Water solible vitamines

Water soluble vitamins

Prof.Dr.Esam Abd El Mohsen Afifi

 Overview
• Vitamins are chemically unrelated organic compounds that cannot be
synthesized in adequate quantities by humans and, therefore, must
be supplied by the diet.
• Many of the water-soluble vitamins are coenzymes for the enzymes
of intermediary metabolism. But in fat soluble vitamin only one
(vitamin K) has a coenzyme function.
• Fat soluble vitamins are released, absorbed, and transported with
the fat of the diet. They are not readily excreted in the urine, and
significant quantities are stored in the liver and adipose tissue.
• Consumption of vitamins A and D in excess of the recommended
dietary allowances can lead to accumulation of toxic quantities of
these compounds.
 Folic Acid
• Function of Folic acid: Tetrahydrofolate receives
one-carbon fragments from donors (serine, glycine,
and histidine) and transfers them to intermediates in
the synthesis of amino acids, purines, and thymidine
monophosphate (TMP) a pyrimidine found in DNA.
THF as a carrier for one carbon fragment
Function of Folic acid
 Nutritional anemias

Anemia is a condition in
which the blood has a lower
than normal concentration
of hemoglobin, which results
in a reduced ability to
transport oxygen. Nutritional
anemias are those caused by
inadequate intake of one or
more essential nutrients

Classification of nutritional anemias by cell size

 Macrocytic (megaloblastic) anemias

These macrocytic anemias are

commonly called megaloblastic
because a deficiency of folic acid
or vitamin B12 causes accumulation
of large, immature red cell
precursors, known as
megaloblasts, in the bone marrow
and the blood.

Bone marrow histology in normal and folate-deficient individuals

Increased number of immature red cell precursors
History

The nutritional benefits of folic acid

were first observed by researcher
Lucy Wills in 1931 while she was
researching anaemia in pregnant
textile workers in Bombay, India. It
was here that she discovered that
treating these patients with yeast
and liver extracts cured the
anaemia
 Causes of folic acid deficiency
(1) Increased demand (pregnancy and lactation)

(2) Poor absorption caused by pathology of the

small intestine, alcoholism.

(3) Treatment with drugs that are dihydrofolate

reductase inhibitors (methotrexate ,
sulfonamides)

(4) A folate-free diet can cause a deficiency within a

few weeks. Green leafy vegetables (foliage) are
rich sources of folate and provide the basis for its
name.
 Results of folic acid deficiency
• Folic acid deficiency is the most common vitamin deficiency in
the USA , particularly among pregnant women and alcoholics.

• A primary result of folic acid deficiency is megaloblastic

anemia ,caused by diminished synthesis of purines and TMP,
which leads to an inability of cells to make DNA and, therefore,
they cannot divide. (It is important to evaluate the cause of the
megaloblastic anemia prior to instituting therapy, because
vitamin B12 deficiency indirectly causes symptoms of this
disorder)

• folic acid deficiency in the first trimester of pregnancy leads to

Spina bifida and anencephaly to the fetus.
Prevention of birth defects with folic acid

During the first trimester of pregnancy all

organs develop so the fetus is most susceptible
to damage from toxins, drugs, and infections.

Studies show that an increase in the mother's dietary folic acid

before conception and during the first month of pregnancy reduces
the risk of having a child with a neural tube defect.
 Folate and neural tube defects in the fetus
Spina bifida and
anencephaly, the most
common neural tube
defects, affect
approximately 4,000
pregnancies in the USA
annually. Folic acid
supplementation
before conception and
Spina Bifida is a condition during the first
wherein the spine of the baby
is left open owing to some
trimester has been
Anencephaly is a condition that
problem in the embryonic prevents proper development
shown to significantly
stage caused the neural tube of the fetus’ brain and which reduce the defects.
to remain open. results in death soon after birth
or even a still birth.
 Folic Acid Fortification
• all women of childbearing age are advised to consume 0.4
mg/day of folic acid to avoid neural tube defects.
• Adequate folate nutrition must occur at the time of conception
because critical folate-dependent development occurs in the first
weeks of fetal life—at a time when many women are not yet
aware of their pregnancy.
• The U.S. FDA has authorized the addition
of folic acid to enriched grain products,
This supplementation will allow 50% of
all reproductive-aged women to receive
0.4 mg of folate from all sources.
• However, folic acid intake should not
exceed 1 mg/day to avoid complicating the diagnosis of vitamin
B12 deficiency.
Cobalamin (Vitamin B12)
Vitamin B12 is required for two
essential enzymatic reactions:

(1)the remethylation of homocysteine

to methionine

(2)the isomerization of
methylmalonyl CoA that is produced
during the degradation odd numbers
fatty acids. When the vitamin is
deficient, abnormal fatty acids
accumulate and become
incorporated into cell membranes,
including those of the nervous
system.
Structure of cobalamin and its coenzymes
 Folate trap

N10 formyl THF

DNA synthesis

Cobalamin deficiency is most pronounced in rapidly dividing cells ( as

erythropoietic T. ) . Such tissue need both the N5-N10-methylene & N10
formyl THF for the synthesis of nucleotides for DNA replication.
In vitamin B12 deficiency, the utilization of the N5-methyl THF cannot be
converted directly to other forms of THF , so folate is trapped in the N5-
methyl form, which accumulates while other forms of folate decrease.
Thus, cobalamin deficiency lead to a deficiency of the THF forms needed
in DNA synthesis, resulting in the symptoms of megaloblastic anemia.
Megaloblastic anaemia
• The RBC are very large, the
inner contents of each cell are
not fully developed. They
have higher nuclear-to-
cytoplasmic ratios , The bone
marrow to produce fewer
cells, & sometimes the cells
die earlier than the normal
120-day life expectancy.
• Neutrophils can be
hypersegmented
 Causes of Vitamin B12 deficiency
(1) Vitamin B12 deficiency is rarely a result of an absence of the
vitamin in the diet.

(2) The disease is most commonly a result of an autoimmune

destruction of the gastric parietal cells that are responsible
for the synthesis of intrinsic factor . The disease was called
pernicious anemia, because it was fatal before treatment
was available for the first time as a therapy for liver and
later as a purified vitamin B-12. The term pernicious is no
longer appropriate, but is kept for historical reasons.

(3) in individuals who had a partial or total gasterectomy .

 Distribution of cobalamin

• Vitamin B12 is synthesized only by

microorganisms; it is not present
in plants (Vegeterians are at risk).
• Animals obtain the vitamin
preformed from their natural
bacterial flora or by eating foods
derived from other animals.
Cobalamin is present in
appreciable amounts in liver,
whole milk, eggs, oysters, fresh
shrimp, pork, and chicken
Absorption of vitamin B12
Normally, vitamin B12 obtained from
the diet binds to intrinsic factor in
the intestine .The cobalamin–
intrinsic factor complex travels
through the gut and eventually binds
to specific receptors on the surface
of mucosal cells of the ileum. The
bound cobalamin is transported into
the mucosal cell and, subsequently,
into the general circulation, where it
is carried by B12-binding proteins.
Lack of intrinsic factor prevents the
absorption of vitamin B12, resulting in
pernicious anemia.
Function of Vitamin B12
1. Vitamin B12 is known as the
“energy vitamin” because it
supports energy pathways so is
used to remedy fatigue.
2.  It is also part of the healthy
formation of red blood cells that
carry oxygen to body tissues.
3. It is also used to reduce serum
homocysteine levels (which
when elevated indicates an
increased risk of cardiovascular
disease)
4. It is also involved in nerve health
and DNA repair.
 Symptoms of Vitamin B-12
deficiency
• Symptoms are nonspecific including:
* Fatigue (temporary loss of strength)
* Lassitude (listlessness)
* Malaise (a vague sense of illness)
* Vertigo
* Cognitive impairment

• However, you definitely have Vitamin B

deficiency if you have the following symptoms:
* macrocytic anemia
* peripheral neuropathy
* subacute combined degeneration of spinal
cord
Ascorbic Acid (Vitamin C)
 Functions of ascorbate
(1) A reducing agent in several different reactions.
(2) a coenzyme in hydroxylation reactions,
e.g.hydroxylation of prolyl and lysyl residues of
collagen , so vitamin C is required for the
maintenance of normal connective tissue and
wound healing.
 (3) facilitates the absorption of dietary iron from
the intestine. Iron is an important building
block of RBC, so vitamin C is important to
produce healthy blood cells.

Ferrireductase (reduces Fe+++ to Fe++ )

divalent metal transporter DMT-1
Deficiency of ascorbic acid
A deficiency of
ascorbic acid results
in scurvy, a disease
characterized by
sore and spongy
gums, loose teeth,
fragile blood vessels,
swollen joints, and
anemia.Many of the
deficiency symptoms
can be explained by
a deficiency in the
hydroxylation of
collagen, resulting in
defective connective
Vit C and Common Cold
Despite the popular belief that vitamin
C can cure the common cold, scientific
evidence doesn't support the notion.
Taking vitamin C supplements regularly
(not just at the beginning of a cold)
produces only a small reduction in the
duration of a cold (about 1 day).
Pyridoxine (Vitamin B6)
Vitamin B6 is a
collective term for
pyridoxine,
pyridoxal, and
pyridoxamine,
all derivatives of
pyridine. They differ
only in the nature of
the functional group
attached to the ring .
Vitamin B6
• Pyridoxine occurs primarily in
plants, whereas pyridoxal and
pyridoxamine are found in animal
foods.

• All three compounds can serve

as precursors of the biologically
active coenzyme, pyridoxal
phosphate.

•
 Reactions of PLP
PP functions as a coenzyme for a large number of enzymes that
catalyze reactions involving amino acids.

It is essential for protein metabolism, and formation of haemoglobin

Transamination

Aspartate transaminase
Deamination
Decarboxylation
Condensation

This reaction is catalyzed by δ-aminolevulinate

synthase, a PLP enzyme present in
mitochondria
Clinical indications for
pyridoxine
 Isoniazid (isonicotinic acid hydrazide), a drug
frequently used to treat tuberculosis, can induce a
vitamin B6 deficiency by forming an inactive
derivative with pyridoxal phosphate. Dietary
supplementation with B6 is, thus, an adjunct to
isoniazid treatment.
 Otherwise, dietary deficiencies in pyridoxine are rare
but have been observed in :
-newborn infants fed formulas low in B6,
- women taking oral contraceptives,
-in alcoholics.
 Clinical indications for pyridoxine
• Isoniazid treatment can induce a
vitamin B6 deficiency by forming an
inactive derivative with pyridoxal
phosphate. Dietary supplementation
with B6 is, an adjunct to isoniazid
treatment.

• dietary deficiencies are rare but have

been observed in :
a -newborn infants fed formulas low in
B6, Isoniazid
b - women taking oral contraceptives, (isonicotinic acid hydrazide)
to treat tuberculosis
c -in alcoholics.
Toxicity of pyridoxine
- Neurologic symptoms have been observed at
intakes of greater than 2 g/day(Headache
,Fatigue ,Numbness , Walking problems , Poor
coordination ,Loss of sensation to touch).

Bananas are a good source of vitamin B6

 Thiamine (Vitamin B1)

(TPP), is a cofactor involved in the citric acid cycle, as well as connecting the breakdown of
sugars with the citric acid cycle. The disruption of citric acid cycle due to thiamine deficiency
inhibits the production of many molecules including the neurotransmitters glutamic acid and
GABA.
Reactions that use
TPP as coenzyme
A. Transketolase.
B. Pyruvate dehydrogenase
and α-ketoglutarate
dehydrogenase.
A ) TPP as a coenzyme for
Transketolase
 b) TPP as a coenzyme for PDH
In thiamine deficiency, the activity of PDH and alpha ketoglutarate
dehydrogenase decreased, resulting in a decreased production of ATP .
Functions of vit B1
 Beriberi "I can't, I can't"
This is a thiamine-deficiency syndrome
found in areas where polished rice is the
major component of the diet.
• Infantile beriberi (acute beriberi) is
found mostly in babies include loss of
appetite, vomiting, lactic acidosis and
enlargement of the heart and, if not
treated, death.
• Adult beriberi ( chronic form ) devided
into wet beriberi, and dry beriberi is . In the early 1900s scientists
discovered that rice bran
characterized by dry skin, irritability, (that was removed to create
disorderly thinking, and progressive the polished white rice
preferred by Asians ) actually
paralysis. contained thiamine.
Dry beriberi Wet beriberi
Dry beriberi affects the nervous Wet beriberi affects the
system resulting in numbness of cardiovascular system resulting in
the hands and feet, confusion, a fast heart rate, shortness of
trouble moving the legs, and pain breath, and leg swelling
 Wernicke-Korsakoff syndrome
 Wernicke-Korsakoff syndrome is a
thiamine deficiency state in some
alcoholics characterized by apathy,
loss of memory, and nystagmus
(rhythmical to-and-fro motion of the
eyeballs).
 The neurologic consequences of
Wernicke's syndrome are treatable
with thiamine supplementation.
Intravenous thiamine administration
typically is initiated at 50 mg/day until
the same dose is tolerated orally.
Dry
beriberi

Wet
beriberi
 Niacin (nicotinic acid)
(Vitamin B3)

• The biologically active coenzymes of niacin are (NAD+) and (NADP+).

• Nicotinamide is readily deaminated in the body and, therefore, is
nutritionally equivalent to nicotinic acid
 Niacin (nicotinic acid)
(Vitamin B3)
 Niacin, is a pyridine derivative. The
biologically active coenzyme forms are
(NAD+) and (NADP+).

 Nicotinamide, a derivative of nicotinic acid

that contains an amide instead of a
carboxyl group, also occurs in the diet.
 Nicotinamide is readily deaminated in the
body and, therefore, is nutritionally
equivalent to nicotinic acid
 Biosynthesis of NAD+ and
NADP+.

Structure and biosynthesis of NAD+ and NADP+.

Note that tryptophan can also give NAD+.
Reduction of NAD+ to NADH
NAD+ and NADP+ serve as
coenzymes in oxidation-
reduction reactions in which the
coenzyme undergoes reduction
of the pyridine ring by accepting
a hydride ion (hydrogen atom
plus one electron).
 Distribution of niacin

 Niacin is found in unrefined and enriched

grains and cereal, milk, and lean meats,
especially liver.
 Deficiency of niacin causes
pellagra, a disease pellagra
involving skin, GIT, CNS.
The symptoms of pellagra
are three Ds: dermatitis,
diarrhea, dementia—and,
if untreated, death.

Degradation of spinal diarroeic stool

cord
 Pellagra

diarroeic
stool

Degradation of spinal cord

 Niacin decreases
hyperlipoproteinemia
Treatment of hyperlipidemia: Niacin (at doses
of 1.5 g/day or 100 times the RDA) strongly
inhibits lipolysis in adipose tissue—the primary
producer of circulating free fatty acids. The liver
normally uses these circulating fatty acids as a
major precursor for triacylglycerol synthesis.
Thus, niacin causes a decrease in liver
triacylglycerol synthesis, which is required for
VLDL and LDL production. Thus, both plasma
triacylglycerol (in VLDL) and cholesterol (in
VLDL and LDL) are lowered. Therefore, niacin
is particularly useful in the treatment of Type IIb
hyperlipoproteinemia, in which both VLDL and
LDL are elevated.
 Riboflavin (Vitamin B2)

The two biologically active forms are flavin mononucleotide (FMN) and flavin
adenine dinucleotide (FAD), formed by the transfer of an adenosine
monophosphate moiety from ATP to FMN
FMN and FAD
 Mechanism of action in redox reactions

It is yellow in color and the word "flavin" is derived from the latin word for yellow, flavus.
Flavin coenzymes can exist in three different redox states, and each state has a
different color.
 flavoenzymes
 FMN and FAD are each
capable of reversibly accepting
two hydrogen atoms, forming
FMNH2 or FADH2. FMN and
FAD are bound tightly—
sometimes covalently—to
flavoenzymes that catalyze the
oxidation or reduction of a
substrate.

The structure of succinate dehydrogenase

in a phospholipid membrane. SdhA(FAD
containing subunit), SdhB, SdhC and Sdh
 Riboflavin deficiency
Deficiency symptoms include :
• Dermatitis.
• cheilosis (fissuring at the corners
of the mouth), and
• glossitis (the tongue appearing
smooth and purplish).
 Biotin
Biotin is a coenzyme in carboxylation reactions so it
serves as a carrier of activated carbon dioxide . Biotin is
covalently bound to the ε-amino groups of lysine residues
of biotin-dependent enzymes
 Mechanism of action

acetyl-CoA carboxylase enzyme, the biotin ring, on its flexible tether, acquires carboxyl
groups from carbonylphosphate on the carboxylase subunit and transfers them to
acetyl-CoA molecules on the transcarboxylase subunits to form malonyl coA.(F.A.
synthesis)
 Biotin sources
 Biotin deficiency does not occur naturally
because the vitamin is widely distributed in
food and is supplied by intestinal bacteria.
Biotin deficiency
(egg white injury)
However, the addition of raw egg white to the
diet induces biotin deficiency. Raw egg white
contains a glycoprotein, avidin, which tightly
binds biotin and prevents its absorption from Raw egg whites can
neutralize biotin,
the intestine. However, it has been estimated so always cook your eggs

that 20 eggs/day would be required to induce

a deficiency syndrome. Thus, inclusion of an
occasional raw egg in the diet does not lead
to biotin deficiency.
However, eating raw eggs is generally not
recommended due to the possibility of
salmonella infection.
 Biotin
deficiency

symptoms of biotin deficiency

are dermatitis, glossitis, loss of
appetite, and nausea. In severe
cases, there may be hair, eye
lashes and eyebrows loss.  But,
there are no published
scientific evidence to support
high-doses of biotin
supplements  prevent or treat
hair loss in men or women.
 Pantothenic Acid
• Pantothenic acid is a component of CoA . Coenzyme A
contains a thiol group that carries acyl compounds
 Sources of Pantothenic Acid
• The term pantothenic acid
is derived from the Greek
word pantothen which
means “from every side ”
denoting widespread
availability in foods.
• Eggs, liver, and yeast are the
most important sources of
pantothenic acid.
• Pantothenic acid deficiency
is not well characterized in
humans.
• Which of the following is the most essential
nutrient for a woman during her initial stages of
pregnancy to prevent birth defects?
(a) Thiamin (b) Folic acid
(c) Vitamin C (d) Vitamin E

Which of the following is a component of the

coenzyme A?
(a) Retinol (b) Pyridoxine
(c) Retinoic acid (d) Pantothenic acid
• Which of the following statements is false about
Ascorbic acid?
(a) It shows antioxidant activity
(b) It is a strong reducing agent
(c) It can be synthesized in the body
(d) Involved in the hydroxylation of prolyl- and lysyl-
residues of collagen

Weakness in muscles and increase in the fragility of

red blood cells is caused due to the __________.
(a) Deficiency of vitamin E *
(b) Deficiency of vitamin D
(c) Deficiency of vitamin C
(d) Deficiency of vitamin A
• Q1 Two days after admission, a 57-year-old man suddenly has a seizure.He was
undergoing evaluation for substernal chest pain. The nursing staff noted that he
seemed to be a little shaky since shortly after arrival on the floor. He has no history
of seizures and a stat CT of the head performed was normal.
• Laboratory results had shown an
MCV of 101 (elevated) and
his AST was mildly elevated (one and one-half normal).
In this patient, the most likely imbalance that would contribute to
this event would be
a. Folate deficiency
b. Fasting hypoglycemia
c. Hypomagnesemia
d. Thiamine deficiency
e. Vitamin B12 deficiency

Seizures in this patient can be due to hypomangnesemiaBut since magnesium values are not given in the
vignette so it is normal
increased MCV --> B12 def --> Seizure....
folate is not associated with neurologiv signs
So correct answer is e
• Match the following:
• Name of Vitamin Chemical name
A. Vitamin B1 1. Cyanocobalamin
B. Vitamin B2 2. Pyridoxine
C. Vitamin B6 3. Thiamine
D. Vitamin B12 4. Riboflavin

40. The richest source of Vitamin A is _______.

(a) Orange (b) Apple (c) Eggs* (d) Meat

46. The diet should be rich in which of the following to

overcome the deficiency in vitamin D?
(a) Eggs and dairy products (b) Fresh vegetables
(c) Whole grain cereals (d) Citrus fruits
• 49. Certain bacteria living in the human digestive
system are beneficial because they synthesise vitamin
• (a) D (b) B-Complex
• (c) K (d) A

• Milk, cheese and eggs are the source of __________.

(a) Vitamin C and A (b) Vitamin A and D
• (c) Vitamin C and D (d) Vitamin B and C

• Vitamins act as_______.

(a) Ribonucleic Acid (b) Enzyme
(c) Co-enzyme (d) Amino Acid
• Functions: collagen synthesis ,antioxidant, restores vitamin E
to active form, supports immune cell functions, helps in
absorption of iron.
A. Vitamin A B. Thiamin (B1)
C. Riboflavin (B2) D. Vitamin C

Citrus fruits, cabbage type veggies, dark green veggies,

cantaloupe, strawberries, peppers, lettuce, tomatoes,
potatoes, papayas and mangoes are good sources of:
A. Thiamin (B1) B. Vitamin B12
C. Vitamin C D. Riboflavin (B2)
Functions: part of a co-enzyme needed for new cell synthesis.
A. Folate B. Pantothenic Acid
C. Vitamin B6 D. Vitamin B12
Toxicity of what vitamin causes: masking of Vitamin B12
deficiency.
A. Vitamin D B. Vitamin C
C. Pantothenic Acid D. Folate

Functions: part of co-enzyme needed in new cell syntheses

and helps maintain nerve cells.
A. Biotin B. Vitamin B12
C. Vitamin B6 D. Vitamin C

Egg is rich source of nutrients except

(a) Fats
(b) Vitamin A
(c) Protein
(d) Vitamin C
• Milk, cheese and eggs are the source of ___
• (a) Vitamin C and A (b) Vitamin A and D
• (c) Vitamin C and D (d) Vitamin B and C

• Which of the following is NOT a function of vitamins?

a)Helping in the absorption of calcium for healthy bones.
b) Protecting your cells from free radicals.
c) Aiding in blood clotting.
d) Providing energy in the form of glucose

Edgar hates carrots, but his mother told him he should eat his carrots
because they contain _____ which is good for his _____.
a) vitamin B, heart
b) vitamin A, eyes
c) vitamin C, skin
d) vitamin D, teeth
A. True B. False
*Excess fat soluble vitamins intake has a high
potential for toxicity
*Vitamins can supply energy and contribute to
body mass
*Vitamin C, A, D, E, K and chloine are all water
soluble vitamins
*Fat soluble vitamins can be taken in excess
without medical supervision