Vitamin D, Calcium homeostasis and biomineralisation Flashcards
Where can vitamin D be made?
In the skin with the help of sunlight
What does public health England recommend to adults and children in regards to vitamin D?
Advises that adults and children over the age of one should consider taking a daily supplement painting 10 micrograms of Vit D
Name the most potentially toxic vitamin
Vitamin D
What can vitamin D cause in high doses?
Nausea
Muscle weakness
In very high doses can cause increased calcium absorption and bone resorption
What effect can increased calcium absorption and bone reparation have on the body
Increased calcium levels in body fluids can leaf to calcification of arteries and organs eventually leading to liver failure
Give some dietary sources of vitamin D
- Egg yolk
- Fish oil
- Some plants
Name the vitamin D precursor
Ergosterol or vitamin D2
Is dietary intake of vitamin D usually enough?
No exposure to sunlight of consumption of supplements with vitamin D are necessary to prevent deficiencies
What is the first stage of vitamin D activation?
Ring cleavage
Name the inactive component of vitamin D found in plants
Ergosterol
What happens to Ergosterol when it is hit with UV?
It becomes ergocalciferol (vitamin D2)
Name the inactive form of vitamin D formed in our liver
7-Dehydrocholesterol
What happens to 7-Dehydrocholesterol when it is hit with UV
Cholecalciferol
Vitamin D3
Name the stages involved in vitamin D botsynthesis/activations
- Ring cleavage
2. Double hydroxylation
How is Cholecalciferol
(Vitamin D3) activated
It undergoes double hydroxylation
Go through the steps of the double hydroxylation of Cholecalciferol
(Vitamin D3)
- Cholecalciferol
(Vitamin D3) is inactive in the liver - First hydroxylation occurs by enzymes in the liver at position 25
- Second hydroxylation occurs in the kidneys at position 1
Where does the double hydroxylation of vitamin D occur?
First hydroxylation occurs in the liver
Second hydroxylation occurs in the kidneys
Name the 2 precursors of vitamin D
- Ergosterol (provitamin D2)
2. 7- Dehydrocholesterol (provitamin D3)
Name the 3 intermediates of vitamin D
- Ergocalciferol (vitamin D2)
- Cholecalciferol (Vitamin D3)
- 25-Hydroxycholoecalciferol
Name the activated form of vitamin D3
Calcitriol or 1,25- Dihydroxyvitamin D3
Is vitamin D hydrophobic or hydrophilic?
Hydrophobic
How is vitamin D transported?
It is transported in blood bound vitamin D binding protein (DBP)
What is the half life of 25- hydroxycholecalciferol
several weeks
What is the half life of 1,25 dihydroxycholecalciferol
A few hours
What can imbalances in calcium serum levels lead to?
Can lead to hypercalcaemia and hypocalcaemia
What is the normal range of calcium serum levels a person should be within?
2.2-2.7mmol/L
Which hormone is released when calcium levels are low?
The parathyroid hormone (PTH)
What does the parathyroid hormone (PTH) do?
- Enhances bone resorption and increases efflux of Ca2+ from bone
- Also decreases the loss of calcium from Turin
What response does the body have when it detects low calcium levels in the blood?
- The parathyroid hormone is released (PTH)
- This hormone enhances bone resorption and increases efflux of Ca2+ from bone
- Also decreases the loss of calcium from urine
Which form of vitamin D is involved in controlling calcium serum levels?
Vitamin D3
How does vitamin D3 respond when low calcium levels are detected in the blood
It enhances absorption of calcium from the intestine
Where is vitamin D3 found?
In the kidneys
Name the glands involved in controlling serum calcium levels
- Thyroid glands
2. Parathyroid glands
What is the parathyroid hormone (PTH) secreted by?
Parathyroid glands
Does the parathyroid hormone (PTH) increase or decrease serum calcium?
Increases it
What does parathyroid hormone (PTH) activate indirectly?
Osteoclastogenesis
What effect does the parathyroid hormone (PTH) have on RANKL and OPG
Increases RANKL
Decreases OPG
What is calcitonin produced by?
Produced by the parafollicular cells in the thyroid
What effect does calcitonin have on parathyroid hormone (PTH)
It has an antagonistic effect
Does calcitonin increase or decrease serum calcium?
Decreases
What does calcitonin do?
It decreases serum Ca2+ by inhibiting osteoclasts
The parathyroid hormone (PTH) hormone stimulates the production of C__________
Calcitriol
What is calcitriol
1,25 Dihydroxy vitamin D3
What is the production of calcitriol stimulated by?
The parathyroid hormone (PTH)
What is calcitriol do?
It increases calcium absorption in the intestines
How does calcitriol increase calcium absorption in the intestine?
Vitamin D responsive elements (VDRE) directly regulate gene expression eg osteocalcin
Name the enzyme that catalyses the hydroxylation of C25 in the liver
25 hydroxylase enzyme
Does the 25 hydroxylase enzyme need to be activated?
No it is always active and ready to hydroxylate any cholecalciferol and ergocalciferol
What can the 25-hydroxylase enzyme be inhibited by?
25- hydroxyvitamin D3
Talk through when the Parathyroid
Hormone
(PTH) is released and what effect it has on the kidneys
- Low serum calcium levels are detected
- The Parathyroid
Hormone is released by the parathyroid gland - Hormone travels to kidneys and activated the 1-hydroxylase enzyme
- This enzyme then aids het reaction of 25-hydroxyvitamin D3 into 1,25-hydroxyvitamin D3
What are al steroid hormone the in body derived from?
Cholesterol
Where are steroid hormones secreted from?
Steroid glands
Are steroid hydrophobic or hydrophilic?
Hydrophobic (lipophilic)
What do steroid do?
They directly regulate the expression of certain responsive geneses in conjunction with additional factor
Name some common steroids found in the body
- Cortisol
- Testosterone
- Vitamin D3
- Retinoic acid
How are steroid hormones activated and what affect does their activation have?
Steroid receptors bind to cognate steroid hormones and become activated
This then activates transcription of target genes
What is the human osteroclacin gene responsible for?
Biomineralisation and bone matrix synthesis
What is human Osteocalcin produced by?
Osteoblasts and odontoblasts
What does human Osteocalcin do?
- Binds hydroxyapatite and calcium
- Modulated mineralised matrix mechanical properties
- It is a marker of matrix mineralising cells
What can a deficiency in human Osteocalcin lead to?
Osteopetrosis
What percentage of the bone matrix is composed of human Osteocalcin?
2%
How much vitamin D do adults require daily?
5-10 micrograms (200-400 iu)
State the normal serum levels of vitamin D in an adult
25-80ng/ml
What can deficiency of vitamin D3 lead to in children?
Skeletal mineral deficiencies such as rickets and osteomalacia
What can deficiency of vitamin D3 lead to in children?
Skeletal mineral deficiencies such as kidney insufficiency and liver cirrhosis
What affect can vitamin D3 deficiency has orally?
- Can increase a patients risk of developing dental caries and periodontal disease
- Can lead to enamel and dentine hypoplasia or incomplete/delated development
- Can have effects on the alveolar bone
What is the significance of vitamin D3 in the mouth?
It is necessary for the mineralisation of oral hard tissues including bone an d teeth
What does the 25 hydroxylase enzyme do?
Ut catalyses the hydroxylation of C25 in the liver (Vitamin D activation)