8/12/2019 02 Vitamin K

1/17

Biochemistry of Vitamin K

GIT | 1 Lecture | Dr. Usman Ghani

8/12/2019 02 Vitamin K

2/17

8/12/2019 02 Vitamin K

3/17

Types and Chemistry

Occurs in several forms:

Vitamin K1(Phylloquinone)

Vitamin K2(Menaquinone)

Vitamin K3(Menadione) synthetic form

8/12/2019 02 Vitamin K

4/17

Types and Chemistry

Vitamin K1(Phylloquinone)

Vitamin K2(Menaquinone)

Vitamin K3(Menadione)

8/12/2019 02 Vitamin K

5/17

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

8/12/2019 02 Vitamin K

6/17

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

8/12/2019 02 Vitamin K

7/17

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

8/12/2019 02 Vitamin K

8/17

Active form

Warfarin

8/12/2019 02 Vitamin K

9/17

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

8/12/2019 02 Vitamin K

10/17

Active form

Warfarin

8/12/2019 02 Vitamin K

11/17

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

8/12/2019 02 Vitamin K

12/17

Prothrombinplatelet interaction

8/12/2019 02 Vitamin K

13/17

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

8/12/2019 02 Vitamin K

14/17

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

8/12/2019 02 Vitamin K

15/17

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

8/12/2019 02 Vitamin K

16/17

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

8/12/2019 02 Vitamin K

17/17

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