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