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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]

Vitamin (B1)

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Metabolism of Vitamin B1

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Page 1: Vitamin (B1)

THIAMINE (B1]

Gandham. Rajeev

Department of Biochemistry,Akash Institute of Medical Sciences & Research Centre,Devanahalli, Bangalore, Karnataka, India.

E-Mail: [email protected]

Page 2: Vitamin (B1)
Page 3: Vitamin (B1)

Thiamine (B1)

Page 4: Vitamin (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

Page 5: Vitamin (B1)

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

Page 6: Vitamin (B1)

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

Page 7: Vitamin (B1)

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

Page 8: Vitamin (B1)

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

Page 9: Vitamin (B1)

Transketolase is dependent on TPP

It is involved in HMP shunt

Pyruvate

Acetyl CoA

PDH Complex

NAD+

NADH + H+ TPP

Page 10: Vitamin (B1)

α- Ketoglutarate dehydrogenase

complex:

It converts α- Ketoglutarate succinyl

CoA in TCA cycle

α-Ketoglutarate

Succinyl CoA

α- Ketoglutarate DH ComplexNAD+

NADH + H+

TPP

Page 11: Vitamin (B1)

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

Page 12: Vitamin (B1)

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

Page 13: Vitamin (B1)

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

Page 14: Vitamin (B1)

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

Page 15: Vitamin (B1)

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

Page 16: Vitamin (B1)

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

Page 17: Vitamin (B1)

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

Page 18: Vitamin (B1)

+ 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

Page 19: Vitamin (B1)

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

Page 20: Vitamin (B1)
Page 21: Vitamin (B1)

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

Page 22: Vitamin (B1)
Page 23: Vitamin (B1)

Thiamine deficiency - Polyneuritis

Page 24: Vitamin (B1)

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

Page 25: Vitamin (B1)

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

Page 26: Vitamin (B1)

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

Page 27: Vitamin (B1)

Antimetabolites

Thiaminase

It is present in raw fish & seafood

Thiaminase destroys thiamine if it is

present in the diet

Page 28: Vitamin (B1)

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

Page 29: Vitamin (B1)