N

I
M
A
T
I
V
MK-4

INTRODUCTION
RABIA MEHMOOD & NIAESH JAWED

CHEMISTRY (MENAQUINONE-4)
Vitamin K2 is part of a family of structurally similar fat-soluble, 2-methyl-1,4naphthoquinones derivatives that include phylloquinone (K1), menaquinones (K2),
and menadione (K3) that are needed for the posttranslational modification of
certain proteins required for blood coagulation and in metabolic pathways in bone
and other tissue.

These vitamin K2homologs are called menaquinones, and are characterized by the
number of isoprenoid residues in their side chains. Menaquinone-4 (abbreviated MK-4)
has four isoprene residues in its side chain.

Chemistry Vitamin K family are naphthoquinone derivatives . Phylloquinone and

menaquinones, both have a long isoprenoid side chain. The length of the side chain
differs. Phylloquinone have a 20 C side chain , whereas menaquinones have a 30 C side
chain. The isoprenoid chain makes these vitamin hydrophobic or lipophilic. The synthetic
vitamin K (menadione, menadiol diacetate) have only hydrogen in place of isoprenoid side
chain that makes these vitamin water-soluble.

SAR
naphthoquinone core is the structural motif responsible
for the neuroprotective activity and found that amine
substitution at the 2 carbon greatly enhanced the
protective activity. The further addition of a benzyl
group to the 2 amine improved the safety index of the
compound by completely abolishing anyin
vitroneurotoxicity, and chloro substitution at
themetaposition of the aromatic ring further improved
the protective potency of the compound.

KINETICS & DYNAMICS

AYEHSA IRSHAD BAJWA

MECHANISM OF ACTION
Themechanism of actionof vitamin K2 is similar to
vitamin K1. K vitamins play an essential role as
cofactor for the enzyme -glutamyl carboxylase,
which is involved in carboxylation of the vitamin Kdependent proteins specifically, the conversion of
peptide-boundglutamic acid(Glu) to -carboxy
glutamic acid (Gla).

PHARMACOKINETICS
ABSORPTION:

Absorption occurs in the upper small intestine .

The absorption of vitamin K2 require bile salts.

Transported from the mucosal cells to the liver by binding to chylomicrons .

STORAGE:

Vitamin K is stored in liver. Also present in significant amount in spleen and skeletal muscle

TRANSPORT:

Vitamin K released to the blood stream and transported in the blood by associating with beta-lipoproteins (LDL )

SOURCES & INDICATION

NATASHA NADIR

SOURCES & RECOMMENDATION

DIETARY SOURCES:
It
includes:
DIETARY
SOURCES:
food
ItAnimal
includes:
Ex.
meat,
Egg yolk, and milk.
Animal
food
Fermented
food.
Ex.
meat, Egg
yolk, and milk.
1.Animal
origin.
Fermented
food.
2.Plant
1.Animalorigin.
origin.
Ex.
cheese
and other fermented milk products.
2.Plant
origin.
Ex. cheese and other fermented milk products.
SUPPLEMENT:
MK-4 in supplement form is synthetic ,typically made
SUPPLEMENT:
from
extract ofform
plant
MK-4
inan
supplement
is Nicotiana
synthetic tabacum.
,typically made
from an extract of plant Nicotiana tabacum.
DAILY RECOMMENDATION:
MenRECOMMENDATION:
and women : 70 140 mcg.
DAILY
Children
: 35 75mcg
Men and women
: 70 140 mcg.
Children : 35 75mcg

INDICATIONS (MENAQUINONE-4)
Protecting Bone and Arterial Health with Vitamin K2

Vitamin K2
supports the
development and
maintenance of
bones and teeth
by enhancing
calcium and
phosphorus
absorption and
use.

Vitamin K2 is
essential for
correct calcium
metabolism: It
keeps calcium
where it belongs in the bones and
out of the blood
vessels

higher dietary
intake of vitamin
K2, especially the
MK-4 fraction, is
associated with a
reduced risk of
coronary
calcification
(plaque build-up)
and mortality
(death) from
coronary heart
disease.

Research suggests
that vitamin K2
supplementation
has a greater
effect in reducing
the risk of
coronary
calcification and
mortality from
coronary heart
disease compared
to vitamin K1.

OTHER INDICTAIONS
HINA AHMED

OTHER BENEFITS OF VIT K2:

A N T I - I N F L A M M A T O R Y

vitamin K's anti-inflammatory action. As the body ages, levels of the

inflammation-promoting cytokine interleukin-6 (IL-6) increase. Once IL-6
becomes out of balance with the other cytokines, inflammation accelerates. It
has been observed that people with arthritis, Alzheimer's disease, and
atherosclerosis have higher levels of IL-6 and are almost twice as likely to
develop mobility-related disabilities.

D I A B E T E S

The second highest concentration of vitamin K in the body is in the pancreas,

which plays a major role in blood sugar and insulin regulation. In animal
studies, Japanese researchers found that when they induced vitamin K
deficiency, the test animals developed Type II diabetes.

VIRAL CIRRHOSIS-R ELATE D LIVER C AN CER

Japanese researchers have recently discovered that vitamin K2 may play a
significant role in prevention of liver cancer caused by viral cirrhosis.

A N T I O X I D A N T

Research has indicated that vitamin K has antioxidant activity

comparable to vitamin E. Animal studies have demonstrated complete
hepatic (liver) protection from induced oxidative stress using vitamin K,
and was found to be 80% as effective as vitamin E in preventing
oxidation.
ALZHEIMER'S
About 25% of the population have a genetic predisposition for
developing Alzheimer's disease - they carry the E4 form of the
lipoprotein. Interestingly, people who carry this gene have been found
to have low levels of vitamin K. Calcification and the development of
lesions in blood vessels that feed the brain tissues are believed to be a
component of Alzheimer's development. Further research may reveal
high-dose vitamin K therapy to be preventive.

MENAQUINONE-4 DEFICIENCY
NABA ABBAS

DEFICIENCY (MENAQUINONE-4)
Itis very rare and occurs when there is an inability to absorb thevitaminfrom the intestinal
tract.
Vitamin K deficiency can also occur after prolonged treatment with oral antibiotics.

Deficiencyis often the result of impaired absorption rather than not getting enough in the diet.
Prolonged use of antibiotics can also cause a low level of this vitamin because they destroy some of
the bacteria in the gut that help to produce vitamin K.
Newborns are at risk for vitamin K deficiency.
This is because their digestive tracts contain no vitamin K-producing bacteria.
Vitamin K deficiency in adults is rare. When it occurs, it is found in people with diseases that
prevent the absorption of fat. These diseases include cystic fibrosis, celiac disease, and
cholestasis sometimes.

SYMPTOMS OF VIT K2 DEFICIENCY

Menstrualbleeding,gum bleeding,nose bleeding, and easybruising.
Bleedingwithin the digestive tract and blood in the urine.
Issues related to problematic blood clotting or bleeding, hemorrhaging.
Cartilage calcification.
Uncontrollable bleeding at surgical or puncture sites.
Brain bleeding in newborns.
Lack of Vitamin K2 causes calcium to fail to be deposited in bones where it belongs and to be deposited instead
in arteries, aorta, soft tissues including muscle, breast, kidneys and in heel spurs

TOXICITY & INTERACTIONS

HIRA KHAN

TOXICITY OF VITAMIN K2 (MENAQUINONE-4)

There is no
documented
case of
toxicity for
menaquinone

The European
Food Safety
Authoritys
safety
assessment of
menaquinone
concluded that
low doses of
menaquinone
presented no
safety concerns.

It is often
postulated
that
excessive
vitamin K
may result in
over
coagulation,
i.e.
increased
thrombosis
risk.

Despite this, it is
critical to
demonstrate
that a high
intake of
menaquinones
does not
increase
thrombosis risk.
It was shown in
rats that
thrombosis risk
is not increased
at doses up to
250 mg/kg of
MK-4.

The thrombosis
risk may only
occur in
individuals using
coumarin-based
oral
anticoagulants,
for whom dietary
supplementation
with vitamin K
can influence
the stability of
the international
normalised ratio.

In new born
theres a
risk of
hemolysis
in jaundice.

Toxic effects
of vit A and D
are
exacerbated
in presence
of vit K or E
deficiency.

INTERACTIONS OF VIT K WITH DRUGS AND FOOD

Orlistat and mineral

oil
can decrease
the
Orlistat
and mineral
absorption
of orallyoil can decrease
the
administered
absorption
of orallyVitamin K.
administered
Vitamin K.

Vitamin K can reduce

the
effects
of oral
anti
Vitamin
K can
reduce
likeanti
the coagulants
effects of oral
warfarin.like
coagulants
warfarin.

mineral oil can

decrease the
absorption of
orallyadministered
Vitamin K.