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THIAMINE (B1)
1. THIAMINE (B1]
Gandham. Rajeev
Department of Biochemistry,
Akash Institute of Medical Sciences
& Research Centre,
Devanahalli, Bangalore,
Karnataka, India.
E-Mail: gandhamrajeev33@gmail.com
2.
3. THIAMINE B1
Thiamine (anti-beri-beri or antineuritic vitamin) is
water soluble vitamin
o It has a specific coenzyme, thiamine
pyrophosphate (TPP)
o Chemistry:
o Thiamine contains pyrimidine ring and a thiazole
ring held by a methylene bridge
4. The alcohol group of thiamine is esterfied with
phosphate (2 moles) to form the coenzyme,
thiamine pyrophosphate
(TPP or Cocarboxylase)
The phosphate moiety is donated by ATP &
reaction is catalyzed by thiamine pyrophosphate
transferase
Thiamine is a sulphur containing water soluble
vitamin
5. N
N
NH2
H3C
CH2
S
N
-CH2 - CH2 – O - P- O – P - O
O O
O O
Pyrimidine ring
Methylene bridge
Thiazole Pyrophosphate
CH3
Structure of TPP
6. Metabolism:
Absorption: Thiamin is carried by the portal blood
to the liver, present as free thiamine
Storage: stored as thiamin pyrophosphate
Mainly stored in skeletal muscle and also
present in significant amounts in liver, heart,
kidneys, erythrocytes and nervous system
Coenzyme form: TPP
7. The coenzyme, TPP or Cocarboxylase is
connected with energy releasing reactions in the
carbohydrate metabolism
Pyruvate dehydrogenase complex:
It catalyses the irreversible conversion of pyruvate
to acetyl CoA
It is essential for complete oxidation of glucose
It links glycolysis and TCA cycle
8. Transketolase is dependent on TPP
It is involved in HMP shunt
Pyruvate
Acetyl CoA
PDH Complex
NAD+
NADH + H+ TPP
9. α- Ketoglutarate dehydrogenase
complex:
It converts α- Ketoglutarate succinyl CoA in
TCA cycle
α-Ketoglutarate
Succinyl CoA
α- Ketoglutarate DH ComplexNAD+
NADH + H+
TPP
10. The branched chain α-Keto acid
dehydrogenase (decarboxylase):
It catalyses the conversion of α-keto acids to
corresponding acyl CoA
Essential for transmission of nerve impulse
TPP is required for synthesis of Acetylcholine
Branched chain α-Keto acid
Corresponding Acyl CoA
NAD+
NADH + H+ TPP
Branched chain α-Keto acid DH Complex
12. Rich sources of thiamine are unrefined cereal
grains (rice, wheat), legumes (beans)
Animal sources are liver, kidney, milk
Thiamine is mostly concentrated in outer layer of
cereals
Polishing of rice removes 80% of thiamine
Thiamine is water soluble, and is excreted into
water during cooking process
13. Adults - 1-1.5 mg/day
Children - 0.7-1.2 mg/day
Pregnancy & lactation - 2 mg/day
Deficiency :
Causes:
B1 deficiency is caused by inadequate
intake of thiamine in diet
14. Eating fishes containing microbial thiaminase, it
hydrolytically destroys thiamin
Impaired absorption is caused by intestinal
diaorders
Increased requirement of thiamine is seen in
hyperthyroidism, fever, pregnancy and lactation
Chronic alcoholism is common cause of B1
deficiency
15. BIOCHEMICAL CHANGES IN B1 DEFICIENCY
Carbohydrate metabolism is impaired
Accumulation of pyruvate in tissues
Excretion of pyruvate in urine
Normally, pyruvate does not cross the blood-brain
barrier (BBB)
In thiamine deficiency alteration occurs in BBB and
permits pyruvate into brain
It results in disturbed metabolism, it may be
responsible for polyneuritis
16. B1 deficiency leads to impairment in nerve impulse
transmission due to lack of TPP
Transketolase activity in erythrocytes is decreased
Measurement of RBC transketolase activity is
reliable diagnostic test to assess B1 deficiency
17. Thiamine deficiency causes a clinical condition
called Beri-Beri
Commonly seen in populations consuming
exclusively polished rice as staple food
Clinical features of thiamine deficiency are
grouped into
Wet beri-beri:
It is characterized by edema of legs, face, trunk &
serous cavities
18. Systolic BP is elevated & diastolic BP is decreased
Tachycardia
Fast & bouncing pulse is observed
Enlargement of heart
Heart becomes weak & death may occur due to
heart failure
19.
20. Dry beri-beri:
Associated with neurological manifestations
Clinical features
Peripheral neuritis with numbness
Tingling sensations in the lower legs & feet
Ataxic gait
Loss of weight
Muscles become weak & walking becomes difficult
Mental confusion
21. Called as Wernicke-Korsakoff syndrome
Mostly seen in chronic alcoholics
Insufficient intake or impaired absorption of
thiamine
Loss of memory,
Apathy
Rhythmical to & fro motion of eye balls
22. Seen in infants born to mothers suffering from
thiamine deficiency
The breast milk of these mothers contain low
levels of thiamine
It usually occurs during 2-4 months
Clinical features include
Sleeplessness
Restlessness
Vomiting, convulsions
Death may occur due to cardiac failure
23. Increased plasma levels of pyruvate & lactate due
to low activity of PDH complex
Accumilation of pentose sugars in erythrocytes is
due to decreased activity of transketolase
Measurement of Transketolase activity is common
test used for the diagnosis of B1 deficiency
24. Antimetabolites
Thiaminase
It is present in raw fish & seafood
Thiaminase destroys thiamine if it is present
in the diet
25. REFERENCES
Harper’s Biochemistry 25th Edition.
Fundamentals of Clinical Chemistry by Tietz.
Text Book of Medical Biochemistry-A R Aroor.
Text Book of Biochemistry-DM Vasudevan
Text Book of Biochemistry-MN Chatterjea
Text Book of Biochemistry-Dr.U.Satyanarana