Vitamins-1

Fat soluble vitamins

Academic year (2023-2024)

Dr. Laila Mahdi Mohamed

Lecturer of Biochemistry and Molecular Biology
Faculty of Medicine-Helwan University
 Learning objectives
• Define vitamins and recognize their classification, their metabolism, sources
and requirements.
• Explain the functions and manifestations of deficiency of each vitamin,
correlating them with diseases caused by such deficiencies.
 Outlines
- Definition, classification & common features
- Fat Soluble Vitamins
✓Vitamin A
✓Vitamin K
✓Vitamin E
✓Vitamin D
Vitamins- Definition, classification & common features:
➢ Vitamins are organic compounds that cannot be synthesized in sufficient quantities by
human and must be obtained from diet.
➢ Vitamins classification:
Fat-soluble vitamins (A, K, E and D)
✓ They are hydrophobic compounds, absorbed with dietary fats.
✓ They are transported in the blood in lipoproteins (chylomicrons) or attached to specific
binding proteins.
✓ They are not readily excreted and are stored in the liver and adipose tissue.
✓ They more likely to accumulate in the body (more likely to lead to hypervitaminosis).
✓ Only vitamin K has a coenzyme function.
Water-soluble vitamins (9 vitamins, B complex and vitamin C)
✓ They are hydrophilic compounds dissolve easily in water, so they are excreted in urine,
not readily stored, toxicity is rare, but deficiencies can occur quickly.
✓ They function mainly as coenzymes for the enzymes of metabolism.
Fat Soluble Vitamins- Vitamin A

➢ Chemistry
➢ Dietary sources and requirements
➢ Functions
➢ Deficiency (causes & manifestations)
Fat Soluble Vitamins- Vitamin A, Chemistry
Chemistry of vitamin A (antixerophthalmic vitamin):
➢ Vitamin A is a collective term for several related biologically active
compounds called “Retinoids“
1- Retinol: A primary alcohol.
2- Retinal: The aldehyde derived from the oxidation of retinol.
Retinal and retinol are interconvertible.
3- Retinoic acid: Derived from oxidation of retinal and cannot be reduced in the
body.
➢ Provitamin A (Vit A precursor, Carotenoids)
- Yellow pigments present in plants (α, β and γ carotenes).
- The most important is β–carotene as it contains two β-ionone rings.
Fat Soluble Vitamins- Vitamin A, Chemistry
 Fat Soluble Vitamins- Vitamin A, Dietary sources and requirements

Dietary sources of vitamin A:

- Requirements , the recommended dietary allowance (RDA): For reading

2500 to 5000 IU/day for adult
6000 – 8000 IU/day for growing children, pregnancy & lactation (During pregnancy, a daily
supplement should not exceed 10,000 IU and a weekly supplement should not exceed 25,000
IU due to teratogenic effects of vitamin A).
- Absorption of Vitamin A: Like other dietary fats, Vit. A is absorbed as chylomicrons, uptaken
by the liver & transported to the extrahepatic tissues by retinol binding protein (RPB).
Fat Soluble Vitamins- Vitamin A, Functions

Functions of vitamin A:
❑ Regulation of cell growth and differentiation

❑ Maintenance of healthy epithelial tissues

❑ Healthy bone and teeth

❑ Normal reproduction

❑ Anticancer effect (Antioxidant action)

❑ Vision

Note: Retinoic acid mediates most of the functions of retinoids, except for
vision which depends on retinal (the aldehyde derivative of retinol).
Fat Soluble Vitamins- Vitamin A, Functions

Role of vitamin A in vision

➢ Vitamin A is a component of the visual pigments of rod and cone cells in retina.
- Rod (dim light vision): Rhodopsin (11-cis retinal bound to the protein opsin)
Rhodopsin Cycle
- Cones (bright and color vision): Other retinal-opsin complexes.
➢ Rhodopsin Cycle (visual cycle):
Rhodopsin Light series of photochemical isomerizations
bleaching rhodopsin & release of all-trans-retinal and opsin triggers a nerve
impulse.

For reading
Fat Soluble Vitamins- Vitamin A, Functions-Role of vitamin A in vision

➢ Regeneration of rhodopsin:
- The rhodopsin has to be reconstituted, or the ability
to respond to dim light will be lost completely in a
few seconds at most. This requires isomerization of
all-trans-retinal back to 11-cis retinal.
- This takes place by two side pathways: First, the
all-trans-retinal is re-converted to the 11-cis-retinal
via an isomerase enzyme in retina. Second, all-
trans-retinal after being released from rhodopsin, is
reduced in liver to all-trans-retinol and isomerized to
11-cis retinol that is oxidized to 11-cis retinal which
combines with opsin to form rhodopsin. By the
second pathway additional rhodopsin is
manufactured to adapt to continuously dark
conditions.
Fat Soluble Vitamins- Vitamin A, Vitamin A deficiency
➢ Causes of vitamin A deficiency:
- Decreased intake
- Defective absorption (obstructive jaundice & steatorrhea)
- Reduced synthesis of RBP (liver failure)
- Increased excretion of RBP (kidney failure)
➢ Manifestations of vitamin A deficiency:
Manifestations in the eye:
✓ Night blindness (Nyctalopia)
✓ Xerophthalmia: Dry conjunctiva & cornea.
✓ Keratomalacia (softening of the cornea): If untreated xerophthalmia, bacterial infection , ulceration
& total blindness may occur.
Skin and mucous membrane:
✓ Hyperkeratosis: The skin becomes rough, dry and scaly
✓ Reduced mucous secretion of the respiratory and genitourinary tracts leading to dryness,
susceptibility to bacterial infection & urinary calculi.
Delayed growth of bones and eruption of teeth
Fat Soluble Vitamins- Vitamin k

➢ Chemistry
➢ Dietary sources and requirements
➢ Functions
➢ Deficiency manifestations
Fat Soluble Vitamins- Vitamin k, Chemistry

Chemistry of vitamin K
(Antihemorrhage vitamin):
- The only fat soluble vitamin with a
specific coenzyme function.
- Forms of vitamin K:
(They are naphthoquinone derivatives)
✓ Vit. K1 (phylloquinone): present in
green vegetables.
✓ Vit. K2 (menaquinone): synthesized by
intestinal bacteria.
✓ Vit. K3 (menadione): synthetic, water
soluble and therapeutic form.
Fat Soluble Vitamins- Vitamin k, Dietary sources and requirements

Dietary sources of vitamin K:

- Green leafy vegetables are good vegetable sources.

- Liver and egg yolk are good animal sources.

- Intestinal flora is an important source of vit. K

RDA is 50 – 100 µg/ day For reading

Fat Soluble Vitamins- Vitamin k, Function

Function of vitamin K:

- Vitamin K is a coenzyme in the carboxylation of certain glutamic acid (Glu) residues

present in specific proteins to γ-carboxyglutamate (Gla). These proteins are called Gla

proteins.

Gla proteins: (for example, Blood clotting factors):

✓ The clotting factors II (prothrombin), VII, IX and X are synthesized as inactive

precursors in the liver. Vit. K is coenzyme for their maturation.

✓ Both dicoumarol and warfarin (anticoagulant drugs) antagonize the blood clotting

process through competitive inhibition of vitamin K epoxide reductase (VKOR). This

blocks the recycling of vitamin K and prevents the γ-carboxylation of glutamate

residues in clotting factors.

Fat Soluble Vitamins- Vitamin k, Function
Fat Soluble Vitamins- Vitamin k, Function
Fat Soluble Vitamins- Vitamin k, Deficiency
Fat Soluble Vitamins- Vitamin k, Deficiency
Fat Soluble Vitamins- Vitamin D

➢ Chemistry
➢ Dietary sources and requirements
➢ Functions
➢ Deficiency manifestations
Fat Soluble Vitamins- Vitamin D, Chemistry
Chemistry of vit D (Calciferol, Sunshine vitamin, Antirachitic vitamin)
• Vit D exists in two main biological forms: D2 (ergocalciferol) and D3 (cholecalciferol).

• Cholesterol (in animal tissues) is the precursor to vit D3 while Ergosterol (in plants) is the precursor
to vit D2. Generally, vit D3 comes from animals & vit D2 comes from plants.

• In addition, vit D3 is also synthesized in the human skin.

• Vit D is often called “the sunshine vitamin” as the sun is one of its best sources. In human,
cholesterol can be oxidized in the liver into 7-dehydrocholesterol which can be converted into
vitamin D3 under the skin by ultraviolet B (UVB) rays. Like humans, certain mushrooms and yeast
can make their own vitamin D (vit D2 or ergocalciferol) by irradiating ergosterol upon exposure to
UVB rays.
Fat Soluble Vitamins- Vitamin D, Chemistry
Fat Soluble Vitamins- Vitamin D, chemistry
Fat Soluble Vitamins- Vitamin D, chemistry
• Vit D from the diet or skin synthesis is biologically inactive.
• Enzymatic two hydroxylation reactions in liver and kidney are required for activation;
❑ First hydroxylation reaction takes place in the liver by 25-hydroxylase enzyme.
❑ Second hydroxylation takes place in the kidney by 1-alpha hydroxylase (highly regulated by parathyroid hormone).
• 25-OH vit D is major storage form in the liver & the predominant form in plasma (bound to vit D binding protein).
• 1, 25-diOH-vit D is the metabolically active form, called “Calcitriol”
• Note that: Calcitriol is inactivated by other kidney enzyme, 24-hydroxylase.

Once in the blood, both D2 and D3 bind with vitamin D–binding protein and are carried to the liver, where they are
hydroxylated by 25-hydroxylase to yield 25(OH)D, often called calcidiol. Once they are converted to calcidiol, there
appears to be no difference between the biologic activities of D2 and D3. Calcidiol is then converted in the kidney to
calcitriol by the action of 1-alpha hydroxylase. 25 hydroxylase is unregulated, whereas 1- alpha hydroxylase is highly
regulated and its main regulator is the parathyroid hormone (PTH).
Fat Soluble Vitamins- Vitamin D, Dietary Sources & requirements
Dietary Sources
• Good sources of vit D3 include fish liver oil,
fatty fish and egg yolk. Milk and its products are
poor sources.

• Fungi, such as yeast and certain mushrooms,

produce vit D2 via UVB irradiation of ergosterol.

• Many foods and supplements are fortified

with vit D such as milk and yogurt, fortified
orange juices & fortified ready made cereals.

• Supplementation is required for breast fed

babies.

RDAs are 400 IU/day for growing ages and 800

IU/day for adults. For reading
Fat Soluble Vitamins- Vitamin D, Functions
• Maintenance of normal blood calcium level: Calcitriol has an important role in regulating
body levels of calcium and phosphorus, and in mineralization of bone through;

1- Effect on the intestine: Calcitriol increases the intestinal absorption of calcium & it increases the
phosphate absorption secondary to calcium.

2- Effect on the kidney: Calcitriol minimizes loss of calcium by increasing the reabsorption of calcium
and phosphorus by renal tubules.

3- Effect on bone: Calcitriol provides the proper balance of calcium and phosphorus to support normal
mineralization of bone (deposition of calcium and phosphate into the bone matrix). When serum
calcium levels decrease, Parathyroid hormone (PTH) secretion is stimulated and activates calcitriol
synthesis. Both PTH and calcitriol stimulate calcium mobilization from bones (bone resorption)

• Other functions of calcitriol:

❑ Regulation of the immune System.

❑ Regulation of cell proliferation, differentiation & apoptosis.

❑ Important for secretion of parathyroid & thyroid hormones.

❑ Anti-cancer & Anti-inflammatory

Fat Soluble Vitamins- Vitamin D, Functions
Fat Soluble Vitamins- Vitamin D, Deficiency

Overview for understanding

• Bone mineralization: Deposition of calcium and phosphate into the bone matrix by
special bone cells (osteoblasts) which are hard at work. Bone mineralization process is
dependent on an enzyme called alkaline phosphatase which increases in response to
osteoblast activity.
• The levels of calcium and phosphate in bone and blood are regulated by active vitamin
D and parathyroid hormone (PTH).
• When there's not enough active vitamin D, calcium or phosphate, there's inadequate
mineralization. This means that osteoblasts don’t have enough calcium and phosphate to
deposit into the organic matrix.
• In children, because the growth plates haven’t closed yet, this leads to softening of the
bones, impaired growth of bones, and bone malformations. Whereas, in adults, where
the growth plates have already closed, this only causes weakening and softening of
bones which makes them easier to fracture.
Fat Soluble Vitamins- Vitamin D, Deficiency
Vitamin D deficiency
Causes:
• Inadequate intake
• Insufficient exposure to sun light
• Obstructive jaundice and steatorrhea (↓ absorption)
• Chronic liver and renal diseases (↓ activation)
• Genetic defects of 1- alpha hydroxylase or calcitriol receptors
Manifestations: (rickets in children and osteomalacia in adults)
A- Rickets (↓ mineralization of bone ˃ ˃ soft bone ˃ ˃ bone deformities)
• The head: enlarged, delayed closure of the fontanels, delayed teeth eruption.
• The chest: protruded sternum (pigeon chest) and rosary beads due to enlargement of
costochondral junctions.
• The vertebral column appears with kyphosis or scoliosis.
• The pelvis is contracted.
• The long bones have enlarged osteochondral junctions.
• The lower extremities show bow legs or knock knees.
Fat Soluble Vitamins- Vitamin D, Deficiency

Manifestations:
A- Rickets in children
Fat Soluble Vitamins- Vitamin D, Deficiency
Manifestations: (rickets in children and osteomalacia in adults)

B- Osteomalacia in adults
- Mostly in women especially after repeated pregnancies.
- Demineralization of the bones occurs (bones become softer),
susceptibility to fractures.

( For reading: Osteoporosis is a condition that occurs mostly in women & leads to
loss of bone mass during the aging process due to the loss of calcium and
phosphate. Bones become brittle and prone to fracture. There are three common
causes of osteoporosis, Estrogen Deficiencies in Women, Calcium Deficiencies
(vitamin D is necessary for the proper absorption of calcium), and Inactive
Lifestyle).
Fat Soluble Vitamins- Vitamin E

Vitamin E (Tocopherols)
-Chemistry: There are eight naturally occurring tocopherols, named
α, β, γ, etc.
-Dietary sources: Vegetable oils, nuts, olives, leafy vegetables and
corn are better sources than liver and eggs.
-RDA For reading: is 15 mg/day for adult.
-Function: Antioxidant that prevents non-enzymatic oxidation of
cell components (for example, peroxidation of PUFAs by molecular
oxygen & free radicles)
-Manifestations of Vitamin E deficiency (due to ↑ free radicles)
Hemolytic anemia, largely in premature infants.
 Questions for training

Questions for training will be uploaded on EKB.

 References
• Lecture’s updated pdf & lecture’s notes

• Reference book recommended for more details:

Lippincott's Illustrated Reviews (chapter 28).

 For contact
Please feel free to send me your feedback, your
suggestions and your questions:

• laila.mahdi@med.helwan.edu.eg
• Microsoft Teams (Chat)
• Telegram
Thank you