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Metabolism of Vitamin B1
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THIAMINE (B1]
Gandham. Rajeev
Department of Biochemistry,Akash Institute of Medical Sciences & Research Centre,Devanahalli, Bangalore, Karnataka, India.
E-Mail: [email protected]
Thiamine (B1)
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-CH2 - CH2 – O - P- O – P -
O
O O
O O
Pyrimidine ring
Methylene bridge
ThiazolePyrophosphat
e
CH3
Structure of TPP
Metabolism:
Absorption: Thiamin is carried by the portal
blood to the liver, present as free thiamine
Storage: Usually 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 Complex
NAD+
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
Oxaloacetate
α- 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/day
Deficiency :
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
Reference interval:
Whole blood:-9 to 12 µmol/hour/ml 150 to
200U/L
Erythrocyte :- 0.75 to 1.30 U/g of Hb
+ 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 waight
Muscles become weak & walking becomes
difficult
Mental confusion
Thiamine deficiency - Polyneuritis
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
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