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Energy metabolism
(overview)
The flow of electrons provide
energy for organisms.
 All living organisms drive their energy,
directly or indirectly from radiant
energy of sunlight.
Photosynthetic cells
 Absorb light energy and
use it to drive electrons
from water to carbon
dioxide, forming
energy-rich carbon
skeletons, like starch,
glucose. Sucrose and
releasing of oxygen into
the atmosphere
6CO2 + 6H2O C6H12O6 + 6O2
24 e sunlight
atmospheric
Non-photosynthetic
cells
 Obtain the energy they need by oxidizing the
energy rich carbon skeleton products of
photosynthesis driving electrons to
atmospheric oxygen to form water and
carbon dioxide and other rich energy
products
C6H12O6 + 6O2 6CO2 + 6H2O + Energy
24e
atmospheric
-C-C-C-
-4e; -4H+
O2
-4e; -4H+
-4e; -4H+
-4e; -4H+
Liberating Energy
Carriers
for electrons & H+
Carriers
for electrons & H+
Carriers
for electrons & H+
2H2O
High
energy
compound
Low energy
compound
Energy
40 - 45% 55- 60%
phosphorylation of ADP
ADP + Pi
ATP
heat production
(thermogenesis)
+ 7.3 Kcal/mol
Liberated
Sources of energy
Energy sources
Exogenous Endogenous
carbon skeleton
of the food
OXIDATION
de novo synthesized
carbon skeleton
OXIDATION
Energy content of fuels:
 Carbohydrates -
 4 Kcal/g
 Protein - 4 Kcal/g
 Alcohol - 7 Kcal/g
 Fats – 9 Kcal/g
Nutritional states
1. Well-fed State –immediately after meal
( 1-8 hr)
2. Overnight fasting – 8-12 hr after last
meal
3. Fasting – 13hr – 48 hr
4. Starvation – prolonged fasting – 2-40
days
Major carbon skeletons oxidation during well-fed & fasting in different organs
Organ Well-Fed Fasting
Liver
Cardiac
muscles
Glucose &
amino acids
Fatty
acids
Fatty acids
Fatty acids,
ketone bodies
Muscles Glucose
Glycogen, Fatty
acids, Ketone bodies
Adipose
tissue
Glucose Fatty acids
Brain Glucose
Glucose
(limit ketone bodies)
RBCs Glucose Glucose
ATP production in various conditions
At Rest High-intensive
exercise
Prolonged
work and exercise
70%
from
fat
from
carbo-
from
carbo-
from
fat
100% 100%30%
The central role of ATP in metabolism
Stored molecules
Ingested food
Solar photons
CATABOLIC
REACTIONS
ANABOLIC
REACTIONS
Osmotic and
electrical work
Mechanical work
Chemical synthesis
Transferance of
genetic information
Other cellular work
ADP
ATP
CO2
NH3
H2O
Simple products
precursors
ATP
structure
ATP hydrolysis
 Energy liberates during ATP hydrolysis
 But during hydrolysis of ester bond small amount
of energy is liberated and this reaction doesn’t use
as a source of energy in the body.
ATP ADP + Pi + 7.2 Kcal/mole
ATP AMP + PPi + 10 Kcal/mole
PPi
2 Pi + 7.0 Kcal/mole
ATP Adenine + PPPi + 1.3 Kcal/mole
Synthesis of ATPs
Pathways of ATPs synthesis
Phosphorylation
of ADP
Substrate-level
phosphorylation
Oxidative
phosphorylation
De novo synthesis
of AMP (liver)
salvage pathway
in all nucleated
cells
DNA,RNA
AMP + ATP
2 ADP
Adenylayl
kinase
Adenylyl kinase reaction
 When ATP becomes
depleted (low energy
status) AMP increases
in concentration and
acts as signal to
increase the rate of
catabolic reactions
which generate more
ATPs.
ATP AMP Anabolism ATP
direction of regulation
cell
ATP AMP ATP
direction of regulation
cell
Catabolism
Substrate level phosphorylation
(enzyme kinase): cytosolic & mito-
processes
 Hydrolysis of some organophosphates:
 Creatine-P ( 10.3 Kcal/mol)
 Phosphoenolpyruvate (14.8 Kcal/mol)
 1,3-Bisphosphoglycerate (11.8 Kcal/mol)
Example of substrate-level
phosphorylation: ATP-PC system
 Creatine-P is the
primary source of
ATP for short – term
(8-10 sec), high-
intensity exercise
such as sprinting or
jumping.
Oxidative phosphorylation of
ADP (mitochondrial process
only)
 Requires:
 1. Oxygen
 2. High mitochondria content
 3. ATP synthase
 4. Oxidation of NADH or
FADH2 (donors of electrons &
H+)
 5. ATP synthesis is coupled
with reducing of oxygen and
oxidation of NADH and FADH2
Stages of energy
liberation
 Nobel prize for Medicine in 1978
Fritz Lipmann "for his discovery of co-enzyme A
and its importance for intermediary metabolism"
Hans Krebs "for his discovery of the
citric acid cycle".
Nobel prize for Medicine, 1953
Peter Mitchell “ for his discovery of the electron
transport chain and chemiosmotic theory
of ATP production”
DIETARY
Polysaccharides Proteins Lipids
Monosaccharides Amino acids Fatty acids
GLUCOSE
De novo
synthesis
De novo
synthesis
Pyruvate
mito-
ATPs
Acetyl CoA
I phase
II phase
III phase
TCA
2CO2
IV phase
3NADH; FADH2
ETC
O2
H2O
ATP-ase
ADP
ATP
Pi
electrons flow
V phase
Sources of energy
during muscle exercises
ATP-glycolytic pathway
(1-3 min)
ANAEROBIC GLYCOLYSIS
MUSCLE GLYCOGEN
n GLUCOSE - 6-P
2n LACTATE
2n ATP
LIVER
(accumulation)
PAIN
Aerobic respiration (OXPHOS)
(after 3 min)
 Increase lungs
respiration &
increase blood
circulation
Glycogen Lactate Fat
Glucose-6-P
Pyruvate
Acetyl CoA
after 2 hr
OXPHOS n ATP
RECOMMENDED REFERENCES:
1. “Medical Biochemistry” MN Chatterjea Rana Shinde 2005, sixth edition.
2. “Lippincott’s Illustrated Reviews: Biochemistry” Richard A. Harwey Pamela C. Champe, Ph.D, 2nd
edition.
3. “Fundamentals of Biochemistry” Dr. A.C. Deb. 2008.
4. “Biochemistry” U. Satyanarayana, U. Chakrapani. 2005.
ADDITIONAL REFERENCES:
1. Textbook of biochemistry for medical students. DM Vasudevan, Sreekumari S, Kannan
Vaidyanathan.- Sixth Edition: Kochi, Kerala.-2011.
2. Marks’ Basic Medical Biochemistry: A Clinical Approach, 2nd Edition.
3. Essentials of biochemistry Pankaja Naik PhD.- 2012, First Edition.

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Energy Metabolism

  • 2. The flow of electrons provide energy for organisms.  All living organisms drive their energy, directly or indirectly from radiant energy of sunlight.
  • 3. Photosynthetic cells  Absorb light energy and use it to drive electrons from water to carbon dioxide, forming energy-rich carbon skeletons, like starch, glucose. Sucrose and releasing of oxygen into the atmosphere 6CO2 + 6H2O C6H12O6 + 6O2 24 e sunlight atmospheric
  • 4. Non-photosynthetic cells  Obtain the energy they need by oxidizing the energy rich carbon skeleton products of photosynthesis driving electrons to atmospheric oxygen to form water and carbon dioxide and other rich energy products C6H12O6 + 6O2 6CO2 + 6H2O + Energy 24e atmospheric
  • 5. -C-C-C- -4e; -4H+ O2 -4e; -4H+ -4e; -4H+ -4e; -4H+ Liberating Energy Carriers for electrons & H+ Carriers for electrons & H+ Carriers for electrons & H+ 2H2O High energy compound Low energy compound
  • 6. Energy 40 - 45% 55- 60% phosphorylation of ADP ADP + Pi ATP heat production (thermogenesis) + 7.3 Kcal/mol Liberated
  • 7. Sources of energy Energy sources Exogenous Endogenous carbon skeleton of the food OXIDATION de novo synthesized carbon skeleton OXIDATION
  • 8. Energy content of fuels:  Carbohydrates -  4 Kcal/g  Protein - 4 Kcal/g  Alcohol - 7 Kcal/g  Fats – 9 Kcal/g
  • 9. Nutritional states 1. Well-fed State –immediately after meal ( 1-8 hr) 2. Overnight fasting – 8-12 hr after last meal 3. Fasting – 13hr – 48 hr 4. Starvation – prolonged fasting – 2-40 days
  • 10. Major carbon skeletons oxidation during well-fed & fasting in different organs Organ Well-Fed Fasting Liver Cardiac muscles Glucose & amino acids Fatty acids Fatty acids Fatty acids, ketone bodies Muscles Glucose Glycogen, Fatty acids, Ketone bodies Adipose tissue Glucose Fatty acids Brain Glucose Glucose (limit ketone bodies) RBCs Glucose Glucose
  • 11. ATP production in various conditions At Rest High-intensive exercise Prolonged work and exercise 70% from fat from carbo- from carbo- from fat 100% 100%30%
  • 12. The central role of ATP in metabolism Stored molecules Ingested food Solar photons CATABOLIC REACTIONS ANABOLIC REACTIONS Osmotic and electrical work Mechanical work Chemical synthesis Transferance of genetic information Other cellular work ADP ATP CO2 NH3 H2O Simple products precursors
  • 14. ATP hydrolysis  Energy liberates during ATP hydrolysis  But during hydrolysis of ester bond small amount of energy is liberated and this reaction doesn’t use as a source of energy in the body. ATP ADP + Pi + 7.2 Kcal/mole ATP AMP + PPi + 10 Kcal/mole PPi 2 Pi + 7.0 Kcal/mole ATP Adenine + PPPi + 1.3 Kcal/mole
  • 16. Pathways of ATPs synthesis Phosphorylation of ADP Substrate-level phosphorylation Oxidative phosphorylation De novo synthesis of AMP (liver) salvage pathway in all nucleated cells DNA,RNA AMP + ATP 2 ADP Adenylayl kinase
  • 17. Adenylyl kinase reaction  When ATP becomes depleted (low energy status) AMP increases in concentration and acts as signal to increase the rate of catabolic reactions which generate more ATPs. ATP AMP Anabolism ATP direction of regulation cell ATP AMP ATP direction of regulation cell Catabolism
  • 18. Substrate level phosphorylation (enzyme kinase): cytosolic & mito- processes  Hydrolysis of some organophosphates:  Creatine-P ( 10.3 Kcal/mol)  Phosphoenolpyruvate (14.8 Kcal/mol)  1,3-Bisphosphoglycerate (11.8 Kcal/mol)
  • 19. Example of substrate-level phosphorylation: ATP-PC system  Creatine-P is the primary source of ATP for short – term (8-10 sec), high- intensity exercise such as sprinting or jumping.
  • 20. Oxidative phosphorylation of ADP (mitochondrial process only)  Requires:  1. Oxygen  2. High mitochondria content  3. ATP synthase  4. Oxidation of NADH or FADH2 (donors of electrons & H+)  5. ATP synthesis is coupled with reducing of oxygen and oxidation of NADH and FADH2
  • 22.  Nobel prize for Medicine in 1978 Fritz Lipmann "for his discovery of co-enzyme A and its importance for intermediary metabolism" Hans Krebs "for his discovery of the citric acid cycle". Nobel prize for Medicine, 1953 Peter Mitchell “ for his discovery of the electron transport chain and chemiosmotic theory of ATP production”
  • 23. DIETARY Polysaccharides Proteins Lipids Monosaccharides Amino acids Fatty acids GLUCOSE De novo synthesis De novo synthesis Pyruvate mito- ATPs Acetyl CoA I phase II phase III phase TCA 2CO2 IV phase 3NADH; FADH2 ETC O2 H2O ATP-ase ADP ATP Pi electrons flow V phase
  • 24. Sources of energy during muscle exercises
  • 25.
  • 26. ATP-glycolytic pathway (1-3 min) ANAEROBIC GLYCOLYSIS MUSCLE GLYCOGEN n GLUCOSE - 6-P 2n LACTATE 2n ATP LIVER (accumulation) PAIN
  • 27. Aerobic respiration (OXPHOS) (after 3 min)  Increase lungs respiration & increase blood circulation Glycogen Lactate Fat Glucose-6-P Pyruvate Acetyl CoA after 2 hr OXPHOS n ATP
  • 28. RECOMMENDED REFERENCES: 1. “Medical Biochemistry” MN Chatterjea Rana Shinde 2005, sixth edition. 2. “Lippincott’s Illustrated Reviews: Biochemistry” Richard A. Harwey Pamela C. Champe, Ph.D, 2nd edition. 3. “Fundamentals of Biochemistry” Dr. A.C. Deb. 2008. 4. “Biochemistry” U. Satyanarayana, U. Chakrapani. 2005. ADDITIONAL REFERENCES: 1. Textbook of biochemistry for medical students. DM Vasudevan, Sreekumari S, Kannan Vaidyanathan.- Sixth Edition: Kochi, Kerala.-2011. 2. Marks’ Basic Medical Biochemistry: A Clinical Approach, 2nd Edition. 3. Essentials of biochemistry Pankaja Naik PhD.- 2012, First Edition.