A comprehensive presentation on Thiamine and biochemical aspects of Beriberi for MBBS, BDS, B Pham and Biotechnology students to facilitate easy leaning.

1. Thiamine (vitamin B 1) and biochemical aspects of
its deficiency manifestations- Beriberi
: water soluble vitamins (B complex group)
Dr. Rohini C Sane

2. Classificationofvitamins

3. Twelve Members of vitamin B complex
1. B1- Thiamine
2. B2- Riboflavin
3. B3- Niacin
4. B6- Pyridoxine
5. B12- Cyanocobalamin
6. B9 - Folic Acid 
7. Para amino benzoic acid
8. B5 -Pantothenic acid
9. Lipoic acid
10. B7- Biotin 
11. Choline 
12. Inositol  ( F, P, P,L  B C I)
grouped together because all of them function
as coenzymes in the human cells.

4. Properties of B complex vitamins
1. Water soluble
2.Yellow colored
3. Function as Coenzymes
4.Synthesized by gastrointestinal bacteria
5. Non toxic

5. Dietary Sources of B complex vitamins
a. Germinating seeds
b . Aleurone layer of cereals ( food grains –e.g. rice ,wheat )
c. wheat germ
d. Pulses
e. beans
f. Fruits
g. Yeast
h. Liver
i. Meat
j. Egg

6. ❖ Aleurone layer of cereals is rich source of Thiamine.
❖ When grains are polished , aleurone layer of cereals is removed .
❖ Whole wheat flour and unpolished rice have better nutritive value than completely
polished refined food .
Aleurone layer of cereals as dietary source of B complex vitamins

7. Recommended daily allowance (RDA) of B complex vitamins
B complex vitamin Recommended daily allowance of B complex( adults)
B1 -Thiamine 1.0-1.5 mg
B2- Riboflavin 1.5 mg
B3- Niacin 20 mg
B6- Pyridoxine 2 mg
B12- Cyanocobalamin 1.0 microgram
B9 - Folic Acid 100 microgram
Para amino benzoic acid 10 mg
B5 -Pantothenic acid 10 mg
B7- Biotin 200 micrograms
Choline Synthesized in human body by intestinal bacteria
(400mg)

8. ConditionsassociatedwithincreasedofDietary requirementofB
complexvitamins
Requirement of B complex vitamins increases during :
1.Pregnancy
2. Lactation
3.Increased calorie intake
4.Convalescence
5.Acute illness
6. Injury
7.Infection
8. Burns

9. Vitamin Coenzyme form Major Functions
Thiamine –B1 Thiamine pyrophosphate- TPP Carbohydratemetabolism,Oxidative
Decarboxylationofalphaketoacids
Riboflavin-B2 Flavin monophosphate- FMN
Flavin adenine dinucleotide -FAD
Oxidation ,reduction reactions
Oxidized in ETC (1.5 ATP)
Nicotinic acid B3 Nicotinic adenine dinucleotide -
NAD+ Nicotinic adenine dinucleotide
Phosphate -NADP+
Oxidation ,reduction reactions
Oxidized in ETC (2.5ATP),
hydroxylation reactions
PantothenicacidsB5 Coenzyme A - CoA Fattyacidssynthesis–fattyacidCoA
Pyridoxine –B6 Pyridoxal ,pyridoxamine, Pyridoxine Amino group transfer
Biotin- B7 Biocytin CO2 transfer
Folic acid -B9 Tetra hydro folic acid FH4 1-C transfer
Cyanocobalamin-
B12
methyl cobalamin ,Deoxy adenosyl
cobalamin
IsomerizationofmethylmalonylCoA,
methylationofhomocysteine
Coenzyme forms and Functions of Vitamin B complex

10. Biochemical manifestations of Vitamin B complex deficiency
❖Biochemical manifestations of Vitamin B complex deficiency include
decreased
• rate of TCA
• amino acid synthesis
• protein biosynthesis impaired anabolism in the human body.
• lipid synthesis
• gluconeogenesis
❖ This leads to Inadequate growth, Loss of weight , strength and apathy (due
to decreased ATP synthesis).

11. Generalized Deficiency manifestations of vitamin B complex
1. Inadequate growth
2. Loss of weight & strength (due to decreased ATP synthesis)
3. Microcytic ,Hypochromic anemia (as availability of succinyl CoA decreases
→decreased heme synthesis )
4. Neurological manifestations include
a) Loss of memory (amnesia)
b) Apathy
c) Numbness ( pins and needles sensation in legs)
Neurological manifestations due to
a) decreased availability of acetyl CoA and NADPH leading to decreased fatty
acid synthesis.
b) Decreased Trp- pyrrolase activity resulting in decreased synthesis of
neurotransmitter Acetyl choline ( in Kynurenine pathway Trp is oxidized
Kynurenine which converted to Acetyl CoA or niacin. Acetyl CoA is a precursor
for Acetyl choline synthesis ).

12. Vitamin Deficiency manifestations
Thiamine –B1 Beriberi,Wernicke- Korsakoff syndrome
Riboflavin-B2 Cheilosis , Angular stomatitis, glossitis , ,dermatitis ,photophobia
Nicotinic acid B-3 Pellagra
Pantothenic acids -B5 Burning feet syndrome
Pyridoxine –B 6 Epileptic convulsions , dermatitis , hypochromic microcytic anemia
Biotin- B7 Dermatitis
Folic acid -B9 Macrocytic Megaloblastic anemia ,Hyperhomocysteinemia
Cyanocobalamin - B12 Pernicious and Megaloblastic anemia, methyl malonic aciduria,
neuropathy
Specific Deficiency manifestations of Vitamin B complex

13. Sulphur containing vitamins
Sulphur containing vitamins are
1. Thiamine
2. Pantothenic acids
3. Lipoic acids
4. Biotin

14. Thiamine=Vitamin B1=Antiberiberi factor
=Aneurine = Antineuritis

15. Structure and chemistry of Thiamine
❖Adolf Windaus (Noble 1928)- elucidated structure of thiamine.
Thiamine contains a substituted pyrimidine ring connected to a
substituted Thiazole ring by means of methylene bridge.
▪ Christian Eijkman (Noble 1929)- produced Beriberi in chicken by
feeding polished rice.
• Thiamine ( Vitamin B1)  Thymine (is base present in DNA)
• Active form of Thiamine is Thiamine Pyrophosphate (TPP).
Thiamine + ATP → Thiamine Pyrophosphate (TPP)+ AMP (catalyzed by
TPP transferase in the jejunal mucosa)

16. Structure and chemistry of Thiamine

17. Activation of Thiamine to Thiamine phosphate
ActivationofThiaminetoThiaminephosphate(TPP)iscatalyzedbyThiaminepyrophosphatetransferase
whichtransfers twophosphategroupsofATPinthejejunalmucosa.
 
substitutedThiazolering
methylene bridge


substituted pyrimidine ring

18. Properties of Thiamine (vitamin B1 )
❖Properties of Thiamine (vitamin B1 ) :
1. Water soluble
2. Yellow colored
3. Function as a Coenzymes
4. Synthesized by gastrointestinal bacteria
5. Non toxic
6. Stable in the acid medium
7. Destroyed in an alkaline medium even at room temperature and by
improper cooking .
8. Cleaved into pyrimidine and thioazole half at pH 5 in sodium bisulphite
solution
9. oxidized with potassium ferricyanide in alkaline solution to thiochrome
which has a strong fluorescence ( estimation of Thiamine using
fluorometry)
10. Destroyed when autoclaved at 120 C for 30 minutes.

19. Dietary Sources of Thiamine

20. Recommended dietary allowance (RDA)of Thiamine (vitamin B1)
Category Recommended dietary allowance of Thiamine
(vitamin B1)
Adults 1.0 - 1.5 mg /day ( 0.5 mg/1000 Cal)
Children 0.7 -1.2 mg /day
Pregnant and lactating 2 mg /day
Old age and alcoholics 2 mg /day
Therapeutic doses : 5 – 20 mg of Thiamine daily have been proved to be beneficial .
Thiamine requirement is related to energy metabolism and therefore are expressed
in terms of energy.

21. Metabolism of Thiamine /Vitamin B 1/ Antiberiberi factor/ Antineuritis
Metabolism of Thiamine :
1. Absorption of Thiamine in the small intestine:
➢ Dietary Thiamine is readily absorbed in the small intestine by a carrier
mediated active transport process as long as intake is less than 5mg/day .
At higher intake levels passive diffusion contributes to its absorption.
➢ It is then phosphorylated to its active form TPP in the jejunal mucosa
by enzyme thiamine pyrophosphate transferase .
➢ Thiamine is carried by portal blood to the liver after its absorption..
2. Thiamine occurs in the free form the blood and its coenzyme form TPP
predominates in the cellular component.
3. No storage of Thiamine in human body therefore its regular supplies
needed in diet to maintain blood levels .
4. 10% excretion in urine along with its several catabolites .

22. Coenzyme role of Thiamine Pyrophosphate
❖Thiamine is required mainly for carbohydrate metabolism.
❖Thiamine in the form of its coenzyme Thiamine Pyrophosphate is
involved in the following enzymatic reactions :
1 . Oxidative decarboxylation in
a) Pyruvate dehydrogenase complex
b) Alpha ketoglutarate dehydrogenase complex
c) Alpha Keto Acid Dehydrogenase complex of branched chain alpha keto
acids of Valine ,Leucine, Isoleucine )
2. Transketolation by Transketolases in hexosemonophosphatepathway/shunt
ofGlucose

23. Pyruvate Dehydrogenase Complex
❖ Pyruvate Dehydrogenase Complex has three enzymes :
1. Pyruvate Dehydrogenase
2. Dihydrolipoyl Dehydrogenase
3. Dihydrolipoyl Transacetylase
❖ Pyruvate Dehydrogenase Complex has five coenzymes :
1) TPP 
2) FAD
3) NAD+
4) CoA SH
5) Lipoic acid
❖Pyruvate Dehydrogenase Complex uses Magnesium (Mg 2+) as a
cofactor.

24. Biochemical Functions of Thiamine :1
Pyruvate Dehydrogenase catalyzes oxidative decarboxylation of Pyruvate to Acetyl CoA (used
in TCA) and carbon dioxide. TPP functions as a coenzyme in this reaction.( cocarboxylase )
Coenzyme role of TPP in Pyruvate Dehydrogenase Complex


25. Role of Thiamine in Neural functions via Acetyl CoA
❖TPP is a coenzyme for Pyruvate Dehydrogenase Complex which catalyzes oxidative decarboxylation
of Pyruvate to Acetyl CoA and carbon dioxide.
❖ Acetyl CoA is involved in synthesis of :
1. Intermediates of TCA cycle → ATP ( essential for brain )
2. Neurotransmitter acetyl choline
3. Cholesterol ( as an insulating cover of nerve fibers for transmission of electrical impulses in the nervous
tissue )
4. Fatty acid ( Docosa-hexanoic acid DHA 3- cervonic acid is needed for development of brain,
sulphogalactoceramide found in myelin )
5. N- acetylneuraminic acid →constituent of ganglioside ( found on the nerve endings for binding of
neurotransmitters during neve impulse transmission )
6. Myelin (sphingomyelins are important constituent of brain and nervous tissue )
7. Acetylated amino sugars (N-acetylglucosamine, N-acetyl galactosamine are needed to prevent mental
retardation – mucopolysaccharidoses )
8. N-acetyl glutamate (NAG) in urea biosynthesis (needed to prevent toxic effects of ammonia on brain )
9. Glucose (brain tissue normally uses glucose as an exclusive fuel except during starvation . Human
brain needs 120 gm /day out of 160 gm needed by entire body for continuous supply of energy .Acetyl
CoA is activator of pyruvate carboxylase and promotes gluconeogenesis during starvation. )
10. Acetic acid (Acetyl CoA is active form of Acetic acid which is involved in conjugation of isoniazid during
Xenobiotic metabolism. Failure of this reaction leads to psychosis in tuberculosis patients
➢ Conclusion : Thiamine and Acetyl CoA are required for the normal functioning of the nervous system.

26. Impaired function of Pyruvate Dehydrogenase Complex in Thiamine
deficiency
❖Impaired function of Pyruvate Dehydrogenase Complex In Thiamine
deficiency have following biochemical consequences :
➢Decreased Pyruvate Dehydrogenase Activity( impairment in
conversion of Pyruvate to Acetyl CoA ) → Increased plasma Pyruvate
concentration and its excretion in urine. Accumulation of Pyruvate
occurs in tissues which is harmful.
➢ Normally Pyruvate does not cross the blood brain barrier and enter
the brain. However, in Thiamine deficiency ,alteration occurs in the
blood brain barrier permitting Pyruvate to enter the brain directly .
➢Pyruvate accumulation in brain results in its disturbed metabolism
and may be responsible for polyneuritis.
➢Lactic acidosis (Increased plasma Pyruvate concentration→ Increased
plasma lactate concentration )

27. Coenzyme role of TPP in Alpha ketoglutarate dehydrogenase complex
Alpha ketoglutarate dehydrogenase catalyzes oxidative decarboxylation of Alpha ketoglutarate to
succinyl CoA and carbon dioxide (in TCA).TPP functions as a coenzyme in this reaction( cocarboxylase ).
Biochemical Functions of Thiamine :2


28. Impaired functionof Alpha ketoglutarate dehydrogenase complex in
Thiamine deficiency
❖TPP is a coenzyme for Alpha ketoglutarate dehydrogenase which
catalyzes oxidative decarboxylation of Alpha ketoglutarate to succinyl CoA
and carbon dioxide (in TCA).
❖Impaired function of Alpha ketoglutarate dehydrogenase Complex in
Thiamine deficiency have following biochemical consequences :
a) Malfunctioning of TCA ( defective energy metabolism)
b) Microcytic ,Hypochromic anemia (as the availability of succinyl CoA
decreases →decreased heme synthesis ).

29. Microcytic ,Hypochromic anemia due Impaired function of Alpha
ketoglutarate dehydrogenase Complex in Thiamine deficiency
❖Impaired function of Alpha ketoglutarate dehydrogenase Complex in Thiamine deficiency have
following biochemical consequences :
a) Malfunctioning of TCA ( defective energy metabolism)
b) Microcytic ,Hypochromic anemia (as the availability of succinyl CoA decreases →decreased heme
synthesis ).

30. CoenzymeroleofTPPwithTransketolasesin hexosemonophosphateshuntofGlucose:1
TPP
Biochemical Functions of
Thiamine :3
Transketolase catalyzes the transfer of two carbon moiety from xylose 5 –phosphate to ribose 5-phosphate
to give 3 carbon Glyceraldehyde 3-phosphate and 7 carbon sedoheptulose 7-phosphate. TPP functions
as a coenzyme in this reaction.
.

31. Function of TPP with Transketolases in hexose monophosphate
shunt of Glucose for synthesis of fatty acids and nucleic acids
Hexose monophosphate shunt of Glucose is involved in synthesis of ribose 5 phosphate (synthesis of
nucleic acids )and NADPH (synthesis of fatty acids ,steroids ,neurotransmitters ,reduced glutathione)

32. Impaired activity of TPP dependent transketolases leads to neurological
manifestations
• In Thiamine deficiency ,the activity of TPP dependent transketolases in
hexose monophosphate shunt of Glucose is impaired .
• Impaired activity of TPP dependent transketolases results in impaired
synthesis of ribose 5 phosphate (hence impaired synthesis of nucleic
acids )and NADPH (impaired synthesis of fatty acids ,steroids,
neurotransmitters ,reduced glutathione) .
➢Impaired activity of TPP dependent transketolases leads to neurological
manifestations.

33. Coenzyme role of TPP in Alpha Keto Acid Dehydrogenase complex of
branched chain alpha keto acids :1
(uses coenzymes –TPP , NAD+, FAD, Lipoic acid and Mg 2 +as a cofactor )
Biochemical Functions of Thiamine :4

34. ❖branched chain alpha keto acids of Valine ,Leucine, Isoleucine are .
 ketoisovalerate,  ketoisocaproate ,  keto - -methyl valerate
( corresponding ketoacids of Valine ,Leucine, Isoleucine )
+
Alpha Keto Acid Dehydrogenase complex
(uses coenzymes –TPP , NAD+, FAD, Lipoic acid and Mg 2 +as a cofactor )
Transfer of activated CHO group to Alpha Lipoic Acid
Isobutyryl CoA , isovaleryl CoA ,  methylbutyryl CoA → synthesis of Acetyl CoA
( corresponding  ,  unsaturated acyl CoA thioesters) or succinyl CoA
Coenzyme role of TPP in Alpha Keto Acid Dehydrogenase complex of
branched chain alpha keto acids :2
Alpha Keto Acid Dehydrogenase catalyzes oxidative decarboxylation of ketoacids to , unsaturated
acyl CoA thioesters and carbon dioxide .TPP functions as a coenzyme in this reaction.

35. Neurological manifestations related to Thiamine deficiency and
impaired function of Alpha Keto Acid Dehydrogenase complex
• Branched chain amino acids viz Valine ,Leucine, Isoleucine undergo
transamination reaction to corresponding branched chain alpha keto
acids  ketoisovalerate,  ketoisocaproate ,  keto - -methyl valerate.
  ketoisovalerate (for synthesis of succinyl CoA),  ketoisocaproate
(for synthesis of Acetyl CoA ) and  keto - -methyl valerate (for
synthesis of succinyl CoA and Acetyl CoA ) are later converted by Alpha
Keto Acid Dehydrogenase complex which uses TPP as a coenzyme. .
• In Thiamine deficiency , the activity of Alpha Keto Acid Dehydrogenase
complex is impaired .This results in accumulation of Valine ,Leucine,
Isoleucine and their corresponding branched chain alpha keto acids in
blood ,urine CSF ( condition similar to maple syrup urine).
• In Thiamine deficiency ,synthesis of Acetyl CoA is impaired through
this pathway , this leads to neurological manifestations . Impaired
synthesis of succinyl CoA and heme leads to hypochromic anemia.

36. Thiamine deficiency and impaired cellular functions
• Thiamine deficiency leads to failure of carbohydrate metabolism
,resulting in deceased production of ATP and impaired cellular
functions of central nervous system ( peripheral nerves and
brain),heart and gastrointestinal tract.
• The overall picture of thiamine deficiency including cardiovascular,
neurological and gastrointestinal disorders is referred as Beriberi.

37. Cardio vascular manifestations in Thiamine deficiency
• Cardio vascular manifestations in Thiamine deficiency are
1. Palpitation/increase in heart rate (tachycardia)
2. enlargement of heart ( cardiomegaly, Hypertrophy)
3. Dilatation
4. Cardiac failure
5. Edema

38. Cardiac failure in Thiamine deficiency
Thiamine deficiency
failure of carbohydrate metabolism ,resulting in deceased production of ATP
Demand for oxygen supply by peripheral tissue for synthesis of ATP(through
biological oxidation involving ETC and oxidative phosphorylation )
Palpitation/increase in heart rate (→tachycardia) to fulfil increased oxygen
demand by the peripheral tissue
Enlargement of heart ( cardiomegaly, Hypertrophy , heart is a muscle )
Vein efforts of heart for oxygen supply to peripheral tissue due to microcytic, Hypochromic
anemia (as availability of succinyl CoA decreases →decreased heme synthesis )
Cardiac failure → impaired renal glomerular filtration → Edema

39. Cyanosis due to Cardiac failure in Thiamine deficiency
Thiamine deficiency → microcytic, Hypochromic anemia (as availability of
succinyl CoA decreases →decreased heme synthesis ) and increased oxygen
consumption /demand by peripheral tissue→ Cyanosis

40. Edema observed in Cardiac failure in Thiamine deficiency
❖ Cardio vascular manifestations in Thiamine deficiency:
Thiamine deficiency →Cardiac failure →impaired renal glomerular filtration →
Edema

41. Neurological manifestations in Thiamine deficiency
❖Neurological manifestations in Thiamine deficiency include :
a. anxiety
b. mental confusion
c. motor and sensory neuropathy ( Wernicke ’s encephalopathy )
d. peripheral neuritis
❖Neurological manifestations in Thiamine deficiency are due to
1. decreased availability of acetyl CoA and NADPH resulting in decreased fatty acid
,cholesterol synthesis.
2. Decreased Tryptophan pyrrolase activity resulting in decreased synthesis of
neurotransmitter Acetyl choline ( in Kynurenine pathway Trp is oxidized Kynurenine by
Tryptophan pyrrolase using TPP as a coenzyme . Kynurenine is then converted to
Acetyl CoA or niacin. Acetyl CoA is a precursor in Acetyl choline synthesis . )
3. decreased transketolase activity (resulting in impaired synthesis of NADPH hence
impaired synthesis of fatty acids ,steroids ,neurotransmitters , reduced glutathione).

42. Role of Thiamine in Neural functions via Acetyl CoA
❖TPP is a coenzyme for Pyruvate Dehydrogenase Complex which catalyzes oxidative decarboxylation
of Pyruvate to Acetyl CoA and carbon dioxide.
❖ Acetyl CoA is involved in synthesis of :
1. Intermediates of TCA cycle → ATP ( essential for brain )
2. Neurotransmitter acetyl choline
3. Cholesterol ( as an insulating cover of nerve fibers for transmission of electrical impulses in the nervous
tissue )
4. Fatty acid ( Docosa-hexanoic acid DHA 3- cervonic acid is needed for development of brain,
sulphogalactoceramide found in myelin )
5. N- acetylneuraminic acid →ganglioside ( found on the nerve endings for binding of neurotransmitters
during neve impulse transmission )
6. Myelin (sphingomyelins are important constituent of brain and nervous tissue )
7. Acetylated amino sugars (N-acetylglucosamine, N-acetyl galactosamine are needed to prevent mental
retardation – mucopolysaccharidoses )
8. N-acetyl glutamate (NAG) in urea biosynthesis (needed to prevent toxic effects of ammonia on brain )
9. Glucose (brain tissue normally uses glucose as an exclusive fuel except during starvation . Human
brain needs 120 gm /day out of 160 gm needed by entire body for continuous supply of energy .Acetyl
CoA is activator of pyruvate carboxylase and promotes gluconeogenesis during starvation. )
10. Acetic acid (Acetyl CoA is active form of Acetic acid which is involved in conjugation of isoniazid during
Xenobiotic metabolism. Failure of this reaction leads to psychosis in tuberculosis patients
➢ Conclusion : Impaired Acetyl CoA synthesis in Thiamine deficiency leads to neurological manifestations.

43. Gastrointestinal manifestations in Thiamine deficiency
In thiamine deficiency , impaired cellular functions of the
gastrointestinal tract leads to impaired absorption ,digestion
,constipation and anorexia (loss of appetite ) .

44. Beriberi : Deficiency manifestation of Thiamine
❖Deficiency manifestation of Thiamine→ Beriberi (Singhalese word meaning
weakness/ I cannot ) .
❖ Beriberi has
a. Cardiovascular manifestations
b. Neurological manifestations
c. Gastrointestinal symptoms
❖Types of Beriberi
a) Wet beriberi ( seen when Thiamine deficiency is severe)
b) Dry beriberi ( occurs in chronic dietary deficiency of Thiamine)
c) Infantile beriberi (occurs in infants born to mothers suffering Thiamine
Deficiency)
d) Wernicke- Korsakoff syndrome - cerebral Beriberi (seen in alcoholics with
chronic deficiency of Thiamine )
❖Polyneuritis

45. Wet beriberi : Deficiency manifestation of Thiamine
❖ Wet beriberi seen when Thiamine deficiency is severe.
❖Cardio vascular manifestations of wet beriberi
1. increase in Pulse , palpitation and Heart rate ( tachycardia)
2. Heart becomes weak
3. Breathlessness
4. Edema of legs ,face ,trunk and serous cavity
5. Dilatation , enlargement of the heat ( cardiomegaly )
6. Death occurs due to cardiac /heart failure
❖ Neurological manifestation (due to decreased transketolase activity) :
a. anxiety
b. mental confusion
c. motor and sensory neuropathy ( Wernicke ’s encephalopathy )
d. peripheral neuritis

46. Edema and cardiomegaly in Wet beriberi as a
deficiency manifestation of Thiamine
Edema Enlargement of the heat ( cardiomegaly )

47. Dry beriberi : Deficiency manifestation of Thiamine
Dry beriberi occurs in chronic dietary deficiency of Thiamine (diet chronically contains
slightly less than daily dietary requirement of Thiamine) .
❑Manifestation of Dry beriberi :
❖anorexia (loss of appetite )
❖loss of weight
❖Muscular weakness ,Muscle wasting ( walking becomes difficult due to increased
concentration of pyruvic acid & lactic acid)
❖Neurological manifestation (due to decreased transketolase activity is a major feature)
include :
a. Anorexia
b. anxiety
c. mental confusion
d. Muscle weakness and wasting →loss of weight
e. motor and sensory neuropathy ( Wernicke ’s encephalopathy )
f. peripheral neuritis

48. Symptoms of Dry beriberi : Deficiency manifestation of Thiamine

49. Infantile beriberi
❖Infantile beriberi occurs in infants born to mothers suffering thiamine
deficiency. The breast milk of mothers of these infants contains low thiamine
content .
❖Symptoms of Infantile beriberi:
1. Restlessness
2. Sleeplessness
3. Anorexia
4. Vomiting
5. Convulsions
6. Edema
7. Tachycardia , Bouts of screaming due to cardiac dilatation
8. Aphonia (absences or loss of voice)
9. If not treated ,death

50. Infantile beriberi

51. Wernicke-Korsakoff syndrome: Cerebral Beriberi
Wernicke- Korsakoff syndrome (seen in alcoholics with chronic deficiency of
Thiamine). It is also called a cerebral Beriberi .
Although this syndrome occurs in alcoholics ,it may arise secondary to any disorder
which impairs nutrition.

52. Wernicke-Korsakoff syndrome: Deficiency manifestations
of Thiamine

53. Wernicke-Korsakoff syndrome: Deficiency manifestations
of Thiamine

54. Wernicke-Korsakoff syndrome: Deficiency manifestations of Thiamine
❖ Wernicke- Korsakoff syndrome (seen in alcoholics with chronic deficiency of Thiamine ). It
is also called a cerebral Beriberi .
❖Carl Wernicke (in 1984) and Sergei Sergeivich Korsakoff (in 1987) described this condition
❖ Gastrointestinal symptoms in Wernicke- Korsakoff syndrome are due to
1. Insufficient intake and Impaired Gastrointestinal absorption of diet including Thiamine in
alcoholics (intestinal epithelium is disintegrated in alcoholism)
2. Increased human body demands for diet including Thiamine in Alcoholism
3. Alcohol inhibits intestinal absorption of Thiamine.
❖ Neurological manifestation (due to decreased transketolase activity)
include Encephalopathy ( Ophthalmoplegia- paralysis of extraocular ,iris , ciliary
muscles→ loss of paired movement of eyes → double vision , Nystagmus- Rapid back and
forth involuntary movements of eyes, Ataxia- defective muscular coordination →shaky
movements ),hemorrhagic lesions of the third and forth ventricle of the brain ,
anorexia ,muscular weakness, peripheral paralysis, Apathy .
If not treated ,it progresses to Korsakoff ’s psychosis which is irreversible and characterized
by loss of memory of recent events, mental confusion, inability to retain new information.

55. Characteristics of Neurological manifestations of Wernicke-Korsakoff
syndrome
Characteristics of Neurological manifestations Wernicke-Korsakoff syndrome include :
➢ Symmetrical lesions in various parts of the brain stem, diencephalon and cerebellum
➢ The areas commonly affected being the mammillary bodies ,the nuclei of the thalamus and
periaqueductal grey matter
➢ Destruction of myelin with less damage to neurons in Wernicke-Korsakoff syndrome
➢ Hemorrhagic lesions of the third and forth ventricle of the brain (not always present)

56. Wernicke ’s encephalopathy
Neurological manifestation of (due to decreased transketolase activity) include
❖ Encephalopathy : generalized brain dysfunction
1. Ophthalmoplegia- paralysis of extraocular ,iris , ciliary muscles→ loss of paired movement of eyes
→ double vision
2. Nystagmus- Rapid back and forth involuntary movements of eyes

57. Molecular basis of Dermatitis in Wernicke-Korsakoff syndrome
How Thiamine Deficiency leads to Dermatitis ( inflammation of skin)
1. Thiamine Deficiency → impaired cellular functions of the gastrointestinal tract leads to impaired absorption of
diet→ defective anabolism /repair mechanism in the human body → Dermatitis
2. Thiamine Deficiency → impaired synthesis of Acetyl CoA ,cholesterol ,fatty acids, glycoproteins→ fragile
plasma membrane of the skin cells→ Dermatitis
3. Thiamine Deficiency → failure of xenobiotic mechanism involving acetic acid(Acetyl CoA )→Toxicity of
xenobiotic on the skin cells → Dermatitis
4. Thiamine Deficiency → impaired anabolism in the human body → Dermatitis
Therapeutic doses : 5 – 20 mg of Thiamine daily have been proved to be beneficial .

58. Biochemical changes in Thiamine (Vitamin B1) deficiency:1
❖Biochemical changes in Vitamin B 1 deficiency include decreased
• rate of TCA
• amino acid synthesis
• protein biosynthesis impaired anabolism in the human body.
• lipid synthesis
• gluconeogenesis
❖ This leads to Inadequate growth, Loss of weight & strength (due to
decreased ATP synthesis).

59. Biochemical changes in Thiamine deficiency :2
➢Decreased Pyruvate Dehydrogenase Activity( impairment in conversion of Pyruvate to
Acetyl CoA ) → Increased plasma Pyruvate concentration and its excretion in urine.
Accumulation of Pyruvate occurs in tissues which is harmful.
➢ Normally Pyruvate does not cross the blood brain barrier and enter the brain.
However, in Thiamine deficiency ,alteration occurs in the blood brain barrier permitting
Pyruvate to enter the brain directly .
➢Pyruvate accumulation in brain results in its disturbed metabolism and may be
responsible for polyneuritis.
➢Lactic acidosis (Increased plasma Pyruvate concentration→ Increased plasma lactate
concentration )
❖Decreased Alpha Ketoglutarate dehydrogenase Activity→ Increased plasma Alpha
Ketoglutarate concentration
❑ Transketolase activity decreased → POLYNEURITIS
❑RBC Transketolase activity decreased ( earliest manifestation)
✓Branched chain ketoaciduria with poor activity of the keto acid dehydrogenase system

60. Erythrocyte Transketolase activity : a diagnostic test to assess
Thiamine deficiency.
• Measurement of whole blood /erythrocyte (RBC) Transketolase
activity is a diagnostic test to assess Thiamine deficiency.
❖Reference interval for transketolase activity :
Whole blood Transketolase activity = 9 -12 micromoles /hour/ml
( 150- 200 U/ L)
Erythrocyte Transketolase activity 0.75 – 1.30 U/ g of hemoglobin

61. Symptoms of wet ,dry and cerebral Beriberi

62. Thiamine deficiency due to Thiaminase and Pyrithiamine
❖Thiamine deficiency due to Thiaminase from sea food:
Thiamine
Thiaminase (sea food) hydrolysis of thiamine
Pyrimidine + Thiazole
➢ Beriberi is attributed to the consumption of a raw fish (rich in
Thiaminase) in some parts of Japan.
❖Thiamine deficiency due to Pyrithiamine from ferns :
Pyrithiamine is structural analogues / antagonist of Thiamine and inhibits
its activity .
➢Horses and cattle often develop Thiamine deficiency due overconsumption
of the plant fern ( fern poisoning).
❖Oxythiamine is also a structural analogues of Thiamine.

63. Polyneuritis : Deficiency manifestation of Thiamine
❖Polyneuritis may be associated with
a) Chronic alcoholics: Alcohol inhibits intestinal absorption of Thiamine .
Polyneuritis is common in chronic alcoholics .
b) Pregnancy: insufficient intake and increased requirement of diet
including Thiamine
c) Old age : insufficient intake of diet including Thiamine, Impaired
Gastrointestinal absorption of diet including Thiamine (epithelium is
disintegrated-degenerative changes )
d) Diabetes Mellitus
❖Thiamine supplementation is beneficial in Polyneuritis.
❖A Lipid soluble acylated derivative ( benfotiamine ) is recommended
to improve diabetic neuropathy. It decreases glycation of proteins
(AGE).

64. Deficiency manifestation of Thiamine in Diabetes Mellitus
❖Thiamine Deficiency → impaired synthesis of Acetyl CoA ,cholesterol ,fatty acids and
glycoproteins→ demyelination of nerve and damaged blood vessels → Diabetic peripheral
neuropathy →gangrene

65. Prevention of Beriberi
❖Beriberi can be prevented by
• use of home pounded or parboiled rice in diet
• Increased use of pulses , cereals and other food containing thiamine
• the establishment of more maternal and child health care centers to
deliver advice on the good diet practices in pregnancy and lactation
• Vitamin supplementation to infants , pregnant and lactating women

66. e