Coenzyme chemistry

1. Thiamine
pyrophosphate(TPP)
(Co-enzyme Chemistry)
Presented to:- Dr.Rajesh k.Sharma
Presented by:- Anmol
M.Sc.Chemistry 2nd year (4th sem)
Roll no:- 4853
Practical paper code:- CH525
Session:- 2020-2021
Date:- 15/6/2021
TOPIC:- Structure, biological functions and
reactions catalyzed by TPP

2. Introduction :
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Thiamine is a white crystalline compound,
readily soluble in water but insoluble in fats.
Thiamine is also known as Vitamin B1 ,anti
beriberi factor or anti neuritic vitamin.
Thiamine occurs in the human body as free
thiamine and its phosphorylated form :
# Thiamine monophosphate(TMP);
# Thiamine triphosphate(TTP);
# Thiamine pyrophosphate(TPP) which is also
known as thiamine diphosphate.

3. Structure of thiamine
pyrophosphate (TPP) :
• Thiamine pyrophosphate(TPP) contains two
ring systems:
A pyrimidine
A thiazole

4. Biological functions of TPP:
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TPP maintains the normal function of heart.
TPP maintains the carbohydrate and energy-yielding
metabolism.
TPP has a role in nerve conduction.
TPP works as a coenzyme in many enzymatic reaction
such as:
(1) Pyruvate decarboxylase
(2) Transketolase
(3) Pyruvate dehydrogenase
(4) Alpha ketoglutarate dehydrogenase

5. Reactions catalyzed by TPP :
(1) TPP as an essential cofactor of pyruvate
decarboxylase:
Decarboxylation of pyruvate form acetaldehyde
and CO2 which is catalyzed by pyruvate
decarboxylase (PDC) and coenzyme TPP.
In TCA cycle, TPP acts as a coenzyme for
pyruvate decarboxylase to decarboxylate pyruvic
acid and alpha-ketoglutaric acid

6. Mechanism of pyruvate
decarboxylase:
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Step1: Nucleophilic attack by the ylid form of TPP on the
carbonyl carbon of pyruvate to form a covalent adduct.
Step2: CO2 released and resonance stabilized Carbanion
adduct form, thiazolium ring of coenzyme acts as an
electron sink.
Step3: Protonation of the
Carbanion.
Step4: Regeneration of
active enzyme and
acetaldehyde formed.

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(2) TPP as coenzyme for Transketolase :
Xylulose-5-phosphate(Xu5P) transfer C2 unit to
Ribose-5-phosphate(R5P) , yielding Sedoheptulose-7-
phosphate(S7P) and Glyceraldehyde-3-
phosphate(GAP).
The reaction occurs as follows :
The TPP ylid attacks the carbonyl group of Xu5P.
C2-C3 bond cleaves yields GAP and enzyme bound 2-(1,2-
dihydroxyethyl)-TPP, resonance-stabilized Carbanion.
C2 carbanion attacks the aldehyde carbon of R5P forming an
S7P-TPP adduct.
TPP is eliminated yielding S7P and regenerated TPP-enzyme.

8. Mechanism of Transketolase:
• Reaction occurs as follows:

9. THANK
YOU