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%

Josie

Initial BMI21.0

Final BMI16.9

5’6”

130 lbs.

105 lbs.

What is happening in Josie’s liver?

What is its metabolic response to fasting?

Fasting Liver

Glu

con

eog

enes

is

Fatty AcidOxidation

Ketone Body Synthesis

Glycogenolysis

What is happening in Josie’s adipose tissue?

What is its metabolic responseto fasting?

Fasting Adipose

Fatty AcidOxidation

TriglycerideBreakdown

No Uptake

What is happening in Josie’s skeletal muscle?

What is its metabolic responseto fasting?

Fasting Muscle Fatty Acid

Oxidation

Ketone BodyUtilization

No Uptake

Fasting Liver

Glu

con

eog

enes

is

Fatty AcidOxidation

Ketone Body Synthesis

Glycogenolysis

Why does Josie’s liver make ketone bodies?

Aren’t ketone bodies bad?

CH3-(CH2)14-COOH

Palmitic Acid

CH3 – C – CH2 – COOH

O

=

_OH

CH3 – CH – CH2 – COOH

Acetoacetate b-Hydroxybutyrate

vs.

CH3 – C – CH2 – COOH

O

=

Acetoacetate

CH3 – C – CH3

O=

Acetone

+ CO2

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

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

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

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

HCO3- H+

pH

+ H2CO3 H2O + CO2

Respiration

Compensation

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 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