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THIAMINE (B1]
Shyam sundar yadav
Nims college of paramedical
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
 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
N
N
NH2
H3C
CH2
S
N
O O
-CH2 - CH2 – O - P- O – P - O
O O
Pyrimidine ring
Methylene bridge
Thiazole Pyrophosphate
CH3
Structure of
TPP
 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
 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
Acetyl CoA
 Transketolase is dependent on TPP
 It is involved in HMP shunt
Pyruvate
PDH Complex
TPP
NAD+
NADH + H+
 α- Ketoglutarate dehydrogenase
complex:
 It converts α- Ketoglutarate succinyl CoAin
TCA cycle
α-Ketoglutarate
Succinyl CoA
α- Ketoglutarate DH Complex
TPP
NAD+
NADH + H+
Corresponding Acyl CoA
 Essential for transmission of nerve impulse
 TPP is required for synthesis of Acetylcholine
NADH + H+
 The branched chain α-Keto acid
dehydrogenase (decarboxylase):
 It catalyses the conversion of α-keto acids to
corresponding acyl CoA
Branched chain α-Keto acid
NAD+
Branched chain α-Keto acid DH Complex
TPP
Glucose Glucose – 6 P
Pyruvate
Acetyl CoA
TPP PDH
TCA
TPP
Succinyl CoA
Citrate
Oxaloacetate
α- Ketoglutarate
α- Ketoglutarate
dehydrogenase
Ribose - 5P
Transketolase
TPP
Seduheptulose - 7P
Xylulose - 5P
Glyceraldehyde - 3P
 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
 Adults - 1-1.5 mg/day
 Children - 0.7-1.2 mg/day
 Pregnancy & lactation
Deficiency :
Causes:
- 2 mg/day
B1 deficiency is caused by inadequate
intake of thiamine in diet
 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
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
 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
 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
 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
 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
 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
 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
 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
 Antimetabolites
 Thiaminase
 It is present in raw fish & seafood
 Thiaminase destroys thiamine if it is present
in the diet
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
Thiamine.pptx

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Thiamine.pptx

  • 1. THIAMINE (B1] Shyam sundar yadav Nims college of paramedical
  • 2. 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
  • 3.  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
  • 4. N N NH2 H3C CH2 S N O O -CH2 - CH2 – O - P- O – P - O O O Pyrimidine ring Methylene bridge Thiazole Pyrophosphate CH3 Structure of TPP
  • 5.  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
  • 6.  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
  • 7. Acetyl CoA  Transketolase is dependent on TPP  It is involved in HMP shunt Pyruvate PDH Complex TPP NAD+ NADH + H+
  • 8.  α- Ketoglutarate dehydrogenase complex:  It converts α- Ketoglutarate succinyl CoAin TCA cycle α-Ketoglutarate Succinyl CoA α- Ketoglutarate DH Complex TPP NAD+ NADH + H+
  • 9. Corresponding Acyl CoA  Essential for transmission of nerve impulse  TPP is required for synthesis of Acetylcholine NADH + H+  The branched chain α-Keto acid dehydrogenase (decarboxylase):  It catalyses the conversion of α-keto acids to corresponding acyl CoA Branched chain α-Keto acid NAD+ Branched chain α-Keto acid DH Complex TPP
  • 10. Glucose Glucose – 6 P Pyruvate Acetyl CoA TPP PDH TCA TPP Succinyl CoA Citrate Oxaloacetate α- Ketoglutarate α- Ketoglutarate dehydrogenase Ribose - 5P Transketolase TPP Seduheptulose - 7P Xylulose - 5P Glyceraldehyde - 3P
  • 11.  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
  • 12.  Adults - 1-1.5 mg/day  Children - 0.7-1.2 mg/day  Pregnancy & lactation Deficiency : Causes: - 2 mg/day B1 deficiency is caused by inadequate intake of thiamine in diet
  • 13.  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
  • 14. 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
  • 15.  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
  • 16.  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
  • 17.  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
  • 18.
  • 19.  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
  • 20.  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
  • 21.  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
  • 22.  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
  • 23.  Antimetabolites  Thiaminase  It is present in raw fish & seafood  Thiaminase destroys thiamine if it is present in the diet
  • 24. 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