Vitamins

By
Nura Malahayati
THP-FP
UNSRI
 Introduction
 Casimir Funk (1884-1967) :
• Vitamines (amines required for life)
• Thiamin in rice polishing prevention cure of
beriberi
• In 1912, thiamin-containing extracts from rice
polishing, yeast, milk, and ox brain
• He claimed “the curative substance is a
pyrimidine base” (uracil and thymine)
• Produced “Oscodal” vitamin A and D
concentrate (the first vitamin preparation
accepted by the American Medical Association
as a product could be promoted as a source of
vitamin)
 Definition
 H.R. Rosenberg’s :
“Vitamins are essential organic
compounds needed only in minute
quantities in the diet but essential
for specific metabolic reactions
within the cell and necessary for
normal growth and maintenance
of health”
Classification (based on solubility)
 Discovered by McCollum “fat soluble A” (1913).
 The fat-soluble vitamins A, D, E, K bind to
ingested lipid and are absorbed along with their
digestion products.
 Anything that interferes with fat absorption will
affect uptake of fat-soluble vitamins.
 Except for vitamin K, fat-soluble vitamins are
stored in the body.
 Excesses may cause problems.
 Chemical composition: only C, H and O.
 Discovered by McCollum “water
soluable B” (1915).
 The water-soluble vitamins, B and C are
absorbed along with water from the
gastrointestinal tract (except for vitamin
B12 which must bind to gastric intrinsic
factor to be absorbed).
 Not stored and excess lost in urine.
 Chemical composition: C, H, O, N, S
and Co.
Water Soluble Vitamins
Thiamin (B1)
Structure

– pyrimidine ring
– thiazole ring
– methyl bridge
 Thiamin : vitamin form

Pyrimidine ring Thiazole ring

Thiamin pyrophosphate: coenzyme form

 Chemical
Characteristics
 Very labile nutrient
 Heat

– stable in crystalline form

– less stable in solution

 Alkali - very unstable with heat

– baking soda
 Chemical
Characteristics
 Sulfites
- decomposes B1
 High cooking/processing
losses
– heat
– leaching
 Absorption
 induodenum
 no significant storage,
excess to urine
 Biochemical Function
 The coenzyme thiamine
pyrophosphate or cocarboxylase is
intimately connected with the energy
releasing reactions in the carbohydrate
metabolism.
 Some of the reactions are dependent
on TPP, besides the other coenzyme.
 α-ketoglutrate dehydrogenase is an
enzyme of TCA cycle, this enzyme
require TPP.
 Transketolase is dependent on TPP. This is
an enzyme of hexose monophosphate
shunt (HMP).
 The branched chain α- keto acid dehydrogenase
(decarboxylase) catalyses the oxidative
decarboxylation of branched chain amino acids
(valine, leucine and isoleucine) to the respective
keto acids. This enzyme also require TPP.
 TPP plays an important role in the transmission
of nerve impulse.
 Recommended Dietary
Allowance
 The daily requirement of thiamine depends
on the intake of carbohydrate.
 A dietary supply of 1-1.5 mg/day is
recommended for adults (about 0.5
mg/1000 kcals of energy).
 For children RDA is 0.7-1.2 mg/day.

 The requirement marginally increases in

pregnancy (2 mg/day), lactation, old age
and alcoholism.
 Dietary Sources
 Cereals, pulses, oil seed, nuts and yeast are
good sources.
 Thiamine is mostly concentrated in the outer
layer (bran) of rice.
 Polishing of rice removes about 80% of
thiamine.
 Vitamin B1 is also present in animal food like
pork, liver, heart, kidney, milk etc.
 In the parboiled (boiling of paddy with husk) and
milled rice, thiamine is not lost in polishing, since
thiamine is a water soluble vitamin, it is
extracted into the water during cooking process.
Such water should not be discarded.
 Deficiency Symptoms

 The deficiency of vitamin B1 results in a

condition called beri-beri.
 Beri–beri is mostly seen in populations
consuming exclusively polished rice as
staple food.
 The early symptoms of thiamine deficiency
are loss of appetite (anorexia), weakness,
constipation, nausea, mental depression,
Peripheral neuropathy irritability etc.
 Numbness in the legs, complaints of pins
and needles sensation are reported.
Infantile Beri-Beri
 first
6 months
 breast milk deficient in B1

 Mother with or without symptoms

 rapid onset

 cyanosis, tachycardia, labored

breathing
 heart failure and death
 Wet Beri Beri
 symptoms similar to congestive
heart failure
 Pitting edema - trunk, limbs, face
 labored breathing, tachycardia
 rapid deterioration
 fatal circulatory collapse
 responds rapidly to B1
supplements
 Dry Beri-Beri
 no edema
 progressive wasting

 numbing and
weakening of
extremities
 chronic infections
 2000 RDA for Thiamin
Males Females
19-30yrs 19-30yrs
RDA mg/d 1.2 1.1

EAR 1.0 0.9

NHANES III 1.78 1.45

Mean intake
 Riboflavin (B2)

 Riboflavin through its coenzymes

takes part in a variety of cellular
oxidation reduction reaction.
 Chemistry

 Riboflavin contains 6,7 dimethyl

isoalloxazine (a hetercyclic 3 ring
sturcture) attached to D-ribitol by a
nitrogen atom.

 Ribitol is an open chain form of sugar

ribose with the aldehyde group (CHO)
reduced to alcohol (CH2OH).
 Riboflavin is stable to heat but sensitive
to light.
 When exposed to ultra-violet rays of
sunlight, it is converted to lumiflavin
which exhibits yellow fluorescents.
 The substances namely lactoflavin
(from milk), hepatoflavin (from liver)
and ovaflavin (from eggs) which were
originally thought to be different are
structurally identical to riboflavin.
 Coenzymes of Riboflavin
 Flavin mononucleotide (FMN) and flavin
adenine dinucleotide (FAD) are the two
coenzyme forms of riboflavin.
 The ribitol (5 carbon) is linked to
phosphate in FMN.
 FAD is formed from FMN by the transfer
of an AMP moiety from ATP.
 Biochemical Functions
 The flavin coenzymes (mostly FAD and to
a lesser extent FMN) participate in many
redox reactions responsible for energy
production.
 The functional unit of both the coenzymes
is isoalloxazine ring which serves as an
acceptor of two hydrogen atoms (with
electrons).
 FMN or FAD undergo identical reversible
reactions accepting two hydrogen atoms
forming FMNH2 or FADH2.
 Enzymes that use flavin coenzymes (FMN or
FAD) are called flavoproteins.
 The coenzymes (prosthetic groups) often bind
rather tightly, to the protein (apoenzyme) either
by non-covalent bonds (mostly) or covalent
bonds in the holoenzyme.
 Many flavoproteins contain metal atoms (iron,
molybdenum etc). Which are known as
metalloflavoproteins.
 The coenzymes FAD and FMN are associated
with certain enzymes involved in carbohydrate,
lipid, protein and purine metabolism, besides the
electron transport chain.
 Recommended Dietary Allowance

 The daily requirement of riboflavin for an

adult is 1.2-1.7 mg.

 Higher intakes (by 0.2-0.5 mg/day) are

advised for pregnant and lactating
women.
 Deficiency Symptoms

 Riboflavin deficiency symptoms include cheilosis

(fissures at the corners of the mouth), glossitis
(tongue smooth and purplish) and dermatitis.
 Riboflavin deficiency as such is uncommon.
It is mostly seen along with other vitamin
deficiency.
 Chronic alcoholics are susceptible to B2
deficiency.
 Assay of the enzymes glutathione reductase in
erythrocytes will be useful in assessing riboflavin
deficiency.
 Niacin (B3)
Structure

NicotinicAcid = Niacin
Nicotinamide =
Niacinamide
 Cofactor Forms
 Nicotinamide Adenine Dinucleotide
– NAD
– nicotinamide-ribose-PP-ribose-adenine
 Nicotinamide Adenine Dinucleotide
Phosphate
– NADP
– nicotinamide-ribose-PP-(ribose-P)-adenine
 Nicotinic Acid (Plant form)

Nicotinamide (animal form)

(reduced form)
 nicotinamide

adenine

If Phosphate here ->

Nicotinamide Adenine Dinucleotide NADP
Chemical Characteristics
 relatively stable to
– light
– heat
– oxidation
– alkali

 major losses due to leaching

 Digestion and Absorption

 Coenzyme form in food

 hydrolysis in small intestine to free
vitamin
 absorbed in duodenum

 nicotinic acid protein bound in corn

– requires alkali treatment (lime) to

release niacin
 Metabolism
 conversion of free vitamin to
coenzyme in all cells
 no storage

 excesses metabolized in liver

to variety of chemicals
 metabolites excreted in urine
 Synthesis
 from Tryptophan
 pathway requires B6 (also B2)

 60 mg of Tryptophan required to
make 1 mg B3
 corn is low in both B3 and
Tryptophan
 Biochemical
Functions
 Oxidation-Reduction
Reactions (NAD/NADH)
–Dehydrogenases
–Electron Transport System
–Involved in energy production
 Biochemical
Functions
 Synthetic Pathways
(NADPH)
–FA synthesis
–Cholesterol synthesis
–Non Essential AA synthesis
–Purine & Pyrimidine synthesis
 Recommended Dietary Allowance

 The daily requirement of niacin for an

adult is 15-20 mg and for children around
10-15 mg .
 Very often the term niacin equivalents
(NE) is used while expressing its RDA.
 One NE= 1 mg niacin or 60 mg of
tryptophan.
 Pregnancy and lactation women impose
an additional metabolic burden and
increase the niacin requirement.
 Dietary Sources
 The rich natural sources of niacin include liver,
yeast, whole grains, cereals, pulses like beans
and peanuts.
 Milk, fish, egg and vegetables are moderate
sources.
 The essential amino acid tryptophan can serve
as a precursor for the synthesis of nicotinamide
coenzymes.
 Tryptophan has many other essential and
important function in the body, hence dietary
tryptophan cannot totally replace niacin.
 Deficiency
 Pellagra (rough skin)
 Dermatitis (inflammation of skin)

 Dementia (degenaration of nervous

system)
– confused, disoriented
 Diarrhea
– irritation/inflammation of mucous membranes
 2000 RDA for Niacin
 NiacinEquivalents (NE)
 1 NE = 1 mg B-3 = 60 mg Try
Males Female
19-30 yrs 19-30 yrs
RDA (NE/d) 16 14
EAR (NE/d) 12 11
UL (NE/d) 35 35
NHANES III 25 20
Median intake
 Pyridoxine (B6)

 Vitamin B6 is used to collectively

represent the three compounds
namely pyridoxine, pyridoxal and
pyridoxamine (the vitamers of B6).
 Chemistry
 Vitamin B6 compounds are pyridine derivatives.
They differ from each other in the structure of a
functional group attached to 4th carbon in the
pyridine ring.
 Pyridoxine is a primary alcohol, pyridoxal is an
aldehyde form while pyridoxamine is an amine.
 Pyridoxamine is mostly present in plants while
pyridoxal and pyridoxamine are found in animal
foods.
 Pyridoxine can be converted to pyridoxal and
pyridoxamine, but the latter two cannot form
pyridoxine.
 Synthesis of Coenzyme

 The active form of vitamin B6 is the

coenzyme pyridoxal phosphate (PLP).
 PLP can be synthesized from the three
compounds pyridoxine, pyridoxal and
pyridoxamine.
 B6 is excreted in urine as 4-pyridoxic acid.
 Biochemical Functions

 Pyridoxal phosphate (PLP), the coenzyme

of vitamin B6 is found attached to the E-
amino group of lysine in the enzyme.
 PLP is closely associated with the
metabolism of amino acids.
 The synthesis of certain specialized
products such as serotonin, histamine,
niacin coenzymes from amino acids is
dependent on pyridoxine.
 Pyridoxal phosphate participates in
reactions like transamination,
decarboxylation, deamination,
transsulfuration, condensation.
 Pyridoxal phosphate is required for the
synthesis of δ- amino levulinic acids, the
precursor for the heme synthesis.
 The synthesis of niacin coenzymes from
tryptophan is dependent on PLP. The
enzyme kynureninase requires PLP.
 PLP plays important role in the
metabolism of sulphur containing amino
acids.
 The enzyme glycogen phosphorylase that
cleaves glycogen to glucose 1-phosphate
contains PLP, covalently bound to lysine
residue.
 Adequate intake of B6 is useful to prevent
hyperoxaluria and urinary stone formation.
 Recommended Dietary
Allowance
 The requirement of pyridoxine for an
adult is 2- 2.2mg/day.
 During lactation, pregnancy and old
age, an intake of 2.5mg/day is
recommended.
 Dietary Sources
 Animal sources such as egg yolk, fish,
milk, meat are rich in B6.

 Wheat, corn, cabbage, roots and

tubers are good vegetables sources.
 Deficiency Symptoms
 Pyridoxine deficiency is associated with
neurological symptoms such as depression,
irritability, nervousness and mental
confusion.

 Convulsions (epilepsy) and peripheral

neuropathy are observed in severe
deficiency. These symptoms are related to
the decreased synthesis of biogenic amines
(serotonin, GABA, norepinephrine and
epinephrine).
 In children B6 deficiency with
a drastically reduced GABA production
results in convulsions (epilepsy).

 Decrease in hemoglobin levels, associated

with hypochromic microcytic anemia, is
seen in B6 deficiency. This is due to a
reduction in heme production.
 Biotin

 Biotin (formally known as anti-egg

white injury factor, vitamin B7 or
vitamin H) is a sulfur containing B-
complex vitamin.

 It directly participates as a coenzyme

in the carboxylation reactions.
 Chemistry
 Biotin is a heterocyclic sulfur containing
monocarboxylic acid. The structure is
formed by fusion of imidazole and
thiophene rings with a valeric acid side
chain.
 Biotin is covalently bound to e-amino
group of lysine to form biocytin in the
enzymes.
 Biocytin may be regarded as the
coenzyme of biotin.
 Biochemical Functions

 Biotin serves as a carrier of CoA in carboxylation

reactions. The reaction catalyzed by pyruvate
carboxylase, converting pyruvate to
oxaloacetate has been investigated in detail.
 Recommended Dietary Allowance

 A daily intake of about 100-300 mg is

recommended for adults.
 In fact, biotin is normally synthesized by
the intestinal bacteria. However, to what
extent the synthesized biotin contributes to
the body requirements is not clearly
known.
 Dietary Sources

 Biotin is widely distributed in both

animal and plant foods.

 The rich sources are liver, kidney , egg

yolk, milk, tomatoes grain etc.
 Deficiency Symptoms

 The symptoms of biotin deficiency

include anemia, loss of appetite,
nausea, dermatitis, glossitis etc.
 Biotin deficiency may also result in
depression, hallucinations, muscle
pain and dermatitis.
 Pantothenic Acid

 Pantothenic acid (Greek: Pantos-

everywhere) formerly known as chick
anti – dermatitis factor (or filtrate
factor) is widely distributed in nature.
 Its metabolic role as coenzyme A is
also widespread.
 Chemistry and Synthesis of
Coenzyme A

Pantothenic acid consists of two

components , pantoic acid and β-
alanine, held together by a peptide
linkage.
 Synthesis of coenzyme A from
pantothenate occurs in a series of
reactions.
Biochemical Functions
 The function of pantothenic acid are
exerted through coenzyme A or CoA (A
for acetylation).
 Coenzyme A is a central molecule
involved in all the metabolism
(carbohydrate, lipid and protein).
 It play a unique role in integrating various
metabolism pathways.
 More than 70 enzymes that depend on
coenzyme A are known.

 Coenzyme A serves as a carrier of
activated acetyl or acyl groups (as thiol
esters).This is comparable with ATP which
is a carrier of activated phosphoryl groups.
 Coenzyme A may be regarded as a
coenzyme of metabolic integration since
acetyl CoA is a central molecule for a wide
variety of biochemical reactions.
 Succinyl CoA is also involved in many
reactions including the synthesis of
porphyrins of heme.
 Besides the various function through
coenzyme A, pantothenic acid itself is a
component of fatty acid synthase complex
and is involved in the formation of fatty
acid.
 Recommended Dietary Allowance
 The requirement of pantothenic acid for
humans is not clearly known. A daily
intake of about 5-10 mg is advised for
adults.
Dietary Sources
 Pantothenic acid is one of the most widely
distributed vitamins found in plant and
animals. The rich sources are egg, liver,
meat, yeast, milk etc.
 Deficiency Symptoms

 The burning feet syndrome pain and

numbness in the toes, sleeplessness,
fatigue etc.
 Pantothenic acid deficiency in
experimental animals results in anemia,
fatty, liver, decreased steroid synthesis
etc.
 Folic Acid / Folacin
 Structure
– pteridine ring - PABA - glutamate
 Stability

– very sensitive to heat

– easily oxidized
– leached
 Folic Acid

 Folic acids or folacin (Latin folium leaf)

is abundantly found in green leafy
vegetables.
 It is important for one carbon
metabolism and is required for the
synthesis of certain amino acid,
purines and the pyrimidine thymine.
Digestion and Absorption
 dietary form: polyglutamyl folate
– glutamate gamma linked
 Folate conjugase
– Zinc deficiency
– alcoholism
– drug interactions
 folate absorbed as monoglutamate
(free folate)
 dietary supplement: free folate
 Biochemical Functions

 Tetrahydrofolate (THF or FH4) the

coenzyme of folic acid is actively involved
in the one carbon metabolism.
 THF serves as an acceptor or donor of
one carbon units (formly, methyl etc).
 In a variety of reaction involving amino
acid and nucleotide metabolism.
 Many important compounds are
synthesized in one carbon metabolism.
1. Purines (carbon 2,8) which are incorporated
into DNA and RNA.
2. Pyrimidine nucleotide deoxythymidylic acid
(dTMP) involved in the synthesis of DNA.
3. Glycine, serine, ethanolamine and choline
are produced.
4. N-formylmethionine, the inititator of protein
biosynthesis is formed.
 Recommended Dietary Allowance

 The daily requirement of folic acid is

around 200 μg.

 In the women, higher intakes are

recommended during pregnancy (400 μg/
day) and lactation (300 μg/day).
 Dietary Sources

 Folic acid is widely distributed in

nature.
 The rich sources are green leafy
vegetables, whole grains, cereals,
liver, kidney, yeast and eggs.
 Milk is rather a poor source of folic
acid.
 Deficiency Symptoms
 Folic acid deficiency is probably the most
common vitamin deficiency, observed
primarily in the pregnant women, in both
developed (including USA) and developing
countries (including india).
 The pregnant women, lactating women,
women on oral contraceptives, and
alcoholics are also susceptible to folate
deficiency.
 The folic acid deficiency may be due to
(one or more causes) inadequate dietary
intake, defective use of anticonvulsant
drugs (phenobarbitone, dilantin ,
phenyltoin), and increased demand.
 The microcytic anemia (abnormally large
RBC) associated with megaloblastic
changes in bone marrow is a characteristic
feature of folate deficiency.
Folate Deficiency
 Megaloblastic Anemia
 decreased DNA synthesis
 failure of bone marrow cells to divide

 normal protein synthesis

 results in large immature RBC’s

 contrast with microcytic hypochromic

anemia
Folate and Neural Tube
Defects
 Defects in formation of neural
tube (brain & spinal cord)
 First two months gestation

 Anencephaly

– absenceof cerebral
hemispheres
Folate and Neural Tube
Defects
 Spina bifida
– defective closure of vertebral column
– spinal cord protrusion from spinal
column results in damage to spinal
cord
– lower limb and hip paralysis
– rectal and bladder problems
 NTD Prevalence
 US:

– 4000 live births with NTDs/yr

– 1/1000 pregnancies

 World:
– 400,000 live births with NTDs/yr
 NTDs and Folate
 NTDs associated with mothers with
low blood [folate]
 Estimated that 50% of NTDs
prevented with folate supplementation
200 ug/day
 DRI adults = 400 ug/day

 DRI prenancy = 600 ug/day

 typical US intake = 280-300 ug/day

 Folate and Grain
Enrichment
 Jan 1st, 1998
 140 ug/100g enriched grain

 results in additional 100 μg/day

 may reduce about 25% of NTDs

 limited because of masking of B-

12 deficiency
 Folate: 2000 DRI

 Dietary Folate Equivalents (DFE)

– 1 DFE =
1 ug food folate
 0.6 ug fortified food folate taken with food

 0.5 ug folate supplement on empty stomach

 Folate DRI (2000)
Males Females
19-30 yr 19-30 yr
RDA (ug/d) 400 400
EAR (ug/d) 320 320
UL (ug/d) 1000 1000
NHANES III 277 223
Median intake (prior
to fortification)

For women capable of becoming pregnant, it is

recommended that they consume 400 ug of folate as
supplements or fortified foods in addition to folate
containing foods.
 Vitamin B12
 Structure
 cobalamine

 methyl
cobalamine
– transport and
coenzyme form
 adenosyl
cobalamine
– storage and
coenzyme form
Dietary Sources
 Animal products
– including milk and eggs
 GImicroorganisms
 Vegan sources

– N-fixing legumes
– fortified grains
– vitamin supplements
Digestion and Absorption
 Protein bound in foods
 released by acid and pepsin
– Elderly at risk
 Intrinsic Factor
 gastric glycoprotein
 binds with B12 in small intestine
 IF-B12 complex binds to B12receptor in
ileum for absorption
 B12 absorption requires functioning
stomach, pancreas, and ileum
 Causes of B12
Deficiency
 Inadequate intake - rare
 DRIadults 2.4 ug/day
 Usual intake 7-30 ug/day

 Malabsorption of B12
 IF deficiency
 other GI tract problems
 Functions
 Homocysteine to Methionine
– methionine synthetase
 requires 5-methyl THF
 deficiency of B12 results in “methyl-
trap” of folate
– results in megaloblastic anemia
– synergistic effect of B12 and folate
 Deficiency
 Pernicious anemia
 megaloblastic anemia
– Methyl-folate trap
– Delayed or failure of normal cell division
due to impaired DNA synthesis
 neuropathy
– defective myelination
– progressive peripheral weakening
– unresponsive to folate
– upper limit to folate
supplementation/enrichment
 Vitamin C - Ascorbic
Acid
 Structure
 Metabolism
– oxidation/reduction
– dehydroascorbic acid
– dehydroascorbate
reductase
– glutathione (GSH)
 glutamate-cysteine-
glycine
 Functions
 Enhances absorption of
iron
 reduces iron to more
absorbable ferrous form
 chelates with ferrous ion to
make it more soluble
 Functions
 Involves O2 and metal coenzyme
– (ferrous, cuprous)
 Tyrosine synthesis & catabolism

 Synthesis of Neurotransmitters
– Dopamine
– Norepinephrine
– Serotonin
– Bile acid synthesis
 Functions
 Antioxidant Activity
 Reactsand removes active
oxygen species
 Pro-oxidant Activity
 Reduces metals to their pro-
oxidant forms
 Scurvy
 Bleeding gums
 easy bruising

 impaired wound healing and

bone repair
 joint pain

 anemia
 RDA
 10 mg/day prevents scurvy
 historic RDA’s 45-70 mg
(60mg in1989), 75mg in 2000
 prevention of scurvy vs
antioxidant effect with
supplements?
 Toxicity C
 UL adults: 2000mg/d
 Osmotic diarrhea

 Oxalate kidney stones

 Decreases uric acid reabsorption

resulting in increased risk of gout
 Affects diagnostic tests in feces and
gout
– fecal blood
– urinary glucose