VITAMIN K
? "K " is the abbreviation of the German word
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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 dietarysource, 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 inthe 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 requiresvitamin K,O2 and CO2
? The formation of - carboxyglutamate is
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inhibited by dicumarol, an anticoagulant foundin 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 bodystores 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 aEpoxide 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-translationalmodification 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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vitaminK-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 osteocalcinprovides 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 development3. 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 kidney5. 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 inother 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 deficiencyCauses
? Lack of vitamin K in the diet
? Fat malabsorption
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? Disease or surgical interventions that affect theability 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 verylimited 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 withinor 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 aftergiving 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 likelycause.
.
? 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 isparticularly rich in olive, canola, and soybean
oils.
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? Some amount is contributed by intestinalbacteria
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 vitaminK deficiency bleeding a rarity.
Hypervitaminosis K
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? Large dose (>5 mg) of menadione can causetoxicity.
? Hypervitaminosis K leads to
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1. Hemolytic anemia2. Jaundice ( hyperbilirubinemia and
kernicterus-leading to brain damage
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