Topic 10. Fat–soluble vitamins. Antioxidants.

manar behi 411b

The theoretical questions:
1. Fat-soluble vitamins, their structure and functions, participation in metabolism.Simptoms of
hypo- and hyper- vitaminoses.
Fat-soluble vitamins are a group of essential vitamins that are soluble in lipids and stored in
adipose tissue and the liver. There are four fat-soluble vitamins: A, D, E, and K.
Vitamin A:
Structure: Vitamin A is a group of compounds called retinoids, which include retinol, retinal, and
retinoic acid.
Functions: Vitamin A is important for vision, immune function, skin health, and cell growth and
development.
Participation in metabolism: Retinol is converted to retinal in the retina of the eye, which is
important for vision. Retinoic acid is involved in gene expression and cell differentiation.
Symptoms of hypovitaminosis A: Night blindness, dry skin, impaired immune function, and
delayed growth and development.
● Symptoms of hypervitaminosis A: Nausea, vomiting, dizziness, headache, and
liver damage.
Vitamin D:
Structure: Vitamin D is a group of compounds called secosteroids, which include vitamin D2
(ergocalciferol) and vitamin D3 (cholecalciferol).
Functions: Vitamin D is important for calcium and phosphorus absorption, bone health, and
immune function.
Participation in metabolism: Vitamin D is synthesized in the skin when exposed to sunlight. It is
converted to an active form in the liver and kidneys.
Symptoms of hypovitaminosis D: Weak bones, muscle weakness, and increased risk of falls and
fractures.
● Symptoms of hypervitaminosis D: Nausea, vomiting, constipation, and kidney
damage.
Vitamin E:
Structure: Vitamin E is a group of compounds called tocopherols, which include alpha-
tocopherol, beta-tocopherol, gamma-tocopherol, and delta-tocopherol.
Functions: Vitamin E is an antioxidant that protects cells from damage, and it may have a role in
immune function and neurological function.
Participation in metabolism: Vitamin E is absorbed in the small intestine and transported to the
liver, where it is incorporated into lipoproteins for distribution to other tissues.
Symptoms of hypovitaminosis E: Muscle weakness, vision problems, and neurological problems.
● Symptoms of hypervitaminosis E: Nausea, vomiting, diarrhea, and increased risk
 ●
of bleeding.
Vitamin K:
Structure: Vitamin K is a group of compounds called menaquinones (K2) and phylloquinone (K1).
Functions: Vitamin K is important for blood clotting and bone health.
Participation in metabolism: Vitamin K is produced by bacteria in the gut and is also obtained
from dietary sources. It is involved in the activation of proteins involved in blood clotting.
Symptoms of hypovitaminosis K: Excessive bleeding and bruising.
● Symptoms of hypervitaminosis K: None known.
It is important to consume a balanced diet that includes all essential vitamins to prevent
hypovitaminosis. However, consuming high doses of fat-soluble vitamins can lead to
hypervitaminosis, which can cause toxicity and other health problems. It is recommended to
speak to a healthcare provider before taking any vitamin supplements.

1.1. Role of bile acids in fat-soluble vitamin absorption, associated disorders

Bile acids are produced by the liver and stored in the gallbladder, and they play a crucial role in
the absorption of fat-soluble vitamins. When dietary fat enters the small intestine, bile acids are
released into the digestive tract to emulsify the fat, breaking it down into smaller droplets. This
process increases the surface area of the fat, allowing lipase enzymes to break it down further
into fatty acids and glycerol. Fat-soluble vitamins, which are also present in dietary fats, are
absorbed along with these fatty acids and glycerol.
Bile acids also play a role in the absorption of vitamin K, which is a fat-soluble vitamin produced
by gut bacteria. Vitamin K is incorporated into bile acids and then reabsorbed in the small
intestine along with the bile acids. This recycling process ensures that vitamin K is available for
blood clotting and other functions.
Disorders associated with bile acid production or function can affect the absorption of fat-
soluble vitamins. For example, liver disease can lead to decreased bile acid production, which
can impair the absorption of fat-soluble vitamins. Similarly, disorders that affect the gallbladder,
such as gallstones or inflammation of the gallbladder, can disrupt the release of bile acids and
impair fat absorption. Inflammatory bowel disease (IBD) can also affect bile acid function and
absorption of fat-soluble vitamins.
Additionally, some medications can affect bile acid function, leading to malabsorption of fat-
soluble vitamins. For example, drugs that bind to bile acids, such as cholestyramine, can
interfere with the absorption of fat-soluble vitamins.
Overall, bile acids play a crucial role in the absorption of fat-soluble vitamins, and disorders that
affect bile acid production or function can impair the absorption of these essential vitamins. It is
important to address any underlying medical conditions that may affect bile acid function and
absorption of fat-soluble vitamins to prevent deficiencies and associated health problems.
. 2. Vitamin A and other retinoids.
Vitamin A is a fat-soluble vitamin that is essential for human health. It is required for many
physiological processes, including vision, cell growth and differentiation, and immune function.
Vitamin A is obtained from the diet in the form of preformed vitamin A, also known as retinoids,
and provitamin A carotenoids, which are converted to vitamin A in the body.
Retinoids are a group of compounds that include retinol, retinal, and retinoic acid. Retinol is the
primary form of vitamin A found in animal-based foods such as liver, dairy products, and eggs.
Retinal is involved in vision and is derived from retinol in the retina of the eye. Retinoic acid is
involved in gene expression and cell differentiation.
Retinoids have a variety of important physiological roles. In addition to vision, retinoids are
involved in immune function, skin health, bone growth, and reproduction. Retinoic acid is
important in the regulation of cell growth and differentiation, and deficiencies in retinoids can
lead to skin problems, impaired immune function, and delayed growth and development.
However, excessive intake of retinoids can lead to toxicity, which can cause a variety of health
problems. Symptoms of hypervitaminosis A can include nausea, vomiting, dizziness, headache,
and liver damage.
In addition to retinoids, other synthetic retinoids have been developed for medical use. These
compounds, such as isotretinoin and acitretin, are used to treat skin disorders and other
conditions. However, they also have the potential for toxicity and should only be used under the
supervision of a healthcare provider.
Overall, retinoids are essential for human health, but it is important to maintain a balance
between intake and toxicity. A balanced diet that includes a variety of vitamin A sources can help
prevent deficiencies and excessive intake of retinoids.

2.1. Chemical nature, sources, daily requirement. Transport.

Chemical nature:
Vitamin A is a fat-soluble vitamin, which means that it dissolves in fats and oils, and not in water.
Vitamin A exists in several forms, including retinol, retinal, and retinoic acid.
Sources:
The primary sources of preformed vitamin A (retinoids) are animal-based foods, such as liver,
fish, eggs, and dairy products. Beta-carotene and other provitamin A carotenoids are found in
plant-based foods, such as carrots, sweet potatoes, spinach, and mangoes.
Daily Requirement:
The recommended daily allowance (RDA) of vitamin A varies depending on age, sex, and other
factors. For example, the RDA for adult males is 900 micrograms (mcg) of retinol activity
equivalents (RAE), while the RDA for adult females is 700 mcg RAE. However, the RDA for vitamin
A can be met through a combination of dietary sources of retinoids and provitamin A
carotenoids.
Transport:
Vitamin A is transported in the bloodstream bound to proteins, such as retinol-binding protein
(RBP) and transthyretin (TTR). These proteins protect vitamin A from oxidation and facilitate its
uptake by cells throughout the body. The liver is the primary storage site for vitamin A, where it is
stored as retinyl esters. When vitamin A is needed, it is released from the liver and transported to
tissues, where it is converted to the active forms of vitamin A, such as retinoic acid.
In summary, vitamin A is a fat-soluble vitamin that exists in several forms, including retinol,
retinal, and retinoic acid. It is found in animal-based foods as well as plant-based foods in the
form of provitamin A carotenoids. The recommended daily allowance varies depending on age,
sex, and other factors, and vitamin A is transported in the bloodstream bound to proteins such as
RBP and TTR.

2.2. Participation in metabolism. Disorders.

Vitamin A is involved in several metabolic processes in the body. One of the primary roles of
vitamin A is to support vision, as it is a component of the visual pigment in the retina of the eye.
Vitamin A is also important for maintaining healthy skin, as it helps regulate the growth and
differentiation of skin cells. It is also essential for immune function, as it supports the production
and activity of white blood cells that help fight infection.
Deficiencies in vitamin A can lead to a range of disorders. One of the most common is night
blindness, which is a condition where a person has difficulty seeing in low light conditions.
Vitamin A deficiency can also cause xerophthalmia, a condition where the surface of the eye
becomes dry and damaged, leading to blindness. Other symptoms of vitamin A deficiency can
include dry skin, weakened immunity, and delayed growth and development in children.
Excessive intake of vitamin A can also lead to toxicity, which can cause a range of symptoms,
including nausea, vomiting, dizziness, headache, and liver damage. Chronic vitamin A toxicity
can lead to bone problems, such as osteoporosis and fractures, as well as skin problems, such
as peeling and cracking.
Overall, vitamin A plays important roles in vision, skin health, immune function, and other
metabolic processes in the body. It is important to maintain a balance between intake and
toxicity to prevent deficiencies and excessive intake of vitamin A. A balanced diet that includes a
variety of vitamin A sources can help prevent deficiencies and promote overall health.

2.2.1.Visual cycle
The visual cycle is the series of biochemical reactions that occur in the retina of the eye in
response to light, resulting in the formation of visual signals that are sent to the brain. The visual
cycle is a complex process that involves several different molecules, including vitamin A, which
plays a critical role in the process.
The visual cycle begins when light enters the eye and strikes the retina, which is the part of the
eye that contains light-sensitive cells called photoreceptors. The photoreceptors contain
molecules called opsins, which are proteins that are sensitive to light. When light strikes the
opsins, it triggers a series of biochemical reactions that ultimately result in the formation of a
visual signal.
One of the key molecules involved in the visual cycle is a form of vitamin A called 11-cis-retinal.
11-cis-retinal is a component of the visual pigment rhodopsin, which is found in the rod cells of
the retina. When light strikes rhodopsin, it causes a change in the shape of 11-cis-retinal, which
triggers a series of reactions that ultimately lead to the formation of a visual signal.
After 11-cis-retinal has been converted to all-trans-retinal, it is transported out of the
photoreceptor cells to the adjacent retinal pigment epithelium (RPE) cells, where it is converted
back into 11-cis-retinal. This regenerated 11-cis-retinal is then transported back into the
photoreceptor cells, where it can once again be used to form visual signals in response to light.
Overall, the visual cycle is a complex process that involves several different molecules, including
vitamin A, which plays a critical role in the process. By understanding the visual cycle, scientists
can better understand the mechanisms underlying vision and develop new treatments for vision-
related disorders.

2.2.2. The role as a hormon.

In addition to its role in vision and other metabolic processes, vitamin A also functions as a
hormone in the body. The most active form of vitamin A, known as retinoic acid, interacts with
specific receptors in the nucleus of cells, where it can regulate gene expression and protein
synthesis.
Retinoic acid plays a critical role in a wide range of physiological processes, including embryonic
development, cell growth and differentiation, and immune function. For example, retinoic acid is
involved in the development of the nervous system, the formation of the limbs, and the
differentiation of cells in the skin and other tissues.
Retinoic acid also plays a role in regulating the immune system. It has been shown to modulate
the activity of several types of immune cells, including T cells, B cells, and macrophages. By
regulating immune cell activity, retinoic acid helps to promote immune function and prevent
autoimmune disorders.
Overall, vitamin A functions as a hormone in the body by interacting with specific receptors in
the nucleus of cells and regulating gene expression and protein synthesis. Retinoic acid, the
most active form of vitamin A, plays a critical role in a wide range of physiological processes,
including embryonic development, cell growth and differentiation, and immune function.

2.2.3. Antioxidant.
Vitamin A is a powerful antioxidant, which means that it can help protect the body against the
damaging effects of free radicals. Free radicals are unstable molecules that can damage cells
and tissues in the body, leading to a range of health problems, including cancer, heart disease,
and neurological disorders.
As an antioxidant, vitamin A helps to neutralize free radicals by donating an electron to the
unstable molecule, which stabilizes it and prevents it from causing damage to cells and tissues.
Vitamin A works in conjunction with other antioxidants, such as vitamin E and vitamin C, to
provide maximum protection against free radical damage.
In addition to its direct antioxidant effects, vitamin A also helps to support the production and
activity of other antioxidant enzymes in the body, such as superoxide dismutase and glutathione
peroxidase. By supporting the body's own antioxidant defenses, vitamin A helps to maintain
overall health and prevent disease.
Overall, vitamin A is an important antioxidant that helps to protect the body against the
damaging effects of free radicals. By neutralizing free radicals and supporting the body's own
antioxidant defenses, vitamin A helps to maintain overall health and prevent a range of health
problems.

3. Vitamin D and its role in calcium and phosphate homeostasis.

Vitamin D plays a crucial role in regulating calcium and phosphate homeostasis in the body.
Calcium and phosphate are important minerals that are involved in many physiological
processes, including bone formation, nerve function, and muscle contraction.
When dietary calcium and phosphate levels are low, or when there is an increased demand for
these minerals, the body relies on vitamin D to help absorb and transport them from the gut into
the bloodstream. Vitamin D stimulates the production of a protein called intestinal calcium-
binding protein, which helps to increase the absorption of calcium and phosphate from the gut.
Once calcium and phosphate are absorbed into the bloodstream, vitamin D helps to regulate
their levels by stimulating the production of parathyroid hormone (PTH). PTH acts on the bones
to release calcium and phosphate into the bloodstream, and also stimulates the kidneys to
reabsorb calcium and excrete phosphate.
In addition to its role in regulating calcium and phosphate homeostasis, vitamin D is also
important for bone health. It helps to stimulate the production of osteoblasts, which are cells that
help to build new bone tissue. Vitamin D also helps to maintain bone density by inhibiting the
activity of osteoclasts, which are cells that break down bone tissue.
Overall, vitamin D plays a critical role in regulating calcium and phosphate homeostasis in the
body. By helping to absorb and transport these minerals from the gut into the bloodstream, and
by regulating their levels in the bones and kidneys, vitamin D helps to maintain overall health and
prevent a range of health problems, including osteoporosis and rickets.

3.1. Chemical nature, sources, daily requirement.

Vitamin D is a fat-soluble vitamin that exists in several forms, the most important of which are
vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol). Vitamin D2 is found in plant-based
foods, while vitamin D3 is synthesized in the skin when it is exposed to sunlight.
Good dietary sources of vitamin D include fatty fish (such as salmon, mackerel, and tuna), egg
yolks, and fortified foods (such as milk, cereal, and orange juice). However, most people obtain
the majority of their vitamin D through exposure to sunlight.
The daily requirement for vitamin D varies depending on age, gender, and other factors. The
recommended dietary allowance (RDA) for vitamin D is 600 international units (IU) per day for
most adults, and 800 IU per day for adults over the age of 70. However, some experts
recommend higher daily intakes of vitamin D, especially for individuals who are at risk of
deficiency.
It is important to note that the body's ability to synthesize vitamin D from sunlight decreases
with age, and individuals who are housebound or have limited sun exposure may require
additional dietary sources of vitamin D to meet their daily requirements.
Overall, vitamin D is a fat-soluble vitamin that exists in several forms, including vitamin D2 and
vitamin D3. Good dietary sources of vitamin D include fatty fish, egg yolks, and fortified foods,
but most people obtain the majority of their vitamin D through exposure to sunlight. The daily
requirement for vitamin D varies depending on age, gender, and other factors, and individuals
who are at risk of deficiency may require additional dietary sources or supplementation.

3.2. Synthesis of 1,25(OH)2D3. Transport.

The synthesis of 1,25(OH)2D3 (also known as calcitriol) occurs primarily in the kidneys, although
small amounts may also be produced in other tissues. The process is regulated by a feedback
mechanism that involves the parathyroid gland and calcium levels in the blood.
The first step in the synthesis of 1,25(OH)2D3 is the production of vitamin D3 in the skin, either
through exposure to sunlight or consumption of dietary sources. Vitamin D3 is then transported
to the liver, where it undergoes hydroxylation to produce 25-hydroxyvitamin D3 (25(OH)D3),
which is the major circulating form of vitamin D.
The next step in the synthesis of 1,25(OH)2D3 occurs in the kidneys, where 25(OH)D3 is
converted to 1,25(OH)2D3 by the enzyme 1-alpha-hydroxylase. This conversion is regulated by a
feedback mechanism that involves the parathyroid gland and calcium levels in the blood. When
calcium levels are low, the parathyroid gland releases parathyroid hormone (PTH), which
stimulates the production of 1,25(OH)2D3. 1,25(OH)2D3 then acts on the intestines, bones, and
kidneys to increase calcium absorption, bone resorption, and calcium reabsorption, respectively,
in order to raise blood calcium levels.
Once synthesized, 1,25(OH)2D3 is transported in the blood to target tissues throughout the
body, including the intestines, bones, and kidneys. In these tissues, 1,25(OH)2D3 binds to
vitamin D receptors (VDRs), which are present on the surface of cells. The binding of
1,25(OH)2D3 to VDRs leads to changes in gene expression, which ultimately result in increased
calcium absorption and bone resorption.
Overall, the synthesis of 1,25(OH)2D3 is regulated by a feedback mechanism that involves the
parathyroid gland and calcium levels in the blood. Once synthesized, 1,25(OH)2D3 is transported
in the blood to target tissues throughout the body, where it binds to VDRs and regulates gene
expression to increase calcium absorption and bone resorption.

3.3. Participation in metabolism. Disorders.

Vitamin D plays a critical role in calcium and phosphate homeostasis and bone health. It helps
the body absorb calcium and phosphate from the intestines, and it stimulates bone growth and
remodeling. In addition, vitamin D is involved in a variety of other physiological processes,
including immune function, cell growth and differentiation, and insulin secretion.
Deficiency of vitamin D can lead to a variety of disorders, including rickets in children and
osteomalacia in adults, which are characterized by weak bones and increased risk of fractures.
Deficiency may also be associated with an increased risk of falls, muscle weakness, and
autoimmune diseases.
Excess intake of vitamin D can lead to hypervitaminosis D, which is characterized by
hypercalcemia (elevated levels of calcium in the blood) and can lead to kidney damage, vascular
calcification, and other adverse effects.
Overall, vitamin D plays an essential role in bone health and a variety of physiological processes,
and deficiency or excess can lead to a range of disorders. Maintaining adequate vitamin D status
through a balanced diet, appropriate sun exposure, and supplementation when necessary is
important for overall health and well-being.

4. Vitamin E. 4.1. Chemical nature, sources, absorption and daily requirement.

Vitamin E is a fat-soluble vitamin that exists in eight different forms, with alpha-tocopherol being
the most biologically active form. It is a powerful antioxidant that helps protect cells from
damage by neutralizing free radicals, which are unstable molecules that can damage cells and
contribute to chronic diseases.
Vitamin E is found in a variety of food sources, including vegetable oils, nuts and seeds, and
green leafy vegetables. The absorption of vitamin E in the intestine is dependent on the presence
of dietary fat and bile acids, and absorption can be impaired in individuals with fat malabsorption
disorders.
The daily requirement for vitamin E varies depending on age and sex, with adult men and women
requiring approximately 15 mg per day. Higher amounts may be required for individuals with
certain medical conditions or who engage in high levels of physical activity.
Overall, vitamin E is an important nutrient with antioxidant properties that plays a role in
protecting cells from damage. Adequate intake can be achieved through a balanced diet that
includes sources such as vegetable oils, nuts, and green leafy vegetables.

4.2. Participation in metabolism. Disorders.

Vitamin E plays a role in several metabolic processes, including acting as an antioxidant to
protect cell membranes from oxidative damage, helping to maintain the integrity of red blood
cells, and supporting immune function. It may also have a protective effect against chronic
diseases such as heart disease, Alzheimer's disease, and certain types of cancer.
Deficiency of vitamin E is rare but can occur in individuals with fat malabsorption disorders or
those with extremely low-fat diets. Symptoms of deficiency include muscle weakness, vision
problems, and impaired immune function.
Excess intake of vitamin E through supplementation can lead to adverse effects such as
gastrointestinal distress, impaired blood clotting, and increased risk of bleeding. It is important
to consume vitamin E through a balanced diet and avoid excessive supplementation.
Overall, vitamin E plays an important role in several metabolic processes and may have a
protective effect against chronic diseases. Deficiency is rare but can occur in certain individuals,
while excess intake through supplementation can lead to adverse effects.

5. Vitamin K, its participation in blood clotting.

Vitamin K is a fat-soluble vitamin that plays a critical role in blood clotting, also known as
coagulation. Blood clotting is a complex process that involves the activation of several different
clotting factors in a specific sequence. Vitamin K is required for the synthesis of several of these
clotting factors, including prothrombin and factors VII, IX, and X.
Vitamin K works by acting as a cofactor for an enzyme called gamma-glutamyl carboxylase,
which is responsible for adding a carboxyl group to specific amino acids in the clotting factors.
This carboxylation process is necessary for the clotting factors to bind to calcium ions and
participate in the clotting process.
Deficiency of vitamin K can lead to impaired blood clotting and an increased risk of bleeding,
especially in newborns who have not yet developed the ability to synthesize vitamin K.
Individuals taking certain medications, such as blood thinners, may also be at risk for vitamin K
deficiency.
Overall, vitamin K is essential for blood clotting and plays a critical role in the body's ability to
form clots and prevent excessive bleeding. Adequate intake of vitamin K through a balanced diet
that includes sources such as leafy green vegetables, broccoli, and vegetable oils is important
for overall health and well-being.

5.1. Chemical nature, sources and daily requirement.

Vitamin K is a group of fat-soluble vitamins that include phylloquinone (vitamin K1) and a group
of menaquinones (vitamin K2). Vitamin K1 is found in green leafy vegetables such as spinach,
kale, and broccoli, while vitamin K2 is synthesized by bacteria in the gut and is also found in
fermented foods such as cheese and natto.
The daily requirement for vitamin K varies depending on age and sex, with adult men and women
requiring approximately 90 to 120 micrograms per day. However, the actual requirements may be
higher in individuals taking certain medications, such as blood thinners, or those with medical
conditions affecting nutrient absorption or utilization.
Vitamin K is not generally found in multivitamin supplements, as adequate intake can usually be
achieved through a balanced diet. However, supplements containing vitamin K1 or K2 are
available for individuals with specific dietary needs or medical conditions.
Overall, vitamin K is an important nutrient for blood clotting and bone health. Adequate intake
can be achieved through a balanced diet that includes sources such as green leafy vegetables
and fermented foods. The daily requirement varies depending on age, sex, and individual health
status.

5.2. Participation in blood clotting. Disorders.

As mentioned earlier, vitamin K is essential for blood clotting. It plays a key role in the activation
of several clotting factors in a specific sequence. Vitamin K-dependent clotting factors include
prothrombin, factors VII, IX, and X.
Vitamin K deficiency can lead to impaired blood clotting, which can result in excessive bleeding
or hemorrhage. Newborns are particularly susceptible to vitamin K deficiency, as they are born
with very low levels of vitamin K and have not yet developed the ability to synthesize it. This is
why vitamin K injections are routinely given to newborns in many countries.
Vitamin K deficiency can also occur in individuals with fat malabsorption disorders or those
taking certain medications that interfere with vitamin K metabolism, such as blood thinners like
warfarin.
On the other hand, excessive intake of vitamin K is rare and usually only occurs with high-dose
supplementation. However, it can interfere with the effectiveness of blood thinning medications
like warfarin.
Overall, vitamin K is essential for blood clotting and deficiency can lead to impaired clotting and
excessive bleeding. Adequate intake can be achieved through a balanced diet, and
supplementation should only be used under medical supervision.