Download MBBS Vitamin K Lecture PPT

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"Koagulation "

? Anti-hemorrhagic factor
? Specific coenzyme function required for coagulation
? VITAMIN K are Naphthoquinone derivatives and

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have long side Isoprenoid chain.

? 1929 ? Henrick Dam ? isolation of Vitamin K1 ?(Noble

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Prize )

? 1939 ? Edward Doisy ? isolation of Vitamin K2 ?(Noble

Prize 1943 )

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Vitamin K- Chemistry

? Vitamin K represents a group of lipophilic and

hydrophobic vitamins.

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? Three compounds have the biological activity of

vitamin K

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? Phylloquinone (Vitamin K1), the normal dietary

source, found in green vegetables

? Menaquinones (vitamin K2), synthesized by

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intestinal bacteria, with differing lengths of side
chain; and

? Menadione and menadiol diacetate, synthetic

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compounds that can be metabolized to phylloquinone


Vitamin K are naphthoquinone

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derivatives


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.
ABSORPTION

? Absorption takes place in intestine in the

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presence of bile salts.

? The transportation from intestine is carried out

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through chylomicrons.

? Storage occurs in liver
? Transportation from liver to peripheral cells is

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carried out bound with beta lipoproteins.
Biochemical Functions of vitamin K

? Vitamin K act as a coenzyme for the

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carboxylation of glutamic acid residues present in
the protein and this reaction is catalyzed by a
carboxylase (microsomal)

? Although

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vitamin

K-dependent

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gamma-

carboxylation occurs only on specific glutamic
acid residues in a small number of vitamin K-
dependent proteins, it is critical to the calcium-

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binding function of those proteins
.

? It involves the conversion of glutamate (Glu)

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to -carboxyglutamate (Gla) and requires
vitamin K,O2 and CO2

? The formation of - carboxyglutamate is

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inhibited by dicumarol, an anticoagulant found
in spoilt sweet clover

? Warfarin is a synthetic analogue that can

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inhibit vitamin K action


.

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(Glu)

(Gla)
Vitamin K cycle

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? Vitamin K is a fat-soluble vitamin, the body

stores very little of it, and its stores are rapidly

depleted without regular dietary intake.

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? Because of its limited ability to store vitamin

K, the body recycles it through a process called

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the vitamin K cycle.

? The vitamin K cycle allows a small amount of

vitamin K to function in the gamma-

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carboxylation of proteins many times,

decreasing the dietary requirement.

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Quinone

DICUMAROL
.

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? Vitamin K hydroquinone (active form) is oxidized

to the Epoxide form during the process of
enzymatic reaction.

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? The initial form (hydroquinone form) is

regenerated by two steps process.

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? Vitamin K Epoxide is reduced to the quinone by a

Epoxide reductase, and

? the quinone is reduced to the active hydroquinone

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by

--either the same reductase or
---by a vitamin K reductase(quinone reductase).

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...Role In Clotting

? The functions of vitamin K are concerned with

blood clotting process.

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? The clotting factors II, VII, IX and X are

synthesized as inactive precursors in the liver.

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? Vitamin K brings about post-translational

modification i.e. carboxylation of glutamic
acid residues of these blood clotting factors.
.

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? - Carboxyglutamic acid (Gla) residues of

clotting factors are negatively charged (COO-)
and they combine with positively charged

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calcium ions (Ca2+) to form a complex

? The complex binds to the phospholipids on the

membrane surface of the platelets.

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? Leads to increased conversion of prothrombin

to thrombin
OTHER FUNCTIONS

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? Vitamin K is also important in synthesis of two

proteins that contain -carboxyglutamate that
are present in bone-

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1. Osteocalcin and
2. Bone matrix Gla protein.
1. Osteocalcin is a protein synthesized by

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osteoblasts.

? The synthesis of osteocalcin by osteoblasts is

regulated by the active form of vitamin D,

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1,25(OH)2D3 or calcitriol. .
? The mineral-binding .capacity of osteocalcin

requires

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vitamin

K-dependent

gamma-

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carboxylation of three glutamic acid residues

? After gamma carboxylation osteocalcein binds

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tightly to calcium.

? Osteocalcin also contains hydroxy proline, so

its synthesis is dependent on both vitamins K

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and C; in addition, its synthesis is induced by

vitamin D.

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? The release into the circulation of osteocalcin

provides an index of vitamin D status.

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.
2.Matrix Gla protein- .

? MGP has been found in bone, cartilage, and soft

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tissue, including blood vessels.

? MGP prevents the calcification of soft tissues and

cartilages, while facilitating normal bone growth

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and development

3. Protein S-
? The vitamin K-dependent anticoagulant protein S
? Children with inherited protein S deficiency suffer

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complications related to increased blood clotting
as well as decreased bone density.
.

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4. Nephrocalcin in kidney
5. Product of the growth arrest specific gene

(Gas6)- which is involved in both the
regulation and differentiation and development

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of nervous system, and control of apoptosis in
other tissues.

6. Vitamin K is required for ETC and oxidative

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phosphorylation

- Vitamin K antagonists such as dicumarol act

as uncouplers of oxidative phosphorylation

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Vitamin K deficiency

Causes
? Lack of vitamin K in the diet
? Fat malabsorption

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? Disease or surgical interventions that affect the

ability of intestinal tract to absorb vitamin K

? Chronic liver diseases

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? Prolonged use of oral antibiotics
? Prolonged use of Warfarin
.

? Pre mature infants and new born babies

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- Transplacental transfer of vitamin K is very

limited during pregnancy,

-The storage of vitamin K in neonatal liver is

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also limited.

- Breast milk is a poor source of vitamin K.
- newborn infants to mother with poor vitamin

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K stores
Deficiency manifestations

? The main symptom is bleeding (hemorrhage)

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--into the skin (causing bruises),
--from the nose,
--from a wound,
---in the stomach, or
---in the intestine.

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? Blood may be seen in the urine or stool.
? Having a liver disorder increases the risk of

bleeding because clotting factors are made in

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the liver.

? Vitamin K deficiency may also weaken bones.
.

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? In newborns, life-threatening bleeding within

or around the brain may occur.

? Intracranial hemorrhage can occur during the

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delivery process and can lead to severe
complications.

? Soft tissue hemorrhages may be there.

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A deficiency of vitamin K can lead to extreme bleeding,
which can begin as a gum or nose discharge or bruising
Diagnosis

? A prolonged Prothrombin Time (PT) in the

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absence of liver disease is usually the first
laboratory test result to be abnormal in vitamin
K deficiency bleeding.

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? Prothrombin time is measured before and after

giving vitamin K in situation of doubt. If it
returns to normal after vitamin K injection, it
suggests vitamin k deficiency and rules out

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liver diseases. If not, liver disease is the likely
cause.
.

? Clotting Time

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The clotting time is usually between 6-8 minutes.
It is also increased in vitamin K deficiency
RDA

ADULTS - 50-100 g/day

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SOURCES

? Vitamin K is found in green leafy vegetables

such as kale and spinach

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? Appreciable amounts are also present in

margarine and liver.

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? Vitamin K is present in vegetable oils and is

particularly rich in olive, canola, and soybean
oils.

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? Some amount is contributed by intestinal

bacteria

Prevention

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? 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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? Intramuscular (IM) vitamin K prophylaxis at

birth is the standard of care.

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? These measures have served to make vitamin

K deficiency bleeding a rarity.
Hypervitaminosis K

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? Large dose (>5 mg) of menadione can cause

toxicity.

? Hypervitaminosis K leads to

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1. Hemolytic anemia
2. Jaundice ( hyperbilirubinemia and

kernicterus-leading to brain damage