Vitamin K was discovered in 1929 when researchers observed that chickens fed a diet lacking a specific fat experienced bleeding issues. It plays a key role in blood clotting as a cofactor in the production of clotting factors. Vitamin K exists in different forms and comes from plant and animal sources. It is involved in the carboxylation of glutamic acid residues in proteins essential for blood clotting and bone health like osteocalcin. Deficiency can result in bleeding issues but is rare due to dietary sources and intestinal bacteria synthesis.
3. • Overview of Vitamin K
• Vitamin K, one of the fat-soluble vitamins, was
discovered relatively late. In 1929, researcher Henrik
Dam observed that chickens fed a diet lacking a specific
type of fat experienced bleeding in various tissues and
had a prolonged blood clotting time. Initially, it was
mistaken for scurvy or a response to a dietary toxin, but
neither theory proved correct. Further research revealed
that the inclusion of plant sterols prevented the disease,
demonstrating it was a nutrient deficiency. Dam named
the substance "vitamin K" because it helped with blood
clotting (from the German word "koagulation"). Vitamin
K's importance in blood clotting and its discovery through
animal studies mark significant milestones in our
understanding of this vital nutrient
4. • Structure and nomenclature
• Vitamin K comes in different forms, including K1 and K2,
which were isolated from different sources. Bacteria in
the intestines of animals, such as rats and chickens, can
produce vitamin K. The K1 family includes compounds
with a phytyl moiety at position 3, with phylloquinone
being the most important member. K2 compounds,
derived from animals, have varying side-chain lengths.
K3 compounds, lacking a side chain, can be synthesized
in the laboratory. When consumed, K3 compounds are
converted to K2 by intestinal bacteria. Vitamin K requires
a methyl group at carbon 2, a side chain at carbon 3, and
an unsubstituted benzene ring for its activity. Compounds
with a 20-carbon side chain have optimal activity. The
natural form is all-trans-all-trans-phylloquinone, while
synthetic phylloquinone is a mixture of cis and trans
forms.
5. • Chemical and Physical Properties
• Phylloquinone (K 120) is a yellow viscous oil. The
physical state of menaquinone (K2 20) depends
• on its side-chain length. If the side chain is 5 or 10
carbons long it is an oil, if longer it is a solid.
• Menadione (K3) is a solid. All three families of
compounds are soluble in fat solvents. Menadione can
be made water soluble by converting it to a sodium salt.
All the vitamin K compounds are
• stable to air and moisture but unstable to ultraviolet light.
They are also stable in acid solutions but are destroyed
by alkali and reducing agents. These compounds
possess a distinctive absorption spectra because of the
presence of naphthaquinone ring system.
6.
7. • Functions:
• Vitamin K was initially known for its role in
blood clotting. However, we now understand
that it serves as a vital cosubstrate for a
group of proteins involved in blood
coagulation and other functions. These
proteins include blood clotting factors II, VII,
IX, and X, as well as bone Gla protein,
osteocalcin, and plasma proteins C and S.
8. • Blood clotting is a complex process that
involves multiple phases. These phases include
the formation of thromboplastin, activation of
thromboplastin, formation of thrombin, and
formation of fibrin. When an injury occurs,
fibrinogen, a blood protein, is transformed into
fibrin, which forms a network of fibers to create
a blood clot. The transformation of fibrinogen to
fibrin is catalyzed by thrombin, which is derived
from prothrombin. For this transformation to
occur, prothrombin and the protease factor Xa
need to adhere to damaged cell phospholipids
with the help of calcium bridges.
9. • Carboxylation, a process that adds a specific
chemical group to proteins, is crucial for the
formation of these calcium bridges and the
adherence of prothrombin to damaged cell
walls. Phospholipids, specifically phosphatidyl
choline, play a role in the carboxylase enzyme
system required for carboxylation. The
synthesis of thrombin from prothrombin relies
on prothrombinase, active preaccelerin, and the
phospholipid cephalin. These factors are
activated by convertins found in blood and
tissues, representing the synthesis and
activation of the thromboplastin complex.
10. • To avoid confusion in the understanding of
blood coagulation, a numerical system was
established to designate various factors
involved. Four of these factors (II, VII, IX,
and X) are proteins synthesized in the liver
and dependent on vitamin K. Calcium ions
are necessary for their activation and
participation in the coagulation process.
11.
12. • importance of vitamin K in various biochemical processes and its impact on
protein function.
• Vitamin K acts as a cosubstrate in the carboxylation of proteins.
It undergoes metabolism in the liver.
There are two pathways for vitamin K reduction: the epoxi-quinone cycle and DT
diaphorase/microsomal dehydrogenase.
• Niacin and riboflavin are needed for the metabolism of vitamin K.
• Vitamin K is reduced to vitamin KH2 (hydroquinone) using NADH as a
coenzyme.
• Vitamin K quinone reacts with CO2 and O2 for the carboxylation of glutamyl
residues.
• Warfarin (coumarin) interferes with vitamin K reduction and epoxide conversion
• Vitamin K epoxide can substitute for vitamin K in carboxylation and prothrombin
synthesis.
• Glutamic acid and aspartic acid residues can be carboxylated.
• Proteins require the carboxylation of specific amino acid clusters to function
properly.
•
13. • Vitamin K is not only important for blood
clotting but also plays a role in bone health.
There is a protein called osteocalcin found in
bones, and it relies on vitamin K for its
proper functioning. Osteocalcin helps with
bone mineralization, which is essential for
strong and healthy bones. Vitamin K enables
osteocalcin to bind to calcium and other
minerals, allowing it to carry out its role in
bone formation. So, vitamin K is crucial for
both blood clotting and bone health.
14.
15. • Vitamin K is involved in regulating calcium
levels in bones and kidneys. Two proteins,
bone Gla protein (BGP) and a γ-carboxy-
glutamic acid-rich protein in the kidneys,
depend on vitamin K for their function. BGP
helps with bone mineralization, while the
kidney protein helps bind and conserve
calcium. However, if these proteins become
too active, it can lead to the formation of
kidney stones. The exact relationship
between the carboxylated peptide and stone
formation is not yet understood.
16. • Vitamin K deficiency
• The deficiency of vitamin K is uncommon, since it is present in
the diet in sufficient quantity and/or is adequately synthesized by
the intestinal
• bacteria. However, vitamin K deficiency may occur due to its
faulty absorption (lack of bile salts), loss of vitamin into feces
(diarrheal diseases) and administration of antibiotics (killing of
intestinal flora).
• Vitamin K deficiency can occur due to impaired absorption from
biliary disease, long-term antibiotic therapy, or the use of
anticoagulant medication. The main characteristic of deficiency is
a delayed clotting time and increased bruising. A test measuring
under-γ-carboxylated prothrombin and decreased urinary
excretion of γ-carboxyglutamic acid can detect deficiency. In
women, vitamin K deficiency may be linked to osteoporosis and
atherosclerosis, as it plays a role in calcium homeostasis.
Newborn infants may also experience delayed clotting times, but
routine administration of vitamin K to pregnant women is no
17. • Antagonists of vitamin K
• The compounds—namely heparin, bishydroxy-coumarin—
act as anticoagulants and are antagonists to vitamin K. The
salicylates and dicumarol are also antagonists to vitamin K.
• Dicumarol is structurally related to vitamin K and acts as a
competitive inhibitor in the synthesis of active prothrombin.
18. • Dietary sources
• Phylloquinone is the primary form of dietary vitamin
K found in humans. It is abundant in alfalfa, which
has been known for its high vitamin K content. When
studying the vitamin K content of common foods
using the chick bioassay method, it has been
observed that green leafy vegetables contain
significant amounts of vitamin K, meats and dairy
products contain moderate amounts, while fruits and
cereals contain smaller amounts.
• Cabbage, cauliflower, tomatoes, alfa alfa,
• spinach and other green vegetables are good
sources. It is also present in egg yolk, meat, liver,
cheese and dairy products