Introduction to metabolism following the curriculum of medical biochemistry of MBBS course

1. INTRODUCTION
TO METABOLISM
Dr. Farhana Atia
Associate Professor
Department of Biochemistry
Nilphamari Medical College, Nilphamari

2. Metabolism
• Metabolism is the term refers to all chemical reactions
that occur in the living cells catalyzed by enzymes,
coenzymes, cofactors & regulated by hormones,
vitamins
 Aim
• Release energy from ingested food
• Transformation of small organic compound into
macromolecule

3. Pathways of Metabolism
Pathways of metabolism-
1. Anabolic pathways
2. Catabolic pathways
3. Amphibolic pathways

4. Anabolism
Involves in the
• biosynthesis of larger and
more complex molecules
• from smaller precursors &
• requires expenditure of
energy
either in the form of
ATP or
using reducing
equivalents storing
NADH/ NADPH
Involves in the
• breakdown of larger molecules
like glucose, amino acid, FA &
• form CO₂, H₂O, NH₃ & energy.
• commonly involving oxidative
reactions;
• they are exothermic, producing
reducing equivalents and
ATP(mainly via the respiratory
chain).
Catabolism

5. Amphibolic pathway
• occur at the ‘crossroads’ of metabolism, acting as links
between the anabolic and catabolic pathways
• can be either anabolic or catabolic, depending on the
energy conditions in the cell

6. Conversion
of food
energy to
ATP

7. Bioenergetics
• Study of energy changes associated with biochemical reaction.
• Free energy [G]: Energy available to do work.
• Standard free energy change [∆G⁰]
• Exergonic/energy yielding reaction
• catabolism
• reaction proceed spontaneously with loss of free energy [∆G
negative]
• Endergonic/energy requiring reaction
• reaction proceed only if free energy is gained [∆G negative]
• Coupled with exergonic reaction

8. Transfer of energy
• Biological system use chemical energy to maintain
living process
• Free energy is obtained by breakdown of complex
organic molecules
• Much of liberated energy is not used directly by the cell
• But there is a formation of bond between phosphoric
acid residue & certain organic compounds
• Different amount of energy is released on hydrolysis of
the bond

9. ATP
• ATP plays a central role in transfer of free energy
• The standard free energy [∆G⁰] on hydrolysis of terminal
phosphate of ATP is -7.3 kcal/mol
• This value divides the biochemically important phosphates
into 2 groups
1. Low energy phosphates: have G⁰ value smaller than
that of ATP.
2. High energy phosphates: G⁰ value is higher than that of
ATP. It include ATP.

10. High & Low Energy Phosphate Compounds
Compound ∆G⁰ (Kcal/mol)
Phosphoenolpyruvate -14.8
Carbamoyl phosphate -12.3
1,3-Bisphosphoglycerate -11.8
Creatine phosphate -10.3
ATPAMP+PPi -7.7
ATPADP+Pi -7.3
Glucose-1-phosphate -5.0
PPi -4.6
Fructose-6-phosphate -3.8
Glucose-6-phosphate -3.3
Glycerol-3-phosphate -2.2

11. ATP: Energy carrier
• ATP is able to act as a donor
of high energy phosphate [~P ]
to form low energy phosphate
compounds
• Likewise, ADP can accept ~P
to form ATP
• Thus ATP/ADP cycle connects
those process that generate
~P to those processes that
utilize ~P

12. Biologic oxidation
• Oxidation [removal of electron or H] of biomolecules
within biologic system
• Oxidation is always accompanied by reduction of an
electron acceptor
• Can take place without participation of molecular
oxygen [dehydrogenation]

13. Oxydoreductase
Oxidases
Dehydrogenase
Hydroperoxidase
oxygenase

14. Redox potential
It is the numerical expression of free energy change during
oxidation-reduction.
It is the tendency of any redox pair to lose or gain electron
[quantitatively expressed as E0 with unit in volt]
More negative RP tendency to lose electron
More positive RP tendency to accept electron
H⁺/H₂ -0.42v
NAD⁺/NADH -0.32v
FMN/FMNH₂ -0.22v

15. Respiratory Chain
• Highly organized chain of enzyme & coenzyme in
mitochondria
• Arranged in order of increasing redox potential
• Collect & transport reducing equivalents (H/electron)

16. Respiratory Chain
• In respiratory chain biomolecule become oxidized &
coenzyme reduced
• Reduced coenzyme then deliver 2H to RC through which H
propagate, sequentially reduce & oxidize every component
of chain
• finally get condensed with molecular oxygen to form H₂O,
and the liberated free energy is trapped as ATP (in the
machinery for oxidative phosphorylation).

17. Respiratory Chain

18. Component of respiratory chain
Four large protein complexes embedded in inner mitochondrial
membrane
1. Complex I : NADH-Q oxidoreductase
2. Complex III : Q-cytochrome c oxidoreductase
3. Complex IV : cytochrome c oxidase
4. Complex II : Succinate-Q reductase (some substrate use it
instead of complex I)
Other component
• Flavoproteins (I & II)
• Iron-Sulfur proteins /Fe-S (I, II & III)

19. Reaction in Respiratory Chain
Salient feature
• Substrate: Reduced coenzyme
• Product: ATP, H₂O
• Site: All cells with mitochondria
• Compartment: Inner mitochondria
• Nature: Catabolic

20. Conversion
of food
energy to
ATP

21. Electron Flow Trough Respiratory Chain

22. Inhibitors of RC Site of inhibition
Barbiturates Complex I by blocking the transfer from Fe-S to
Q
Antimycin A
Dimercaprol
Complex III
H₂S
Carbon monoxide
Cyanide
Complex IV & totally arrest respiration
Malonate Competitive inhibitor of complex II
Oligomycin Flow of protons through ATP synthase
Uncouplers:-
2,4-dinitrophenol
Thermogenin
Dissociates oxidation in respiratory chain from
phosphorylation

23. Phosphorylation
• Addition of phosphate group to an acceptor molecule by high/
low energy phosphate bond to capture the energy produced
during catabolism.
• 2 types
Oxidative
phosphorylation [at RC]
At substrate level

24. Oxidative phosphorylation
• Flow of electron through respiratory chain generates ATP by a
process called oxidative phosphorylation.
• Oxidation of reduced coenzyme & phosphorylation of ADP are
coupled
• H+ transport results in an electrochemical gradient
• Proton motive force: energy released by flow of H+ down its
gradient is used for ATP synthesis
• ATP synthase: H+ channel that couples energy from H+ flow
with ATP synthesis

25. • Use of ATP
• Synthetic reaction
• Muscle contraction
• Nerve conduction
• Active transport

26. Phosphorylation at substrate level
• ATP can also be formed in some situation when free
energy is released by a chemical reaction. This is
phosphorylation at substrate level.
• 1,3-DPG 3-DPG
ADP ATP

27. Compartments of different metabolic pathway
Cytosol Mitochondria Endoplasmic reticulum
Glycolysis TCA cycle Protein synthesis
HMP shunt RC Oxidative
phosphorylation
Cholesterol synthesis
Glycogenesis β-oxidation
Glycogenolysis Ketogenesis
Lipogenesis Deamination
Transamination
Gluconeogenesis
Urea cycle
Heme synthesis