Post on 18-Jan-2017
THIAMINE (B1]
Gandham. Rajeev
Department of Biochemistry,Akash Institute of Medical Sciences & Research Centre,Devanahalli, Bangalore, Karnataka, India.
E-Mail: gandhamrajeev33@gmail.com
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
SN -CH2 - CH2 – O - P- O – P -
O
O 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
Bio chemical functions
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
Transketolase is dependent on TPP It is involved in HMP shunt
Pyruvate
Acetyl CoA
PDH ComplexNAD
+NADH +
H+ TPP
α- Ketoglutarate dehydrogenase complex:
It converts α- Ketoglutarate succinyl CoA in TCA cycle
α-Ketoglutarate
Succinyl CoA
α- Ketoglutarate DH ComplexNAD+
NADH + H+
TPP
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
Glucose Glucose – 6 P
Pyruvate
Acetyl CoA
TPP PDH
TCA
TPP
Citrate
Oxaloacetateα- Ketoglutarate
α- Ketoglutarate dehydrogenase
Succinyl CoA
Ribose - 5P
TransketolaseTPP
Seduheptulose - 7P
Xylulose - 5P
Glyceraldehyde - 3P
Dietary sources
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
RDA
Adults - 1-1.5 mg/day Children - 0.7-1.2 mg/day Pregnancy & lactation - 2 mg/dayDeficiency :Causes: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
+ Clinical features
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
Cerebral beri-beri
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
Infantile beri-beri 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
Biochemical findings
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
AntimetabolitesThiaminase 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