02 vitamin k
TRANSCRIPT
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Biochemistry of Vitamin K
GIT | 1 Lecture | Dr. Usman Ghani
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Types and Chemistry
Occurs in several forms:
Vitamin K1(Phylloquinone)
Vitamin K2(Menaquinone)
Vitamin K3(Menadione) synthetic form
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Types and Chemistry
Vitamin K1(Phylloquinone)
Vitamin K2(Menaquinone)
Vitamin K3(Menadione)
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Sources of Vitamin K
Phylloquinone: Green leafy vegetables
Menaquinone: Intestinal bacteria
Intestinal bacterial synthesis meets the daily
requirement of vitamin K even without dietary
supplement
Menadione: synthetic form
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RDA for Vitamin K
(g/day) Infant (0-1 year): 2-2.5
Children (1-8): 30-55
Men (19+): 120 Women (19+): 90
Pregnancy / lactation: 90 / 90
UL: Not established
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Functions of
Vitamin K
Coenzyme for the synthesis of
prothrombin and blood clotting
factors in the liver
Prothrombin and clotting factors are
protein in nature
Synthesis of prothrombin, clotting
factors VII, IX, X require carboxylation
of their glutamic acid (Glu) residue
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Active form
Warfarin
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Functions of
Vitamin K
Mature prothrombin and clotting factors
contain g-carboxyglutamate (Gla) after
carboxylation reaction Vitamin K is essential for the
carboxylase enzyme involved
Dihydroquinone form of vitamin K isessential for this reaction
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Active form
Warfarin
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Functions of
Vitamin K
Anticoagulant drugs: warfarin and dicoumarol
Structural analogs of vitamin K
They inhibit the activation of vitamin K to
hydorquinone form
Hence prothrombin and clotting factors are not
carboxylated
Blood coagulation time increases upon injury
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Prothrombinplatelet interaction
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Functions of Vitamin K
Prothrombin
platelet interaction Carboxylated prothrombin contains two
carboxylate groups (COO)
These groups bind to Ca2+forming
prothrombin-calcium complex
The complex then binds to phosholipids on
the surface of platelets (important for blood
clotting)
Converting prothrombin to thrombin and
initiating clot formation
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Functions of
Vitamin K
Synthesis of g-carboxyglutamate in
osteocalcin
Osteocalcin is a bone protein May have a role in bone formation and
mineralization
g-carboxyglutamate is required for osteocalcin
binding to hydroxyapatite (a mineral) in thebone
The function of bone osteocalcin is unclear
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Deficiency of Vitamin K
Deficiencies are rare: it is synthesized bythe intestinal bacteria
Hypoprothrombinemia: increased bloodcoagulation time
May affect bone growth andmineralization
Malabsorption of lipids leads to vitamin Kdeficiency
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Deficiency of Vitamin K
Prolonged antibiotic therapy
Gastrointestinal infections with diarrhea
Both of the above destroy the bacterial flora
leading to vitamin K deficiency Deficiency most common in newborn
infants
Newborns lack intestinal flora Human milk cannot provide enough vitamin K
Supplements are given by injection
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Clinical Manifestations of the
Deficiency Hemorrhagic disease of the newborn
Bruising tendency, ecchymotic patches (bleedingunderneath the skin)
Mucus membrane hemorrhage
Post-traumatic bleeding / internal bleeding
Prolonged prothrombin time