Introduction of Metabolism

1. Metabolism: the beginning of a biochemical
saga
Dr. Mohammad Shiblee Zaman
Lecturer (Biochemistry)
Dhaka Medical College

2. Lumen of GIT Intestinal cell Blood Cell
.. .
. ..
.. .
.
Digestion
Absorption Metabolism

3.  Digestion →
break down to simple absorbable unit
 Absorption →
transport from lumen to intestine to blood

4. Metabolism
A sequence of chemical reactions that begins with a
particular molecule & results in formation of some other
molecule(s) in a carefully defined fashion.

5. Metabolism
Catabolism………………….generates ATP
Fuel (carbohydrates, fats) → CO2 + H2O + ATP
Anabolism…………………..utilizes ATP
ATP + simple precursors → complex molecules
Catabolism
Anabolism

6. Catabolism vs. anabolism

7. Metabolic pathway
Catabolic e.g. glycolysis
Anabolic e.g. protein synthesis
Amphibolic e.g. TCA cycle

8. Phases of catabolism
Carbohydrate
Protein
Fat
Glucose
Amino acid
Fatty acid
& glycerol
Acetyl coA
Acetyl coA
oxidation
1st phase 2nd phase 3rd phase
TCA
cycle

9. Respiratory chain
TCA cycle
Metabolic paradigm
Carbohydrate
Protein
Fat
Glucose
Amino acid
Fatty acid
& glycerol
Catabolism/
Oxidation
NAD2H
/ FADH2
Primary
metabolism
Secondary/
intermediary
metabolism
Tertiary
metabolism
Anabolism
AT
P
H20

10. Some basic metabolite: structure
Glucose:
CH2OH–CHOH–CHOH–CHOH–CHOH–CHO
Fatty acid:
CH3–(CH2)n–CH–COOH

11. Some basic metabolite: structure
NH2
Amino acid: │
CH3–(CH2)n–CH–COOH
Glycerol:
CH2–OH
│
OH–CH
│
CH2–OH

12. Metabolic fuel
Glucose…………………universal
Fatty acid
Amino acid……………...least preferred
Ketone bodies………….fasting & starvation
e.g. acetoacetate, β-hydroxy butyric acid
“not acetone”

13. Fuel for brain/ neuron
Glucose…………….রসগ োল্লো
Ketone bodies

14. Fuel for heart/ cardiac muscle
Fatty acid……………………….রসগ োল্লো
Ketone bodies
Glucose…..least preferred……করল্লো

15. Fuel for skeletal muscle
Glucose
Fatty acid
Ketone bodies

16. Fuel for RBC
Glucose

17. Fuel for liver/ hepatocytes
Fatty acid
Glucose
Lactic acid

18. ATP – ADP cycle
Generation & utilization of ATP (energy).
40% free
energy……….ATP
60% free
energy……….heat
ATP-ADP cycle
Energy utilization
•Biosynthesis
•Detoxification
•Muscle contraction
•Active ion transport
•Thermogenesis
Energy production
•Catabolism
Heat

19. ATP homeostasis
Maintenance of cellular ATP content.
Negative feedback control.
ATP content high………..anabolic mode (↓ catabolism).
ATP content low……….. catabolic mode (↓ anabolism).

20. Oxidation
Addition of oxygen to a compound.
Removal of hydrogen from a compound.
Removal of electron from an ion or atom i.e. ↑ in
positive charges.
Oxidation is always accompanied by reduction.
2Cu + O2 → 2CuO
Fe++ → Fe+++ + e-
CH2-COOH CH-COOH
I → II
CH2-COOH HOOC-CH
Succinate Fumarate

21. Reduction
Removal of oxygen from a compound.
Addition of hydrogen to a compound.
Addition of electron to an ion or atom i.e. ↓ in positive
charges.
0 OH
II I
CH3-C-COOH + 2H → CH3-CH-COOH
Pyruvate Lactate

22. Biological oxidation
 Oxidation of biomolecules/ metabolic fuels in biological
system by enzymes and coenzymes.
 Catalyzed by oxidoreductases.
 Purpose: Energy & heat.

23. Oxidoreductases
Dehydrogenases
Oxidases
Oxygenases
Peroxidases
Catalases

24. Dehydrogenation
Oxidized co-
enzyme (NAD/
FAD)
Biomolecules (M2H)
Reduced co-enzyme
(NAD2H/ FADH2)
M (oxidized form)
Dehydrogenase
Commonest mechanism of biological oxidation.
Catalyzed by dehydrogenases.

25. Oxidized co-enzyme: NAD, FAD
Limited pool.
Need Niacin & Riboflavin.
Niacin & Riboflavin…….essential nutrient.

26. Reduced co-enzyme: recycling
Recycling done by:
Reductive synthesis of fatty acid, steroid, cholesterol etc.
Respiratory chain/ electron transport chain (ETC)
(oxidative phosphorylation)
Oxidized co-enzyme
(NAD, FAD)
Reduced co-enzyme
(NAD2H, FADH2)

27. Reductive synthesis
NAD2H
FADH2
NAD
FAD
NAD
P
NADP2
H
NAD
P
Acetyl coA
FA/
cholesterol/
steroid

28. Respiratory chain: components
Complex I
FMN
Complex II
FAD
Complex III
Cyt.b→Cyt.c
1
Complex IV
Cyt.aa3
Cyt.
c
CoQ
NAD
Cyt.aa3………………cytochrome oxidase

29. Operational view of respiratory chain
NA
D
FM
N
Co
Q
Cyt.
b
Cyt.c1
M2H
M
Cyt.
c
Cyt.aa
3
FAD2
H
M2H
M
AT
P
AT
P
AT
P
2H+
½ O2
H20
2H 2e-
2H 2H 2e- 2e- 2e-

31. Intermembrane space
Matrix
ETC
Chemiosmosi
s
Oxidative Phosphorylation
IMM
V
I
Co
Q
III
II
IV
Cyt.c

32. II
Cyt.c
Intermembrane space
Matrix
IMM
IV
III
I
Co
Q V
NAD2H
NAD+
H
+
e-
H
+
H
+
H
+
H
+
H
+
H
+
FADH2
FAD
e-
e-
e-
H
+
H
+
H
+
H
+
e-
e-
H
+ H
+
½ O2
H20
2H+
H
+
H
+
H
+
H
+
H
+
H
+
H
+
ADP +
Pi
ATP
H
+

33. Respiratory chain (ETC): salient feature
Substrate : Reduced coenzyme (NAD2H, FADH2)
Product : ATP & H2O
Site : All mitochondria containing cell
Compartment : Inner mitochondrial membrane
Nature : Catabolic
Key enzyme : Cytochrome oxidase & ATP synthase

34. O2
2H
H2O
ETC
AT
P
NAD/ FAD
NAD2H/
FADH2
1
NAD2H…………3ATP
1
FADH2…………2ATP

35. Major Sources of ATP
1. Respiratory chain (ETC)
2. Glycolytic pathway
3. TCA cycle

36. Inhibitors of ETC
1. Barbiturates
2. Dimercaprol
3. Inhibitor of cytochrome oxidase
Cyanide
Carbon monoxide
Hydrogen sulfide

37. ETC dysfunction
Hypoxic cell injury
Mitochondrial myopathy
Mitochondrial neuropathy
Mitochondrial encephalopathy
Stroke etc.

38. Hypoxic cell injury
ETC dysfunction.
Less ATP production.
Suppressions of Na+-K+ pump.
Na
+
K+ Use 45% of BMR

39. Sodium entry into cells.
Increased ICF osmotic pressure.
Water entry into cells.
Increased ICF hydrostatic pressure.
Cell swelling & cell injury.

40. Thank you.