Transcript Vitamin K 1

Vitamin A and Carotenoids
Ancient Egyptians recognized that night blindness could
be treated by consumption of liver.
In the late 1920’s through the efforts of a Swiss scientist
named Karrer and his colleagues, the fat-soluble compound
in liver was isolated and termed vitamin A.
Vitamin A is Fat-soluble alcohol, most abundant in fatty
fish and especially in fish-liver oils.
It is not found in plants, but many vegetables and fruits
contain β-carotene which is readily converted in the body
to vitamin A (Provitamin).
7
5
CH2OH
4
6
3
Vit.A1:
all-trans-Retinol
8
CH3
7
4
6
3
1
2
8
CH3
11
9
10
12
14
CH3
11
15
13
CHO
all-trans- Retinal
CH3
5
15
13
CH3
1
2
11
9
CH2OH
10
12
14
CH3
Vit. A2: All - trans- 3-DehydroRetinol
CH3
H3C
CH3
CHO
11-cis-Retinal
Light cause isomerization of 11-cis to all-trans
isomer resulting in activation of the
photoreceptor molecule.
Sources

Vitamin A1:
A yellow crystalline compound found in:
Egg yolks, Milk, and Cod-liver oil.

Vitamin A2 :
A golden yellow oil Found in:
Livers of fresh water fish
(40 % of the biological activity of vitamin A1).
Carotenoids

They are known as Provitamin A as they
converted in the body to vitamin A. They
are mostly found in plants.

Plant Carotenoids are found in:
Carrots, Apricots, Asparagus, Broccoli, and
Green leafy vegetables.
Special strain of rice “Golden Rice are rich
in b-carotene.
Role of Vit. A

Vision:
Vitamin A is the chromophore of rhodopsin (vertebrate
photoreceptor molecule) used in low light levels.
Rhodopsin is a complex of Vit. A and Opsin protein present
in the retina.

Epithelial Cells:
Vitamin A is essential for the epithelial cells. In Vitamin A
deficiency, mucus-secreting cells are replaced by keratin
producing cells, leading to xerosis.

Glycoprotein synthesis:
Glycoprotein synthesis requires Vitamin A. In severe
Vitamin A deficiency, lack of glycoproteins may lead to
corneal ulcers or liquefaction.
Immune System:
Vitamin A is essential to maintain intact epithelial tissues as a physical
barrier to infection, maintaining a number of immune cell types. These
include the lymphocytes (B-cells, T-cells, and natural killer cells), as
well as many myelocytes (neutrophils, macrophages, and myeloid
dendritic cells).
Formation of red blood cells:
Vitamin A may be needed for normal haematopoiesis; deficiency
causes abnormalities in iron metabolism.
Growth:
Vitamin A affects the production of human growth hormone (GH).
Recommended Daily Amount (RDA)


900 micrograms/day, or 3,000 IU for a 25year old male.
1 IU of retinol is equivalent to 0.3 μg.
Deficiency

Night blindness: Is one of the first signs of vitamin A
deficiency. Vitamin A deficiency contributes to blindness
by making the cornea very dry and damaging the retina
and cornea.


Impaired Immunity: Vitamin A deficiency also
diminishes the ability to fight infections causing frequent
infections (especially respiratory). In countries where
children are not immunized, infectious disease like
measles have relatively higher fatality rates.
Symptoms of deficiency may include, loss of appetite,
hair loss, rashes, dry skin and eyes, poor growth, and
fatigue.
Uses



Treatment of Night blindness.
Skin Diseases:
 Psoriasis
 acne vulgaris
 Keratosis pilaris
Cosmetics: vitamin A derivatives are used as so-called antiaging chemicalsvitamin A is absorbed through the skin and increases the rate of skin turnover, and
gives a temporary increase in collagen giving a more youthful appearance.


promote development of bones and soft tissues and
sperm production.
protects against bladder cancer, lung cancer (aerosol
form ).
Products

Tretinoin : Retinoic acid: Retin-A: Retinoic acid
Isotretinoin: Accutane
 Etretinate: Tegison

Risk Factors for Deficiency
Under certain circumstances some individuals may require higher
doses of vitamin A as following:
1- Those who consume alcoholic beverages may be more
liable to vitamin A deficiency.
2- People taking some medications, including birth
control pills, methotrexate, cholestyramine, colestipol,
and drugs that act to sequester bile acids.
3- Those who are chronically ill, recovering from
surgery or other injuries.
4- Patients undergoing treatments for cancer (radiation
and chemotherapy).
5- Other conditions that may impair vitamin A balance
including chronic diarrhea, cystic fibrosis, and kidney
or liver disease.
6- Diabetics persons are often deficient in vitamin A.
Vitamin A Toxicity
1- High level of carotenoid ( β-carotene) was associated with
an increase risk of lung cancer in male smokers. In nonsmokers, the opposite effect has been noted.
2- Excess vitamin A during early pregnancy has also been
associated with an increase in birth defects (Terratogenic
effects). No more than 5,000 IU per day.
3- Tingling and itchy feeling due storage of excessive amounts
of vitamin A in fat cells.
Symptoms of Vit. A toxicity include:
 Dry lips and skin.
 Bone and joint pain.
 Blurred or double vision.
 Confusion and fatigue.
liver and spleen enlargement.
Diarrhea, vomiting, headaches.
Soft spot on the head in infants.
Very high levels of vitamin A may also create
deficiencies of vitamins C, E, and K.
Drug Interactions
Vitamin A supplements should not be taken in
conjunction with any retinoid medications, due to higher
risk of toxicity.
Using of mineral oil impairs absorption of all the fatsoluble vitamins, including A.
Aluminum-containing antacids and cholesterol-lowering
drugs (cholestyramine and colestipol) may
inhibit
absorption vitamin A
Alcohol, barbiturates, caffeine, cortisone, tobacco, and
very high levels of vitamin E deplete the body of Vitamin
A.
Overuse of alcohol and vitamin A together may increase
the possibility of liver damage.
Vitamin C, vitamin E, Zinc, and Selenium optimizes
absorption and use of vitamin A and carotenoids.
Iron deficiency anemia is better treated with a
combination of iron supplements and vitamin A than with
iron alone.
Vitamin D



Vitamin D is a generic description of a group of
compounds have equivalent activity.
On of the fat soluble vitamins.
Know as Sunshine vitamin as it is formed by
the effect of UV rays during the midday from
sterols.
Forms of Vitamin D





Vitamin D1: Mixture of ergocalciferol with
lumisterol 1:1
Vitamin D2: ergocalciferol or calciferol (made
from ergosterol)
Vitamin D3: cholecalciferol (made from 7dehydrocholesterol)
Vitamin D4: 22,23-dihydroergocalciferol
Vitamin D5: sitocalciferol (made from 7dehydrositosterol)
D2
Vitamin D2 = Ergocalciferol (Deltalin®)
D3
Vitamin D3 = Cholecalciferol
Sources



Code liver oil
Tuna
Sardines
Biosynthesis
UV Light
HO
HO
7-dehydrocholesterol
pre-vitamin D3
Isomerization
Calcitriol
OH
25-hydroxycholecalciferol (calcidiol)
formed and stored in the liver
The main biologically active form
1,25-dihydroxycholecalciferol
(calcitriol) formed in the Kidney.
HO
OH
HO
Vitamin D3
(cholecalciferol)
Role of Vit D
Vitamin D has the net effect of increasing the
serum calcium and phosphate concentrations by:
1- By increasing intestinal calcium and phosphate absorption
and reabsorption from the kidney.
2- increasing the effect of parathyroid hormone (PTH) on
bone.
Controls parathyroid gland growth and
production of the parathyroid hormone.
Treatment of rickets and osteomalacia.
It is an immunomodulator.
Regulation of insulin production.
It is required for female reproduction.
Recommended Daily Amount (RDA)


10 mg Cholecalcifrol = 400 IU.
Materno-fetal transfer of vitamin D is mostly in
the form of calcidiol (25-OH vitamin D), which
readily crosses the placenta. The half-life of
calcidiol is approximately three to four weeks.
Thus, the serum concentration of vitamin D falls
rapidly after birth unless additional sources are
available.
Causes of deficiency
Vitamin D deficiency can occur as a result of:
Decreased intake or absorption,
 Reduced sun exposure,
 Increased hepatic catabolism,
 Decreased endogenous synthesis (via 25hydroxylation in the liver and subsequent 1hydroxylation in the kidney).
 End-organ resistance to vitamin D .

Diseases caused by deficiency

Vitamin D deficiency is known to cause several
bone diseases including:




Rickets: a childhood disease characterized by failure of
growth and deformity of long bones.
Osteoporosis: a condition characterized by fragile bones.
Osteomalacia: a bone-thinning disorder in adults that is
characterised by proximal muscle weakness and bone
fragility. Osteomalacia can only occur in a mature
skeleton.
Vitamin D malnutrition may be linked to chronic
diseases such as

cancer (breast, ovarian, colon, prostate, lung and skin
cancer), chronic pain, several autoimmune diseases, high
blood pressure, depression, and seasonal affective
disorder
Rickets

Rickets is a softening of the bones in children
potentially leading to fractures and deformity. Rickets is
among the most frequent childhood diseases in many
developing countries. The predominant cause is a
vitamin D deficiency, but lack of adequate calcium in
the diet may also lead to rickets.
Osteoporosis
Osteoporosis is a disease in which bones
become fragile and more likely to break. If not
prevented or if left untreated, osteoporosis can
progress painlessly until a bone breaks. These
broken bones, also known as fractures, occur
typically in the hip, spine, and wrist
Osteomalacia

Osteomalacia is a softening of the bones,
resulting from defective bone mineralization. It
may show signs as pain, weakness, and fragility
of the bones. This is caused from the lack of
Vitamin D in adults, or Rickets in children
Groups at greater risk
Older people (age 50 and over) have a higher risk of
developing vitamin D deficiency because:
a- The ability of skin to convert 7-dehydrocholesterol
to pre-vitamin D3 is decreased in older individuals.
b- The kidneys, which help convert calcidiol to its
active form, sometimes do not work well.
Newborn infants who are exclusively breastfed require
vitamin D supplements. Breast milk does not contain
significant levels of the vitamin. Infant formula is generally
fortified with vitamin D. so this requirement only applies to
breastfed infants.

Those who avoid or are not exposed to summer
midday sunshine may also require vitamin D
supplements.

Dark-skinned individuals may require extra vitamin
D because melanin acts like a sun-block, prolonging
the time required to generate vitamin D.

Obese people have lower levels of the circulating form
of vitamin D, probably because it is deposited in body
fat compartments and is less bioavailable.

Patients with chronic liver disease or intestinal
malabsorption , parathyroid glands removed
General Use of Vitamin D
1- Prevent and treat osteoporosis as a result of calcium depletion.
Treatment require taking both calcium and vitamin D. fractures.
2- Osteomalacia and rickets are also effectively prevented and treated
through adequate vitamin D supplementation.
3- Vitamin D also has a role in cancer prevention (colon cancer, breast
and prostate cancer). The action of Tamoxifen (Chemotherapeutic
agent) appears to be improved with small added doses of vitamin D.
4- Treatment of hearing loss resulted from vitamin D deficiency that
affect the function of small bones in the ear responsible sound
transmition.
5- In combination with phosphate to treat some metabolic
diseases as Fanconi syndrome and familial hypophosphatemia.
Fanconi syndrome: is a disorder in which the proximal tubular
function of the kidney is impaired, resulting in decreased
reabsorption of electrolytes and nutrients back into the
bloodstream. Compounds involved include glucose, amino acids,
uric acid, phosphate and bicarbonate.
Familial hypophosphatemia: is a rare inherited disorder
characterized by impaired transport of phosphate and altered
vitamin-D metabolism in the kidneys. In addition, calcium and
phosphate are not absorbed properly in the intestines, which can
lead to softening of bones.
6- A topical form of vitamin D can be helpful in the
treatment of plaque-type psoriasis (Oral doses of
vitamin D are not effective).
Side Effects

Minor side effects are poor appetite, constipation, dry
mouth, increased thirst, metallic taste, or fatigue.

Other reactions are headache, nausea, vomiting,
diarrhea, or confusion.
Interactions
1- The absorption of vitamin D is improved by calcium, choline,
fats, phosphorus, and vitamins A and C.
2- Rifampin, H2 blockers, barbiturates, heparin, isoniazid,
colestipol,
cholestyramine,
carbamazepine,
phenytoin,
fosphenytoin, and phenobarbital reduce serum levels of vitamin D
and increase its metabolism.
3- Overuse of mineral oil and stimulant laxatives may deplete
vitamin D.
4- Osteoporosis and hypocalcemia can result from prolonged use
of corticosteroids. It is necessary to take of calcium and vitamin D
together with corticosteroid drugs.
5- The use of thiazide diuretics with vitamin D can cause
hypercalcemia in individuals with hypoparathyroidism.
6- Concomitant use of digoxin or other cardiac glycosides with
vitamin D may lead to hypercalcemia and heart irregularities.
Vitamin E
A group of compounds (α, β, γ, and δ-tocopherols)
with a chromanol ring and phytyl side chain. They
have the activity equivalent to d-a-tocopherol.
CH3
H3C
O
CH3
CH3
CH3
CH3
CH3
HO
6
CH3
Phytyl side chain
Chromanol group
Sources

Natural sources: Natural vitamin E (RRR-a-tocopherol)



present in plants only mainly the leaves of green vegetables.
Vegetable oils (wheat germ, sunflower, cottonseed, safflower,
soybean, and corn oil) .
Unprocessed grains, nuts.

Synthetic sources all racemic-tochopherol.

Gastrointestinal absorption of all forms of vitamin E is equivalent.
the subsequent physiological steps are sharply in favor of the RRR
form. The cellular liver transfer protein that maintains the plasma
level is specific for the RRR form of α -tocopherol. It selectively
choosing the RRR form and bind it into plasma lipoproteins for
distribution of the vitamin to every tissue and organ in the body.
Recommended Daily Amount (RDA)
d-a-tocopherol Equivalent (TE):
1 TE = 1 mg = 1.5 IU
30 IU commercial products, however it is safe
so larger doses are allowed.

Role of Vitamin E

Vitamin E has a very important role in normal cells
metabolism. It protects with other nutrient (Vitamin C
and Selenium) against he damaging free radicals
formed during metabolism of fatty acids.
Causes of deficiency



Insufficient dietary intake.
Impaired absorption.
Other factors:
Deficiency of Riboflavin and cystein.
 Deficiency of minerals like Cu, Zn and Mg.

Uses


Cancer prevention and treatment: Vitamin E is a known
antioxidant reduces risk of Cancer. High doses of dietary
antioxidants may increase the efficacy of the radiation
treatment and protects healthy cells against damage.
Immune system stimulation: Especially in elderly patients,
boosts immune system function. It also slow disease
progression in HIV-positive patients.

Eye disease prevention: Reduces the risk for
cataracts and for macular degeneration,
particularly among women.

Macular degeneration: is a medical condition predominantly
found in elderly adults in which the center of the inner lining
of the eye, known as the macula area of the retina, suffers
thinning, atrophy, and in some cases bleeding.
A cataract is a condition of clouding lens of the eye.
A patient who is blind from cataracts might have
white not clear corneas. Lens clarity was better in
regular users and higher blood levels of vitamin E.

Memory loss prevention.

Alzheimer's disease (AD) treatment: Alzheimer's patients
who took daily vitamin E maintained normal functioning
longer than patients who took a placebo. High dietary
intake of vitamin E lowers the risk of developing AD.

Diabetes treatment: Vitamin E reduces the symptoms of
diabetic neuropathy and to improve the speed of
transmission of nerve impulses.

Pain relief: Vitamin E acts as both an anti-inflammatory
and analgesic. It may be useful in arthritis pain in some
individuals.
Vitamin
E may protect the liver against disease.
Parkinson's disease prevention: High doses of vitamin E
lowered risk of developing Parkinson's disease.
Heart disease prevention:Vitamin E may prevent heart disease
by lowering total blood cholesterol levels and preventing
oxidation of LDL cholesterol.
Skin care: Vitamin E is thought to increase an individual's
tolerance to UV rays when taken with vitamin C and to promote
faster healing of wounds.
Side Effects
Vitamin E is well-tolerated, and side effects are rare. However, in
some individuals who are vitamin K deficient, vitamin E may
increase the risk for hemorrhage or bleeding.
Vitamin E ointments, oils, or creams may trigger an allergic
reaction known as contact dermatitis.
Interactions
Vitamin E can alter the efficacy of anticoagulant or
anticonvulsant drugs.
Vitamin E increase bleeding time in patient taking herbal
preparations as Feverfew or Gingko Biloba.
Inorganic iron supplements destroy vitamin E, so individuals
taking iron supplements should space out their doses (e.g., iron
in the morning and vitamin E in the evening).
Large doses of vitamin A can decrease the absorption of
vitamin E.
Alcohol and mineral oil can also reduce vitamin E
absorption, and these substances should be avoided in vitamin
E deficient individuals.
Vitamin K
(Antihemorrhagic factor)
A group of compounds derived from 2-methyl-1,4naphthoquinone that prevent bleeding in
mammals and birds.
Forms of Vitamin K:



Vitamin K1 (Phylloquinones, Phytonadione) is produced by
green plants.
Vitamin K2 (Menaquinones, MK) is produced by intestinal
bacteria.
Vitamin K3 (Menadione) is a synthetic compound.
Sources

Rich Food in Vitamin K:


Kale, Spinach, Turnip, Parsley and Mustard.
Food Moderate in Vitamin k:

Lettuce and Broccoli.
O
1
[
4
O
]
n
Vitamin K1 = Phytonadione
O
1
2
[
4
O
Vitamin K2(30) = Menaquinone-6
Vitamin K2(35) = Menaquinone-7
O
1
4
O
Menadione
]
n
n=4
n=5
Role of Vitamin K
Vitamin K (hydroquinone , the active form) is involved as a cofactor
in the carboxylation of certain glutamate residues in proteins to form
γ-carboxyglutamate residues (Gla-residues). Gla-residues are usually
involved in binding calcium. The Gla-residues are essential for the
biological activity of :

Blood coagulation: (factors II (prothrombin), IX, X , VII anticoagulant
proteins C and S, and the thrombin-targeting protein Z ) must be convered
to γ-carboxyglutamate and bind to Ca to form clot. This is the most
important role of Vitamin K.

Bone metabolism:



Bone Gla-protein Osteocalcin: Regulate incorporation of Calcium
Phosphate into bones.
Matrix Gla protein (MGP)]: Clearance of extracellular Calcium to
protect against soft tissue calcification.
Vascular biology.
Recommended Daily Amount (RDA)





Male: 80 mg/day
Female: 65 mg/day
New Born: 500- 1000 mg/day (Sterile intestine)
0- 6 Months: 5 mg/day
6- 12 Months: 15 mg/day
Commercial infant formula contain 50- 125 mg/day
Absorption

Vitamin K1 is absorbed through Active
transport mechanism.

Vitamins K2 and K3 are absorbed through
passive diffusion.
Metabolism

70% of Vit K3 excreted in urine in 24 hr in the
form of sulphate, phosphate and glucuronic acid
conjugate.

Small % excreted in faces as glucuronic acid
conjugate.

Vit K2 and K3 undergo slower metabolism to
shorten the side chain to 5- 7 carbons carboxylate.
Causes of Deficiency



Disturbed intestinal uptake (a bile duct
obstruction).
Therapeutic or accidental intake of vitamin Kantagonists.
Nutritional vitamin K-deficiency.
Deficiency

Uncontrolled internal bleeding.

Cartilage calcification
developing bone.

Deposition of insoluble calcium salts in the arterial
vessel walls.
and
malformation
of
Structure Activity Relationship (SAR)
O
A
1
CH3
B
4
O
Increase activity:


Ring A : a- Aromatic or hydro- aromatic.
Ring B is aromatic or hydro- aromatic.
b- Not substituted.
Decrease Activity:


Alkyl group larger than Methyl at C-2.
Hydroxyl group at C-3 or hydroxtlation of the side chain.
O
A
1
CH3
B
4
O

Activity not affected if positions 1 and 4 are:
OH
 O-Ac
 OCH3
 OC2H5
 C=O

Toxicity

Vitamins K1 and K2 are non-toxic in large doses.

Vitamin K3 is toxic in doses tree time more than the
usual dose.
Toxicity cause:



Hyperbilirubinemia.
Sever Jaundice.
Anemia.
Interaction

Some interactions may increase the need for
vitamin K:







Antibiotics: Prevent absorption and kill normal bacterial
folra.
Anticonvulsants: Affect the body ability to use Vit K.
Bile Acid Sequestrants (Cholestyramine) and Aspirin:
Affect absorption.
Mineral oil laxatives: Affect absorption.
Weight Loss Products (Orlistat and olestra): Affect
absorption as they prevent absorption of fats.
X-rays and Radiation: Deplete vitamin K levels and raise
vitamin K requirements.
Avoid high doses of vitamin K and food rich in
vitamin K when anticoagulants are used.