Transcript Vitamin B1 Thiamin

Vitamin B1
Thiamin
Vitamin B complex
Vitamin B complex
Thiamin (anti – beriberi)
• Thiamin was first realized in the 1800s by
Eijkman, when it was discovered that fowl fed a
diet of cooked, polished (devoid of the outer
layers) rice developed neurologic problems (now
called beriberi).
• The substance initially called thiamine that
corrected the problems was first isolated from
rice bran in 1912 by Casmir Funk.
• The vitamin’s structure discovered by R. Williams
from the United States in 1930s.
structure
• Thiamin (vitamin B1) consists of a pyrimidine
ring and a thiazole moiety (meaning one of
two parts) linked by a methylene (CH2) bridge.
Sources
• Thiamin is widely distributed in foods,
including meat, legumes, and whole, fortified,
or enriched grain products, cereals, and
breads.
• Yeast, wheat germ, and soy milk also contain
significant amounts of the vitamin.
• In supplements, thiamin is found mainly as
thiamin hydrochloride or as thiamin
mononitrate salt.
Sources
Stability
• Thiamin is destroyed by prolonged heat.
• Food should be cooked in small amounts of water so
that thiamin and other water- soluble vitamins don’t
leach out.
• Baking soda should not be added to vegetable as it
breaks thiamin.
• Avoid sulfite preservatives as it breaks thiamin.
• Drinking tea with meal will decrease the amount of
thiamin that absorbed by the body.
• Vitamin B1 is stable in acid, unstable in aqueous
solutions of pH more than 5.
Digestion, absorption & transport
• In plants, thiamin exists in a free (nonphosphorylated)
form.
• In animal products, 95% of thiamin occurs in a
phosphorylated form, primarily thiamin diphosphate
(TDP), also called thiamin pyrophosphate (TPP).
• Intestinal phosphatases hydrolyze the phosphates from
the thiamin diphosphate prior to absorption.
Absorption
• Absorption of thiamin from foods is thought to be high.
• Antithiamin factors may be present in the diet. For example:
• Thiaminases present in raw fish catalyze the cleavage of thiamin,
destroying the vitamin.
• These thiaminases are thermolabile, so cooking fish renders the
enzymes inactive.
• Polyhydroxyphenols such as tannic and caffeic acids, which are
thermostable, are found in coffee, tea, betel nuts, and certain fruits
and vegetables such as blueberries, black currants, Brussels sprouts,
and red cabbage.
• These inactivate thiamin have an oxyreductive effect to inactivate
thiamine; this process facilitated by divalent minerals such as
calcium and magnesium.
• Thiamin destruction may be prevented, by presence of reducing
compounds such as vitamin C and citric acid.
Absorption
• Absorption of thiamin occurs primarily in the jejunum, with
lesser amounts absorbed in the duodenum and ileum.
• Free thiamin, not phosphorylated thiamin, is absorbed into
the intestinal mucosal cells.
• Yet, within the mucosal cells, thiamin may be
phosphorylated.
• Absorption of thiamin can be both active and passive,
depending on the amount of the vitamin presented in the
intestine for absorption.
Absorption
• When intakes of thiamin are high, absorption is
predominantly by passive diffusion.
• At low physiological concentrations, thiamin
absorption is active and is sodium-dependent.
• Two thiamin transporters from the SLC19 gene family
have been characterized; the protein carriers are called
ThTr1 and ThTr2. Both of these carriers are found in a
variety of tissues including the intestine and kidneys.
• Defects in the gene SLC19A2, which codes for ThTr1,
have been shown to cause thiamin deficiency
Transport
• Thiamin transport across the basolateral membrane occurs
by a thiamin/H1 antiport system.
• Ethanol ingestion, interferes with active transport of
thiamin from the mucosal cell across the basolateral
membrane, but not the brush border membrane.
• Thiamin in the blood is typically either in its free form,
bound to albumin, or found as thiamin monophosphate
(TMP). Most of thiamine exists as TDP.
• Most (~90%) of the thiamin in the blood is present within
• the blood cells.
Transport
• Another form of thiamin, thiamin triphosphate (TTP),
represents about 10% of total body thiamin.
• TTP is synthesized by action of a TDP-ATP phosphoryl
transferase that phosphorylates TDP.
• The terminal phosphate on the TTP may be hydrolyzed
by thiamin triphosphatase to yield TDP.
• TDP can be converted to TMP by thiamin
diphosphatase.
• TMP can be then converted to free thiamin by thiamin
monophosphatase.
Transport
• TTP, as well as TDP and TMP, can be found in
small
• amounts in several tissues, including the brain,
heart, liver, muscles, and kidney.
• TMP is thought to be derived from the catabolism
of the terminal phosphate on TDP and is believed
to be inactive.
• Enzymes responsible for thiamin phosphorylation
and dephosphorylation are found in a variety of
organs and tissues, including the brain.
FUNCTIONS AND MECHANISMS OF ACTION
• Thiamin plays essential coenzyme and
noncoenzyme roles in the body, including these:
• Energy transformation (a coenzyme role in crabs
metabolism, kreb’s cycle).
• Synthesis of pentoses and nicotinamide adenine
dinucleotide phosphate (NADPH) (also as a
coenzyme role).
• Membrane and nerve conduction (in a
noncoenzyme capacity).
Co- enzyme roles
• As TDP, thiamin functions in energy
transformation as a coenzyme of the pyruvate
dehydrogenase complex, the α-ketoglutarate
dehydrogenase complex, and the
branchedchain α-keto acid dehydrogenase
complex.
• In addition, TDP serves as a coenzyme for
transketolase needed for the synthesis of
NADPH and pentoses.
Energy Transformation
• Thiamin as TDP functions as a coenzyme necessary for the oxidative
decarboxylation of pyruvate, α-ketoglutarate, and the three
branched-chain amino acids isoleucine, leucine, and valine.
• These reactions are instrumental in generating energy (ATP).
• Inhibition of the decarboxylation reactions:
• pyruvate and α-ketoglutarate prevents synthesis of ATP and of the
acetyl CoA needed for the synthesis of, fatty acids, cholesterol, and
other important compounds.
• The inhibition also results in the accumulation of pyruvate, lactate,
and α-ketoglutarate in the blood.
Noncoenzyme Roles
• Membrane and Nerve Conduction
• Thiamin, as TTP, is thought to function in a
manner other than as a coenzyme.
• In nerve membranes, TTP is thought to
activate ion (specifically chloride) transport.
• Thiamin also may be involved in nerve impulse
transmission by regulation of sodium channels
and acetylcholine receptors.
METABOLISM AND EXCRETION
• Excess of thiamin of tissue needs and storage capacity
is excreted intact, as well as catabolized for urinary
excretion.
• Degradation of thiamin begins when the molecule is
cleaved into its pyrimidine and thiazole moieties.
• The two rings are then further catabolized, generating
20 or more metabolites .
• TDP and TMP are also excreted intact.
RECOMMENDED DIETARY ALLOWANCE
• The 1989 RDA for thiamin, the basis on studies
examining urinary excretion of thiamin, changes in
erythrocyte transketolase activity, and thiamin intake
data.
• For adult men
1.2 mg/d
• For adult women 1.1 mg/d
• For pregnancy
1.4 mg/d
• For lactation
1.5 mg/d
• The daily requirement increase with high carbohydrate
intake and for hard worker or athletes.
DEFICIENCY: BERIBERI
• Beriberi (beri means “weakness”).
• One of the first symptoms of thiamin
deficiency is a loss of appetite (anorexia) and
thus weight loss.
• As the deficiency worsens, cardiovascular
system involvement (such as hypertrophy and
altered heart rate) and neurological symptoms
(such as apathy, confusion, decreased shortterm memory, and irritability) appear.
DEFICIENCY: BERIBERI
• Three types of beriberi have been identified:
1. Dry beriberi found predominantly in older adults, is
thought to result from a chronic low thiamin intake with a
high carbohydrate intake. Characterized by muscle
weakness and wasting.
2. Wet beriberi cardiomegaly (enlarged heart), rapid heart
beat (tachycardia), rightside heart failure and peripheral
edema.
3. Acute beriberi seen mostly in infants, has been
documented in countries including Japan. Acute beriberi
is associated with anorexia, vomiting, lactic acidosis.
• Use of parenteral nutrition devoid of thiamin can cause
acute thiamin deficiency within a few weeks.
DEFICIENCY: BERIBERI
TOXICITY
• There appears to be little danger of thiamin
toxicity associated with oral intake of large
amounts (500 mg daily for 1 month) of thiamin.
• Excessive thiamin (100 X RDA) administered
intravenously or intramuscularly, associated with
headache, convulsions, cardiac arrhythmia, and
anaphylactic shock, among other signs.
• No tolerable upper intake level has been
established.