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

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

11. Glucose Glucose – 6 P
Pyruvate
Acetyl CoA
TPP PDH
TCA
TPP
Citrate
Oxaloacetate
α- Ketoglutarate
α- Ketoglutarate
dehydrogenase
Succinyl CoA
Ribose - 5P
Transketolase
TPP
Seduheptulose - 7P
Xylulose - 5P
Glyceraldehyde - 3P

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

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