Vit B1

Introduction
• Thiamine pyrophosphate is the active form of
vit B1 thiamine
• THYMINE is the base present in DNA
• THIAMINE is the vitamin B1
• Also known as anti beriberi factor
• Anti neuritis
• is involved in carbohydrate, fat, amino acid,
glucose, and alcohol metabolism.
 Introduction
• is required as a coenzyme in enzymatic
reactions that involve the transfer of an
aldehyde group.
 Chemistry
• Thiamine contains a substituted pyrimidine
ring connected to a substituted thiazole ring
by means of methylene bridge
• The vitamin is then converted to its active co-
enzyme form by addition of two phosphate
groups, with the help of ATP. The alcohol (OH)
group of thiamine is esterified with phosphate
to form thiamine pyrophosphate
• It is catalyzed by thiamin pyrophospho
transferase.
 Sources
• Whole wheat flour, unpolished rice, beans,
nuts and yeast are the good sources of
thiamine
• It is also present in liver, meat and eggs.
• Occurrence: It is present in large amounts in
skeletal muscle, heart, liver, kidney, and brain.
• It has a widespread distribution in foods, but
there can be a substantial loss of thiamine
during cooking above 100°C
• The body can only store up to 30 mg of
thiamine in its tissues.
 Recommended daily Allowance of
thiamine
• RDA is 1-1.5 mg/day
• Requirement increases with-
– increased carbohydrate intake
– Pregnancy
– Lactation
– Smoking
– Alcoholism
– Prolonged antibiotic intake
– Serious or prolonged illness
 Physiological Role of Thiamine
• i. Pyruvate dehydrogenase: Thiamine
pyrophosphate is an essential cofactor for
enzymes that catalyze the oxidative
decarboxylation of α-keto acids to form an
acylated coenzyme A (acyl CoA).
• These include pyruvate dehydrogenase , α -
keto glutarate dehydrogenase and branched-
chain α-keto acid dehydrogenase. These three
enzymes operate by a similar catalytic
mechanism.
• The pyruvate dehydrogenase complex is a large,
highly integrated complex of three kinds of
enzymes; Pyruvate dehydrogenase, dihydrolipoyl
transacetylase and Dihydrolipoyl dehydrogenase.
• At least two additional enzymes regulate the
activity of the complex and five coenzymes:
thiamine pyrophosphate (TPP), lipoic acid,
CoASH, FAD and NAD+ participate in the overall
reaction.
 Simplest
• 1. Pyruvate dehydrogenase: The co-enzyme
form is thiamine pyrophosphate (TPP). It is
used in oxidative decarboxylation of alpha
keto acids, e.g. pyruvate dehydrogenase
catalyzes the breakdown of pyruvate, to acetyl
CoA and carbon dioxide
• 2. Alpha ketoglutarate dehydrogenase: An
analogous biochemical reaction that requires
TPP is the oxidative decarboxylation of alpha
ketoglutarate to succinyl CoA and CO2 (citric
acid cycle )
• 3.Transketolase: The second group of enzymes
that use TPP as co-enzyme are the
transketolases, in the hexose monophosphate
shunt pathway of glucose
 Detail of point 3
• 3. Thiamine pyrophosphate is also an
important cofactor for the Transketolase
reactions in the pentose phosphate pathway
of carbohydrate metabolism
• 3. These reactions are important in the
reversible transformation of pentoses into the
glycolytic intermediates fructose 6-phosphate
and glyceraldehyde 3-phosphate
• 4. TPP plays an important role in the
transmission of nerve impulse. lt is believed
that TPP is required for acetylcholine synthesis
and the ion translocation of neural tissue
Deficiency Manifestations of Thiamine
• Beriberi: Deficiency of thiamine leads to
beriberi. It is a Singhalese word, meaning
"weakness". The early symptoms are anorexia,
dyspepsia, heaviness and weakness. Subjects
feel weak and get easily exhausted
• Wet beriberi: Here cardiovascular
manifestations are prominent. Edema of legs,
face, trunk and serous cavities are the main
features. Palpitation, breathlessness and
distended neck veins are observed. Death
occurs due to heart failure
• Dry beriberi: In this condition, CNS
manifestations are the major features.
Walking becomes
difficult. Peripheral neuritis with sensory
disturbance leads to complete paralysis
•
Biochemical changes in deficiency