The document discusses several important co-enzymes: NAD+, FAD, lipoic acid, and thiamine pyrophosphate. It describes their structures and roles in biochemical reactions. NAD+ acts as an electron carrier in redox reactions, accepting or donating electrons. FAD is first reduced to FADH2 by NADH and can then transfer electrons to oxygen via cytochromes. It participates in oxidation reactions via either a hydride transfer or adduct formation mechanism. Lipoic acid functions as an electron transfer cofactor in ATP production and the conversion of pyruvate to acetyl-CoA. Thiamine pyrophosphate contains an active thiazolium ring

1. BIOMOLECULES III
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2. Chemistry of co - enzymes
• Biochemical reactions are enzyme controlled, but often
enzymes needs second substrate (Co-enzymes) in order to
express its catalytic activity.
• They are either non- protein organic substance or a metal ion
or both.
• Also known as co- factors or vitamins.
• Without these co- enzymes many biological reactions cannot
occur.
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3. Some Important co-enzymes
• NAD+ ( Nicotinamide adenine dinucleotide)
• FAD (Flavin adenine dinucleotide)
• TPP (Thiamine pyrophosphate)
• Pyridoxal phosphate
• Vitamin B12
• Biotin
• Lipoic acid
• Coenzyme A
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4. NAD+ ( Nicotinamide adenine dinucleotide)
Structure:
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5. NAD+ ( Nicotinamide adenine dinucleotide)
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6. NAD+ ( Nicotinamide adenine dinucleotide)
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7. NAD+ ( Nicotinamide adenine dinucleotide)
• NAD+ / NADH co-enzyme is involved in hydrogenase /
dehydrogenase enzyme system.
• Dihydropyridine ring or pyridinium ring of NAD+ is the reactive
portion.
• NADH is involved in the reaction by the transfer of hydride ion
& the product is oxidized.
• Eg.
1.
2.
CH3 C COOH
O
NADH
CH3 CH COOH
OH
+ NAD
+
pyruvic acid Lactic acid
CH3 CHO
NADH
CH3 CH2 OH + NAD
+
ethanolacetaldehyde
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8. NAD+ ( Nicotinamide adenine dinucleotide)
• In metabolism, the compound accepts or donates electrons in
redox reactions.
• Reactions involve the removal of two hydrogen atoms from the
reactant (R), in the form of a hydride ion (H−), and a proton (H+).
The proton is released into solution, while the reductant RH2 is
oxidized and NAD+ reduced to NADH by transfer of the hydride to
the nicotinamide ring.
• RH2 + NAD+ → NADH + H+ + R;
• From the hydride electron pair, one electron is transferred to the
positively charged nitrogen of the nicotinamide ring of NAD+, and
the second hydrogen atom transferred to the C4 carbon atom
opposite this nitrogen. The midpoint potential of the NAD+/NADH
redox pair is −0.32 volts, which makes NADH a strong reducing
agent. The reaction is easily reversible, when NADH reduces
another molecule and is re-oxidized to NAD+. This means the
coenzyme can continuously cycle between the NAD+ and NADH
forms without being consumed.
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9. NAD+ ( Nicotinamide adenine dinucleotide)
• Mechanism of action:
Reduction reaction:-
1.
2.
N
DH
R
NH2
O
where X = Cl, -OH, -NH2, -OR
CH3
X
O
O CH3
X
OH
O
D + NAD
+
N
HH
R
NH2
O
CH3
X
O
O CH3
X
OD
O
H + NAD
+
D2O
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10. NAD+ ( Nicotinamide adenine dinucleotide)
• Hydrogen present at C4 position of the pyridine ring is
transferred to the acceptor in the form of ‘H’ directly.
• Evidence:- when deuterium is present at C4 position , ‘D’
occurs in the product.
• No deuterium is exchanged when solvent is deuterated.
N
DH
R
NH2
O
N
N
H
DH
+ NAD
+
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11. NAD+ ( Nicotinamide adenine dinucleotide)
Bio- modeling studies:-
• 2 common models are:
1. 1- Benzyl or N- Benzyle-1,4- Dihydro nicotinamide
2. Hanztsch ester
N
HH
CH2Ph
NH2
O
N
HH
CO2EtEtO 2C
CH3
CH3CH3
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12. NAD+ ( Nicotinamide adenine dinucleotide)
N
HH
CH2Ph
NH2
O
CH3
OH
O
O CH3
OH
OH
O
H + NAD
+
CN
CNPh
H
Ph
CN
NC8/9/2020 12Savita K.

13. NAD+ ( Nicotinamide adenine dinucleotide)
N
HH
CO2EtEtO 2C
CH3
CH3CH3
Ph
N Ph
Ph S S Ph
Ph
NH Ph
2PhSH
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14. NAD+ ( Nicotinamide adenine dinucleotide)
• Mg+2 & Zn+2 are used in reduction to co-ordinate with α- keto
carbonyl compounds.
• Example: Reduction of 1,10-phenanthroline-2-carbaldehyde is
carried out by N-propyl-1,4-dihydronicotinamide only when
the molecule is activated by Zn+2 ions.
• This indicates that Zn+2 ions are involved in coordination to
enhance the electrophilicity of aldehyde functional group.
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15. N
N
O H
N
HH
CH2CH2CH3
NH2
O
N
N
O H
Zn
+2
N
N
CH2OH
+
N
+
(CH2)2CH3
NH2
O
NAD+ ( Nicotinamide adenine dinucleotide)
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16. FAD (Flavin adenine dinucleotide)
Structure:
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17. FAD (Flavin adenine dinucleotide)
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18. FAD (Flavin adenine dinucleotide)
• FAD is first reduced to FADH2 by NADH which is a better
reducing agent than NADH.
• FADH2 (reduced form) can transfer one or both electrons to
oxygen via cytochrome co-enzymes.
• One O- atom is incorporated into the substrate & other
appears as water.
FAD + NADH FADH2 + NAD
+
FADH 2
O2* + RH
cytochrome P450
H2O* + ROH* + FAD
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19. FAD (Flavin adenine dinucleotide)
Some typical oxidation reactions shown by FAD:-
1.
2.
O
H
H
H
H
OH
OH
H OH
OH
OH
+ FAD
O
H
H
H
OH
OH
H OH
O
OH
beta - D - glucose glucanolactone
+ FADH 2
COO
-
H
R
NH3
+
FAD
FADH2
COO
-
R
NH2
+
H2O
COO
-
R
O
+ NH3
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20. FAD (Flavin adenine dinucleotide)
Mechanism of action:
a) Hamilton Mechanism
b) Bruice mechanism
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21. FAD (Flavin adenine dinucleotide)
Bruice (Hydride transfer) Mechanism:-
• Reduction of FAD to FADH2 by NADH was unsolved for long
time.
• FAD structure has atleast 3 prominent electrophilic sites ( N-5,
C-4, C-10) to which attack can take place by hydride
equivalent.
N
N
NH
N
R
O
O
CH3
CH3
N
N
H
NH
N
H
R
O
OCH3
CH3
NADH
FAD FADH2
+ NAD
+
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22. FAD (Flavin adenine dinucleotide)
• In this there is direct hydride transfer from the substrate to the 5th
position of FAD. Proton is accepted at position 1.
N
N
NH
N
R
O
O
CH3
CH3
N
N
H
NH
N
H
R
O
OCH3
CH3
FAD FADH2
+ NAD
+
+
N
HH
CONH 2
R
H- Enzyme
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23. FAD (Flavin adenine dinucleotide)
• If deuterated NADH is used then no direct conclusion was made to
prove the direct hydride transfer mechanism as it would rapidly
exchange with the medium (proton exchange).
N
N
NH
N
R
O
O
CH3
CH3
N
N
NH
N
H
R
O
OCH3
CH3
D
FAD FADH2
+
N
DD
CONH 2
R
H- Enzyme
H2O
proton exchange
-DOH
N
N
H
NH
N
H
R
O
OCH3
CH3
FADH 2
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24. FAD (Flavin adenine dinucleotide)
Bio- modeling studies:-
• Bruice & co – workers prepared 5-deaza flavin model &
treated with NaOH in D2O. It was observed that the C-5
position gets H whereas N-1 position gets Deuterium.
N
NH
N
CH3
O
O
CH3
CH3
N
NH
N
R
O
OCH3
CH3
HH
D
5 - deaza flavin model
+ NAD
+NADH
D2O
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25. FAD (Flavin adenine dinucleotide)
• In support of Bruice mechanism , Walsh gave the following
reaction:
N
NH
N
CH3
O
O
CH3
CH3
N
NH
N
R
O
OCH3
CH3
HH
D
+ NAD
+
NADT
H2O
+
N
TH
R
CONH 2
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26. FAD (Flavin adenine dinucleotide)
Hamilton Mechanism:
• Hamilton proposed that FAD reduction by NADH does not
involve either hydride or electron transfer but occurs via a
covalent adduct formation at C4a position.
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27. N
N
NH
N
R
O
O
CH3
CH3
+
N
HH
R
NH2
O
N
N
NH
NCH3
CH3
R
H
O
O
O
NH2
N
+
HH
R
- H+
, H+ N
N
H
NH
N
H
R
O
O
CH3
CH3
FAD NADH
FADH2
+
N
+
NH2
O
R
NAD
+
C4a adduct
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28. FAD (Flavin adenine dinucleotide)
Bio- modeling studies:-
• Support for adduct formation is provided by N-methyl-5-(p-
nitrophenylimino) barbituric acid as the model compound.
• Hamilton also proposed that oxidation of alcohol to carbonyl
compound occurs via adduct formation.
O2N
N
NH
NO
O
O
CH3
+
SH
O2N
NH
NH
NO
O
O
CH3
S
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29. N
N
NH
N
R
O
O
CH3
CH3
+
- H+
, H+ N
N
H
NH
N
H
R
O
O
CH3
CH3
FAD
FADH2
+
C4a adduct
R
OH
R
H
Sec. alcohol
N
N
NH
NCH3
CH3
R
H
O
O
O
H
R R
R
O
R
Ketone
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30. FAD (Flavin adenine dinucleotide)
Mechanism of Oxygen Activation:
FADH 2
O2* + RH
cytochrome P450
H2O* + ROH* + FAD
N
N
H
NH
N
H
R
O
O
CH3
CH3
N
N
H
NH
N
R
O
O
CH3
CH3
O
OH
FAD
N
N
NH
N
H
CH3
CH3
R
H
O
O
O
O
O2*
*
*
Peroxidase
*
*
- H2O*
N
N
NH
N
R
O
O
CH3
CH3
O
FAD Oxeridine
RH
RO*H + FAD
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31. Lipoic Acid
• Chemical name: 1,2-dithiolane-8-valeric acid
• Structure:
• It is a Sulphur containing co- factor; coupled with Thiamine co-
enzyme.
• Functions as an electron transfer co- factor where net
oxidation, reduction produces ATP.
• Conversion of pyruvate to Acetyl CoA is done by multienzyme
complex pyruvate dehydrogenase ( system of 3 enzymes)
which requires 5 co- enzymes, lipoic acid is one of them.
SS
COOH
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32. Lipoic Acid
Structure Activity relationship:
• 5 – membered ring has strain which is further increased by
repulsion of electron pairs on adjacent sulphur atoms.
• Thus 5 – membered rings can be easily reduced compared to
6 – membered ring. Therefore a better oxidising agent.
• Readily reduced by NaBH4 or with mineral acid & the reduced
form (Dihydrolipoic acid) can be oxidized by iodine in water.
S
SHOOC
SS
COOH
Lipoic acid (LA)
NaBH4 or H+
I2/ O2
COOH
SH SH
Dihydrolipoic acid (DHLA)
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33. Lipoic Acid
• Dihydrolipoic acid is an efficient reducing agent for conversion
of sulphate ion to sulphite ion.
Mechanism is as follows:
1. Sulphate ion is activated as an active anhydride by ATP
S O
-
O
O
-
O
+ P O
O
O
-
O
-
ADP S O
O
O
-
O O
-
O
P O
-
+ ADP
ATP Mixed anhydride
SH SH
R
DHLA, PO4
-
S O
O
O
-
S
+
SHH
R
+ PO 4
-
S O
O
O
-
S SH
R
-H+
SS
R
LA
+ S O
-
O
O
-
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34. Lipoic Acid
• Reductive acylation of lipoic acid during pyruvic acid
decarboxylation:
Mechanism:
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35. Thiamine Pyrophosphate (TPP)
Structure
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36. Thiamine Pyrophosphate (TPP)
• Thiazolium ring is the active moiety which brings about
umpolung like cyanide ion.
• Also known as Biological cyanide equivalent.
• Due to presence of positive charge on ‘N’, there is electron
withdrawal from the C-2 position as a result the C-2 hydrogen
is sufficiently acidic & can be abstracted even by weak bases
to give thiazolium ylide.
• In biological system the amino group of pyrimidine ring can
abstract proton (C-2) to give thiazolium ylide.
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37. Thiamine Pyrophosphate (TPP)
• Proof of thiazolium ylide formation – R. Breslow (1947- by
NMR studies).
• A model of thiazolium salt in D2O in presence of triethylamine
was found to exchange C2 – hydrogen by Deuterium.
• This exchange of H by D occurs via thiazolium ylide.
N
+
S
H
CH3
D2O
Et3N
C
-
N
+
S
CH3
N
+
S
D
CH3
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38. Thiamine Pyrophosphate (TPP)
Metabolic functions:
• Required by enzymes that transfer a 2 carbon fragment from
one species to another.
• Example: Pyruvate decarboxylase, Pyruvate dehydrogenase,
Acetolactate synthase, Transketolase.
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39. Thiamine Pyrophosphate (TPP)
Mechanism of decarboxylation of pyruvic acid:
pyruvate + thiamine pyrophosphate (TPP) → hydroxyethyl-TPP + CO2
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40. Thiamine Pyrophosphate (TPP)
Mechanism of Acyloin condensation:
CH3OH
OO
+ C
-
N
+
S
CH3
R
R
CH3
OH
O
-
O N
+
S
CH3
R
R
H - exchange
CH3
O
-
OHO N
+
S
CH3
R
R
- CO2
N
S
CH3
R
R
OH
CH3
CH3 H
O
CH3
CH3
OHO
-
N
+
S
CH3
R
R
H
proton transfer CH3
OH
CH3
O
-
N
+
S
CH3
R
R
CH3CH3
OOH
Acyloin
+
C
-
N
+
S
CH3
R
R
pyruvic acid
acetaldehyde
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41. Thiamine Pyrophosphate (TPP)
Bio- modeling studies:-
• Few bio- model of thiamine have been studied & many reactions
performed by TPP can be duplicated in the laboratory.
• Benzyl bromide is treated with thiazolidine for the formation of thiazolium
salt.
PhCH 2Br +
N
S
Benzyl bromide Thiazolidine
N
+
S
CH2Ph
Thiazoliumsalt
pH 8 - 9
CH3COCOOH
CH3CHO + CO2
pH 8 - 9 PhCHO
N
S
CH2Ph
H5C6
OH
C6H5CHO
H5C6 C6H5
OH O
Benzoin
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42. Thiamine Pyrophosphate (TPP)
N
+
S
CH2Ph
H CH3
X
- N
+
S
CH3
CH3
X
-
Thiazoliummodels
Effective Not effective
No acidic proton
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43. Pyridoxal Phosphate (PLP)
Structure:
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44. Pyridoxal Phosphate (PLP)
• It is a prosthetic group of certain enzymes.
• PLP is also the active form of vitamin B6, which comprises of
three natural organic compounds pyridoxal, pyridoxine &
pyridoxamine.
• This co-factor acts as an electron sink to stabilize carbanionic
intermediates in both substitution and elimination reactions
involving aminated compounds
• Natures most potent co – enzyme involving transamination,
elimination, hydrolysis, decarboxylation etc.
• Exists mainly as pyridoxal phosphate in living organisms.
• Catalyzes several mechanisms involving simple acid – base
chemistry.
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45. Pyridoxal Phosphate (PLP)
Pyridoxine Pyridoxal
Pyridoxamine
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46. Pyridoxal Phosphate (PLP)
1. Trans amination:
2. Elimination hydrolysis:
R COOH
O
+ R
1
COO
-H
NH3
+
R COO
-H
NH3
+
R
1
COOH
O
+
Keto acid amino acid
PLP
COO
-
NH3
+
OH
Serine
pyridoxal
- H2O
CH2 COO
-
NH3
+
CH3 COO
-
NH2
+
CH3 COOH
O
+ NH3
Pyruvic acid
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47. Pyridoxal Phosphate (PLP)
3. Elimination hydration:
4. Decarboxylation:
O
-
P O CH2 CH2 CH COO
-
NH3
+
O
O
-
PLP
CH2 CH CH COO
-
NH3
+
Homo serine phosphate
H2O
CH3 CH CH COO
-
NH3
+
OH
Threonine
CH2 CH2 CH COO
-
NH3
+
HOOC
pyridoxal
- CO2
Glutamic acid
CH2 CH2 CH2HOOC NH2
GABA
Γ- amino butyric acid
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48. Pyridoxal Phosphate (PLP)
5. Reverse condensation:
6. Epimerization:
7. Tryptophan synthesis:
OH CH2 CH COO
-
NH3
+
HCHO + NH3
+
CH2 COO
-
formaldehyde glycine
NH3
+
H
R
COO
-
NH3
+
O
-
OC
R
H
COO
-
NH3
+
R
H
+
pyridoxal
N
H
+ OH CH2 CH COO
-
NH3
+
pyridoxal
N
H
CH2 CH COO
-
NH3
+
Indole Serine Tryptophan
Serine
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49. Pyridoxal Phosphate (PLP)
Mechanism of trans amination:
N
OH
CH3
CHO
RO
pyridoxal co - enzyme
NH2 -- Enzyme
N
OH
CH3
RO
N --Enzyme
pyridoxal enzyme complex
(Schiff's base)
R
1
COO
-
NH3
+
NH2 -- Enzyme
N
OH
CH3
RO
N
COO
-
R
1
H
pyridoxal amino acid complex
H+
activation
N
H
+
OH
CH3
RO
N
COO
-
R
1
H
- H+
N
H
OH
CH3
RO
N
COO
-
R
1
H+
N
H
+
OH
CH3
RO
N
COO
-
R
1
N
OH
CH3
CH2NH2
RO
pyridoxamine
+ COO
-
O
R
1
keto acid8/9/2020 49Savita K.

50. Pyridoxal Phosphate (PLP)
Reverse of above reaction:
N
OH
CH3
CHO
RO
pyridoxal co - enzyme
R
1
COO
-
NH3
+
+
N
OH
CH3
CHO
RO
pyridoxal co - enzyme
+ R
1
COO
-
NH3
+
+ COO
-
O
R
1
keto acid
N
OH
CH3
CH2NH2
RO
pyridoxamine
N
OH
CH3
CH2NH2
RO
pyridoxamine
+ COO
-
O
R
1
keto acid
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51. Pyridoxal Phosphate (PLP)
Mechanism of decarboxylation:
N
OH
CH3
CHO
RO
pyridoxal co - enzyme
NH2 -- Enzyme
N
OH
CH3
RO
N --Enzyme
pyridoxal enzyme complex
(Schiff's base)
R
1
COO
-
NH3
+
NH2 -- Enzyme
N
OH
CH3
RO
N
COO
-
R
1
H
pyridoxal amino acid complex
H+
activation
N
H
+
OH
CH3
RO
N
R
1
H
O
-
O
N
H
OH
CH3
RO
N
H
R
1
H+
N
H
+
OH
CH3
RO
N
H
R
1
N
OH
CH3
CHO
RO
pyridoxal
+
primary amine
- CO2
H2O
R
1
NH2
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52. Pyridoxal Phosphate (PLP)
Bio- modeling studies:-
• Most of the reactions catalyzed by PLP co- enzyme have been
reproduced in the laboratory.
• Essential characteristics to be an effective model:
i) Presence of –CHO
ii) Adjacent –OH group w.r.t.–CHO
iii) Para position w.r.t. –CHO must be electron sink
(withdrawing)
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53. Pyridoxal Phosphate (PLP)
• Following model compounds have been found to be effective:
• Following model compounds have been found to be non -
effective:
N
CHO
OH
CH3 N
CHO
OHCH3
pyridine models
CH3
OH
NO2 Non - pyridine model
N
OH
CHO
CH3 N
OH
CHOCH3
CH3
OH
CHOCH3
NO2
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54. Pyridoxal Phosphate (PLP)
Role of –OH group:
• Stabilizes amino acid pyridoxal Schiff’s base & also activates it for trans
amination, decarboxylation.
• Al+3 salt is added to increase the rate of reaction. Al+3 complex facilitates
deprotonation / decarboxylation thus the presence of adjacent –OH group
is essential for chelate formation ie; activation.
N CH3
RO
N
O
-
OC
R
1
H
O
H H - Bonding
N
N
O
Al
+3
N
OH
N
Al+3
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55. Biotin
Structure:
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56. Biotin
• Biotin, also known as vitamin H or coenzyme R.
• It is composed of a tetrahydroimidizalone)ring fused with
a tetrahydrothiophene ring. A valeric acid substituent is attached to
one of the carbon atoms of the tetrahydrothiophene ring.
• Biotin is a coenzyme for carboxylase enzymes, involved in the
synthesis of fatty acids, isoleucine, and valine, and
in gluconeogenesis.
• Serves as carboxyl group carrier in a series of β- carboxyl reaction.
• Examples are carboxylation of co- enzyme pyruvate carboxylation,
propyonyl carboxylation, malonyl carboxylation.
O
-
enolate
+ CO2
biotin, ATP
enzyme
O
O
O
-
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57. Biotin
Mechanism of carboxyl activation by biotin:
• Bicarbonate is incorporated in the biotin in presence of ATP (1968
– Lynein)
• When carbonate ion having all the 3 O – atoms labeled as O18 was
used, it was observed that 2 O18 atoms appeared in E-biotin
carboxylate complex & one is observed in the phosphate group.
Biotin + Enzyme
Enzyme Biotin
Enzyme Biotin
+ +HCO 3
-
ATP E--Biotin --CO 2
-
+ ADP + PO 4
3-
Acceptor RH
RCOO
-
+ Enzyme Biotin
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58. Biotin
• Although many mechanistic proposals have put forward, basically
two of them are more interesting:
(a) In the first mechanism it is proposed that carbonate ion reacts
with ATP to form active anhydride intermediate, which then
reacts with biotin ( less hindered amide nitrogen) to give N –
carboxyl complex & phosphate ion.
O
-
O
-
O
O
PADP
ATP
+
OH
O
O
-* *
O
O
-
O
O
-
P OH
O
* *
NH NH
S
O
R
Biotin
N NH
S
O
R
O
H
O
*
+ PO4
3-
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59. Biotin
(b) In the second proposal the molecule of ATP reacts at the
oxygen of amide of biotin to give enol phosphate.
O
-
O
-
O
O
PADP
ATP
+
PO 4
3-
OH
O
O
-
NH NH
S
O
R
Biotin
NH NH
S
R
O O
-
O
-
O
P
+ ADP
NH
+
NH
S
R
O
O
-
O
-
O
P
-
O OH
O
+
NH N
S
O
R
OH
O
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60. Biotin
Evidence:
• Trapping of intermediate with a diazomethane yields a stable ester
derivative.
• Thomas & co- workers proposed that carboxylation occurs first at
the O- atom of biotin rather than N – atom; amide N gives O-
carboxyl biotin.
NH N
S
O
R
OH
O*
* CH2N2 NH N
S
O
R
OCH 3
O
+ N2
NH NH
S
O
R
+
N NH
S
O
O
OH
R
CH2N2 NH
+
NH
S
O
O
OCH 3
R
NH N
S
O
OCH 3
O
R
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61. Biotin is the coenzyme for 4
carboxylases.
 1. Acetyl coenzyme A carboxylase : found in the
mitochondria; catalyzes the carboxylation of Acetyl
Co A to Malonyl Co A.
 2. Pyruvate carboxylase : found in the mitochondria;
catalyzes the carboxylation of pyruvate to form
oxaloacetate.
 3. Methylcrotonyl –Co A carboxylase : found in the
mitochondria; involved in the metabolism of L- leucine.
 4. Propionyl -Co A carboxylase : involved in the
metabolism of L-isoleucine, L-valine, L-threonine, and
L-methionine.8/9/2020 61Savita K.

62. Acetyl coenzyme A carboxylase
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63. Propionyl –Co A carboxylase
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64. Pyruvate carboxylase
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65. Co – enzyme A
Structure:
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66. Co – enzyme A
Adenine
Glycosidic linkage
Β- mercapto
ethyl
amine
Β- alanine Pantothenic acid
Abbreviated as CoASH
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67. Co – enzyme A
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68. Co – enzyme A
Function
• Since coenzyme A is, in chemical terms, a thiol, it can react
with carboxylic acids to form thioesters, thus functioning as
an acyl group carrier.
• It assists in transferring fatty acids from
the cytoplasm to mitochondria.
• A molecule of coenzyme A carrying an acetyl group is also
referred to as acetyl-CoA. When it is not attached to an acyl
group, it is usually referred to as 'CoASH' or 'HSCoA'.
• Coenzyme A is also the source of
the phosphopantetheine group that is added as a prosthetic
group to proteins such as acyl carrier
protein and formyltetrahydrofolate dehydrogenase.
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69. • Acetyl coenzyme A or acetyl-CoA is an important molecule
in metabolism, used in many biochemical reactions.
• Its main function is to convey the carbon atoms within
the acetyl group to the citric acid cycle (Krebs cycle) to
be oxidized for energy production.
• In chemical structure, acetyl-CoA is
the thioester between coenzyme A (a thiol) and acetic
acid (an acyl group carrier).
• Acetyl-CoA is produced during the second step of
aerobic cellular respiration, pyruvate decarboxylation, which
occurs in the matrix of the mitochondria.
• Acetyl-CoA then enters the citric acid cycle
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70. Co – enzyme A
Metabolic functions of Acetyl co – enzyme A:
1. Universal acetylating agent.
2. Biosynthesis of poly carboxylic acid like citric acid.
3. Biosynthesis of fatty acids.
4. Oxidation of fatty acids.
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71. Co – enzyme A
• Biosynthesis of poly carboxylic acid:
• Mechanism:
COOH
COOH
O
oxaloacetic acid
Enzyme -H
+ CH2 SCoA
OH
CH2 COOH
C
COOH
CH2OH C
O
SCoA
H2O
CH2 COOH
C
COOH
CH2OH C
O
OH
+ CoASH
:B -Enzyme
enol form
Citric acid
COOH
COOH
O + CH3 SCoA
O
CH2 COOH
C
COOH
CH2OH C
O
SCoA
H2O
CH2 COOH
C
COOH
CH2OH C
O
OH + CoASH
oxaloacetic acid
Citric acid
(Citric acid synthesis)
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72. Co – enzyme A
• Biosynthesis of fatty acids:
1. Anabolic pathway i.e.; reductive reagents are used.
2. Naturally occurring fatty acids contain even number of
carbons as every time two C-atoms of acetyl CoA are added.
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73. Co – enzyme A
• This is the first cycle of fatty acid synthesis.
• Net result is conversion of 2 acetate units into 4 butyrate unit.
• After this another cycle begins & chain is lenghthen by 2 more C – atoms.
CH3 C SCoA
O
+ CO2
ATP
CH2C SCoA
O
COH
O
Malonyl CoA(Acetyl CoA carboxylase )
CH3 C SCoA
O
+ CH2C SCoA
O
COH
O
Acetyl CoA
Acetyl CoA Malonyl CoA(Acetyl CoA carboxylase CO2
CoASH
CH2C SCoA
O
CCH3
O
Acetoacetyl CoA
NaDPH
H
+
NaDP Reduction
CH2C SCoA
O
CHCH3
OH
- H2O
CH C SCoA
O
CHCH3
Crotonyl CoA
NaDPH, H+
- NADP+
CH2C SCoA
O
CH2CH3
Butyryl CoA
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74. Co – enzyme A
CH2C SCoA
O
CH2CH3
Butyryl CoA
+ CH2C SCoA
O
COH
O
Malonyl CoA(Acetyl CoA carboxylase )
- CO2,
- CoASH
CH2C SCoA
O
CCH2
O
CH2CH3
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75. 8/9/2020 Savita K. 75