VITAMIN - D
Rudraditya Tushar
Roll no. 88 Roll no. 118
OBJECTIVES
Chemistry and Structure of Vitamin D
Synthesis of Vitamin D
Activation of Vitamin D
Biochemical effects of Vitamin D
Disorders related to Vitamin D (Deficiency and Toxicity)
VITAMIN D (CHOLECALCIFEROL)
• Fat Soluble Vitamin
• Atypical Vitamin
• “Sunshine Vitamin”
This Photo by Unknown Author is licensed under CC BY
Two Forms
Aspect Vitamin D2 (Ergocalciferol) Vitamin D3 (Cholecalciferol)
Source Synthesized by plants Synthesized in the skin of
humans and animals
(UV radiation exposure) (UV radiation exposure)
Found in fortified foods Found in some animal-based
(e.g., cereals, milk, foods (e.g., fatty fish,
orange juice) egg yolks, liver)
Biological Activity Less potent, less bioavailable More potent, more bioavailable
than D3 than D2
Metabolism Similar metabolic pathways Similar metabolic pathways
in liver and kidneys in liver and kidneys
Half-Life Shorter half-life Longer half-life
Availability Less readily available More readily available
Clinical Use Used to treat/prevent Used to treat/prevent
vitamin D deficiency, vitamin D deficiency,
osteoporosis osteoporosis
Sources of Vitamin D
ARTIFICIAL NATURAL
Fish liver oil
Supplements Cod liver oil
Salmon fish
Egg Yolk
Adequate exposure to sunlight
Supplementation with Vit D3 is better than with
D2, as D3 has longer half life.
RDA (Recommended Dietery Allowance)
of Vitamin D
Children 400 IU/day (10ug)
Adults 200 IU/day
Pregnancy,Lactation 400 IU/day
Above age 60 600 IU/day
https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/
Synthesis of Vitamin D2 & D3
Activation of Vitamin D
UV-B rays
7-Dehydrocholesterol Cholecalciferol
D- binding protein
( Provitamin D3 )
7-Dehydrocholesterol (stored in liver)
25-hydroxy vitamin D3
25-Hydroxylase or
Cholecalciferol 25-hydroxycholecalciferol
Co-factors
• Mg++ or
• NADPH Calcifediol
• O2 or
Calcidiol
Hypocalcemia
Parathyroid Hormone
1-α-Hydroxylase 25-hydroxycholecalciferol
1,25-Dihydroxycholecalciferol
or D- binding protein
Calcitriol Co-factors
• Mg++
• NADPH
• O2
Calcitriol is the most active form of vitamin D3
Feedback Mechanism is present
Too much Calfediol 25-Hydroxylase
Too much calcitriol 1-α-Hydroxylase
Calcitriol at high concentration:
ACTIVE FORM INACTIVE FORM
1,25-Dihydroxycholecalciferol 24,25-Dihydroxycholecalciferol
1,24,25-trihydroxycholecalciferol
Calcitriol as Hormone
The active form of vitamin D ( calcitriol ) act as Hormone
Vitamin D is traditionally categorized as a vitamin due to its essentiality in the diet
It’s functions, synthesis, distribution, and regulatory mechanisms align closely with those of
hormones
Like hormones it is
Synthesized in body
Released in circulation
Has distant site of action ( kidney, intestine, bones )
Bind to nuclear receptors like steroid hormones
Subjected to feedback regulation
Biochemical Effect of Vitamin D
Increase intestinal absorption of Ca and phosphate ions
Mineralization of bones
Increase reabsorption of Ca and Phosphate ions from renal tubules
Immune system modulator
Insulin secretion
Blood pressure regulation
Effect of Vitamin D on Intestine
Increase calcium
absorption with help of
protein calbindin
Increase phosphate
absorption
Effect of Vitamin D on Kidney
• Increase calcium and
phosphate reabsorption
Ca++
PO4--
Effect of Vitamin D on Bones
Increase bone mineralization
PO4--
Ca++
If, there is low calcium level
Vitamin D increases osteoclastic
activity.
Regulation of calcium and phosphate level
Ca absorption
Mineralization of bones Ca reabsorption
PO4- reabsorption PO4- absorption
Like other hormones, vitamin D -
feedback regulation.
Parathyroid hormone Serum Ca++ Serum PO4-- Calcitriol
(Directly increases the formation of calcitriol and thus serum ca and phosphate levels)
How do we measure vitamin D
levels in Labs?
By assessing the concentration of 25-hydroxyvitamin D (25(OH)D) in
the blood
It reflects both dietary intake and synthesis from sunlight.
PROCEDURE
1. Blood Sample Collection
2. Centrifugation (to separate the serum)
3. Analysis using various techniques
4. Reporting Results
Techniques for analysing
• High-performance liquid chromatography (HPLC)
• Liquid chromatography-tandem mass spectrometry (LC-MS/MS)
• Immunoassays
LC-MS/MS is considered the gold standard method for measuring
25(OH)D levels due to its high specificity and sensitivity.
Disorders Related to Vitamin D
Vitamin-D Deficiency
The deficiency diseases are Rickets in children and Osteomalacia in adults
The optimal concentration of 25-hydroxy D3 is > 30 ng/mL
20–29 ng/mL is considered insufficient
10–19 ng/mL is deficient
below 10 ng/mL indicates severe deficiency
Deficiency is more common in obese people
(because vitamin D is stored in adipose tissue, and not released for utilization)
Vit D deficiency associated with
-poor bone health
-low calcium concentration
-higher systolic blood pressure
-lower HDL cholesterol values
Causes of Vitamin-D deficiency
Deficiency of vitamin D can occur in people who are not exposed to sunlight
properly
Inhabitants of northern latitudes, in winter months, in people who are
bedridden for long periods
Nutritional deficiency
Malabsorption of vitamin
Abnormality of vitamin D activation
Rickets
Rickets is seen in children
insufficient mineralization of bone
Bones become soft and pliable
classical features of rickets are bone deformities.
.
Clinical manifestations include bow legs, knock knee, rickety rosary,
bossing of frontal bones, and pigeon chest
Enlargement of the epiphysis at the lower end of ribs and costochondral
junction leads to beading of ribs or rickety rosary.
Harrison’s sulcus is a transverse depression passing outwards from the
costal cartilage to axilla. This is due to the indentation of lower ribs at
the site of the attachment of diaphragm.
Knock Knee Bow Leg
Rickety Rosary
•
Pegion Chest Bossing of Frontal bone
Harrison’s Sulcus
Types of Rickets
The classical vitamin D deficiency rickets (can be cured by giving vitamin D in the diet)
The Hypophosphatemic rickets mainly result from defective renal tubular reabsorption of phosphate.
• (Supplementation of vitamin D along with phosphate is found to be useful)
Vitamin D resistant rickets is found to be associated with Fanconi syndrome, where the renal tubular
• reabsorption of bicarbonate, phosphate, glucose, and amino acids are also deficient.
Renal rickets: In kidney diseases, even if vitamin D is available, calcitriol is not synthesized.
Osteomalacia
“osteon” = bone; and “malakia” = softness
Bones are softened due to insufficient mineralization and increased osteoporosis
Patients are more prone to get fractures.
lower serum calcium, and a low serum phosphate
vitamin D deficiency never produces severe Hypocalcemia
Serum alkaline phosphatase, bone iso-enzyme, is markedly increased.
Hypervitaminosis D
Doses above 10,000 units per day for long periods may cause toxicity.
Symptoms include weakness, polyuria, intense thirst, difficulty in
speaking, hypertension and weight loss.
Hypercalcemia leads to calcification of soft tissues, (metastatic
calcification, otherwise called calcinosis), especially in vascular and
renal tissues.
vitamin D is toxic in higher doses, excessive exposure to sunlight does
not result in vitamin D toxicity, because excess D3 is destroyed by
sunlight itself
MCQs
Out of vitamin D2 and D3, which
vitamin is preferred as a suppliment
and why?
a) Vitamin D2, longer half life
b) Vitamin D3, shorter half life
c) Vitamin D2, shorter half life
d) Vitamin D3, longer half life
What is the effect of Calcitriol on
intestine?
a) increase calcium and phosphate absorption
b) decrease calcium and phosphate absorption
c) increase calcium absorption but decrease phosphate absorption
d) decrease calcium absorption but increase phosphate absorption
Soft, weak and bendable bone in
children describe a disease called?
a) Rickets
b) progeria
c) osteoporosis
d) all of above
What are signs and symptoms of
vitamin D deficiency?
a) Fatigue or tiredness
b) General aches and pains
c) frequently infections
d) all of above
Bibliography
Lippincott's Illustrated Reviews – Biochemistry South Asian Edition
Harper's Illustrated Biochemistry, 32nd Edition
https://ods.od.nih.gov/ ( National Institute of Health )
Thankyou