VITAMIN - K

Dr. Aliya Jafri

Assistant Professor, Biochemistry,
SMC, JSMU.
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Learning objectives
VITAMIN K AND E
Chemical Forms. Sources. Daily
requirement, digestion & absorption.
Functions. Deficiency. Toxicity.
 CASES

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Vitamin K- Chemistry
A group of lipophilic and hydrophobic
vitamins.
Three compounds have the biological activity
of vitamin K
Phylloquinone (Vitamin K1), the normal
dietary source, found in green vegetables
Menaquinones (vitamin K2), synthesized
by intestinal bacteria.
Menadione synthetic compounds that can
be metabolized to phylloquinone.
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Vitamin K- Chemistry

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Vitamin K- Chemistry
Vitamin K family are naphthoquinone
derivatives .
Phylloquinone and menaquinones, both have
a long isoprenoid side chain.
The length of the side chain differs.
Phylloquinone have a 20 C side chain ,
whereas menaquinones have a 30 C side
chain.
The isoprenoid chain makes these vitamin
hydrophobic or lipophilic.
The synthetic vitamin K (menadione,
menadiol diacetate) have only hydrogen in
place of isoprenoid side chain that makes
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Dietary Sources
Vitamin K is found
in green leafy
vegetables such as
spinach, cabbage
and broccli.
Appreciable
amounts are also
present in egg yolk
and liver.
Vitamin K is present
in vegetable oils and
is particularly rich
in olive, canola, and
soybean oils.
Some amount is
contributed by
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Absorption, Transportation and Storage Impaired
Absorption takes Absorption
place in intestine in Fat malabsorption.
the presence of bile Vitamin K is
salts.
important for the
The transportation
from intestine is coagulation process.
carried out through In its deficiency
chylomicrons. resulting in tendency
Storage occurs in for bleeding and
liver and from liver
to peripheral cells is hemorrhages.
carried out bound Absorption decreased
with lipoproteins. by mineral oil, bile
Vitamin K3 is readily acid sequestrants
absorbed without
requiring bile salts (Cholestyramine,
Colestipol) and
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Orlistat (weight loss 8
Recommended daily
allowance
The adequate intake for vitamin K is
120 mg/day for adult males and 90 mg
for adult females.
The average daily allowance is 50-100
mg/day.
Requirement increases in –
Liver disorders
Patients on prolonged antibiotic
therapy, bile acid sequestrants
(Cholestyramine, colestipol) and
Orlistat (weight loss medication)
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Role in
blood
coagulatio Role in bone
n mineralization
•Cofactor for gamma
• Cofactor for gamma carboxylation of
carboxylation of glutamic acid in
glutamic acid in osteocalcin
clotting factors
II, VIII, IX and X
FUNCTIONS OF VITAMIN K
Blood Coagulation
 The main function of vitamin K the promotion of
blood coagulation by helping in the
posttranscriptional modifications of blood factors
such as prothombin and factors II, VII, IX, X.
 Vitamin K is first converted to its hydroquinone form
in liver microsomes by dehydrogenase using NADPH.
It then functions as coenzyme for carboxylase. It uses
CO2 to be incorporated as an additional –COOH group
at the γ- C of a specific glutamate of these
coagulation proteins.
 This converts the glutamate residues into γ-
carboxyglutamate.
 Hydroquinone may change to 2, 3 epoxide which is
reduced back to quinone by microsomal epoxide
reductase.
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Vitamin K cycle

Reduced lipoamide is required for the activity of

Epoxide reductase whereas NADPH is needed
for the action of vitamin K reductase.
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Functions of vitamin K
Calcium Binding Proteins

Vitamin K is found to carboxylate specific

glutamate residues of calcium binding
proteins of bones, spleen, placenta and
kidneys.

 This enhances the capacity of these proteins

to deposit calcium in the tissues concerned.

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Role in Oxidative
Phosphorylation
Vitamin K is a necessary cofactor in
oxidative
phosphorylation of mitochondrial lipids.

UV irradiation of isolated mitochondria

destroys their
vitamin K content and ultimately their
ability for oxidative phosphorylation. The
normal process of oxidative phosphorylation
is restored when vitamin K is added to them.

 Dicumarol, an antagonist of vitamin

K, is known to act as uncoupler of
oxidative phosphorylation.
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Vitamin K Antagonists
Dicumarol and Warfarin, inhibit
coagulation through antagonist action of
vitamin K.
Warfarin prevents the recycling of
vitamin K by inhibiting two important
reactions and creating a functional
vitamin K deficiency
Warfarin is a competitive inhibitor of
Epoxide reductase.
In the presence of Warfarin, vitamin K
epoxides cannot be reduced, they
accumulate and are excreted.
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Vitamin K deficiency
Causes
Lack of vitamin K in the diet

Fat malabsorption that reduce the

absorption of vitamin K
Disease or surgical interventions that

affect the ability of the intestinal tract to

absorb vitamin K
Chronic liver diseases
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Vitamin K deficiency in
the newborn
• Maternal medications that interfere with vitamin

K stores or function (e.g., carbamazepine,

phenytoin, barbiturates, some Cephalosporins,
rifampin, Isoniazid, Warfarin or Warfarin like
drugs) can result in vitamin K deficiency bleeding
in the infant.
•Transplacental transfer of vitamin K is very

limited during pregnancy,

•The storage of vitamin K in neonatal liver is also

limited.
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Clinical Manifestations
The main symptom is bleeding
(hemorrhage)—into the skin (causing
bruises), from the nose, from a wound, in
the stomach, or in the intestine.
Blood may be seen in the urine or stool.
In newborns, life-threatening bleeding within
or around the brain may occur.
Having a liver disorder increases the risk of
bleeding because proteins that help blood
clot (clotting factors) are made in the liver.
Vitamin K deficiency may also weaken bones. 19
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Clinical Manifestations
A deficiency
of vitamin K
can lead to
extreme
bleeding,
which can
begin as a
gum or nose
discharge or
bruising

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Treatment
A vitamin K injection
in the muscle is
recommended for all
newborns to reduce
the risk of bleeding
within the brain
after delivery.
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Treatment
For patients with

chronic
malabsorption, 1–2
mg/d of vitamin K
should be given
orally, or 1–2
mg/week can be
taken parenterally.
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Prevention
Intramuscular (IM) vitamin K
prophylaxis at birth is the standard of
care.

Commercial infant formulas contain

supplemental vitamin K.

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 Summary
Vitamin K is a fat soluble vitamin
Phylloquinone, Menaquinone and
Menadione are the members of vitamin K
family
Vitamin K acts as a coenzyme for the
gamma carboxylation of glutamic
residues of Calcium binding proteins
Plays an important role in blood clotting,
bone formation and prevention of
calcification of soft tissues
Deficiency of vitamin K is manifested in
the form of bleeding tendencies and
hemorrhages
Oral or injectable vitamin K can be
recommended depending upon the
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 VITAMIN - E


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VITAMIN E CHEMISTRY

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 Distribution and requirements of
vitamin E
Vegetable oils are
rich sources of
vitamin E, whereas
liver and eggs
contain moderate
amounts.
The RDA for α-
tocopherol is 8 - 10
mg/day for adults.
The vitamin E
requirement
increases as the intake
of polyunsaturated FA
increases to limit FA
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 8 – 10
RD
mg/
A day

The daily requirement increases with

increase in dietary intake
of PUFA
Absorpti
on Transp Stora
ort ge
Upper Chylomicr Adipose
intestin on tissue
e
Along VLDL
with and live
lipids LDL r
 Biochemistry for medics- Lecture Notes-
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 Prevents lipid
As a biological peroxidation of
antioxidant biological
membrane
Vitamin
E

Prevents Reproductive
peroxidation of functions &
vitamin A & prevents sterility
PUFA
 The main function of Vitamin E (alpha-tocopherol)
is that of an antioxidant. An antioxidant is a
substance that reduces or prevents damage.
Free radicals are very
reactive atoms or
molecules that typically
possess a single unpaired
electron. They are
formed in the body
during normal
metabolism and also
upon exposure to
environmental factors
such as cigarette smoke, Fats and some proteins are the
stress, alcohol, lack of
target of free radical destruction.
sleep, poor diet, or
pollutants. These free The result is damage to the cell
radicals cause membranes and accelerated aging.
destruction by trying to It is also linked to Alzheimer’s
remove electrons from disease, cataracts, heart disease,
other molecules so they Vitamin K usage, and cancer.
 FUNCTIONS

Biochemistry for medics- Lecture Notes-

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 Vitamin E
Powerful Antioxidant
Protects cell membranes; prevents oxidation
of LDL cholesterol
 α-Tocopherol
α-Tocopherol is an important lipid-
soluble antioxidant.
It performs its functions as antioxidant
by the glutathione peroxidase
pathway and it protects cell
membranes from oxidation by reacting
with lipid radicals produced in the lipid
peroxidation chain reaction.
This would remove the free
radical intermediates and prevent
the oxidation reaction from continuing.
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 VITAMIN –
• Membrane
antioxidant
E

• Vit - E supplemention for CVD patients

• Cambridge Heart Antioxidant study - dec.
mortality due to M.I
Tocotrienols – inhibit platelet aggregation – thrombus
formation
hv cholesterol lowering effect
• Prevents peroxidation of PUFA
 Selenium
complements the
antioxidant effects of
vitamin E and
reduces the
requirement of
vitamin E
 Deficiency of vitamin E
Newborns have low reserves of vitamin E,
but breast milk (and formulas) contain the
vitamin.
Very-low-birth-weight infants may be given
supplements to prevent the hemolysis and
retinopathy associated with deficiency of
vitamin E.
When observed in adults, deficiency is
usually associated with defective lipid
absorption or transport.
[Note: Abetalipoproteinemia, caused by a
defect in the formation of chylomicrons and
VLDL, results in vitamin E deficiency
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 Vitamin E
Deficiency vs Toxicity

Deficiency Adequacy Toxicity

(<66% of DRI) DRI: 15 mg/day (>UL)
Approx. <10 mg/day RDI: 30 IU >1,000 mg/day

Premature Normal cell Relatively nontoxic

infants: membrane Toxicity with
hemolytic integrity, reduced supplements
anemia oxidative stress, Interferes with
Adults: not well and molecular vitamin K’s role in
characterized functioning blood clotting,
augmentation of
anti-blood clotting
medication and
increases hemolysis
Toxicity of vitamin E

Vitamin E is the least toxic of the fat-

soluble vitamins
 no toxicity has been observed at doses of
300 mg/day (UL = 1,000 mg/day).

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 Reference
LIPINNCOTT’S BIOCHEMISTRY

CHATERJEE’S BIOCHEMISTRY

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 THANK YOU

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