Important role in
cellular metabolism
Source of of energy in
cellular reactions
Component of
phospholipids in
membranes
Calcium Homeostasis
It is dependent on
Intestinal
Bone
Renal function
MAINTENANCE OF CALCIUM AND
PHOSPHATE HOMEOSTASIS
Decrease of calcitonin
- hypercalciemia
- hyperphosphatemia
- hypophosphaturia
PARATHYROID GLANDS
Parathyroid hormone - protein
Affects the metabolism
of and
- Promotes moving of 2+
from bones into blood
- Inhibits reabsorption of
in kidneys (decreases the
content of in blood due
to its excretion with
urine)
- Stimulates the absorption
of Ca in the intestine
2 Main regulators of Calcium and
phosphorus:
PARATHYROID HORMONE Vitamin D
1. PTH ( Parathyroid Is a fat soluble steroid
hormone)
84 amino peptide That is present in the diet
Molecular mass if 9.5 and can be synthesized
kilodalton from the skin
no carbohydrate or other
covalently bound molecules
Full biologic activity resides
in the amino terminal third
of the molecule
PTH 1-34 has full biologic
activity while region 25-34
is for receptor binding
PARATHYROID HORMONE
A polypeptide
secreted from the
parathyroid glands
in response to a
decrease in the
plasma
concentration of
ionized calcium
Parathyroid Hormone
Precursor of PTH are:
A. PreproPTH differs
from proPTH by having
additional 25 amino acid
amino terminal
* it is the hydrophobic
end
*at Rough endoplasmic
reticulum
Parathyroid Hormone
Precursor of PTH are:
B. ProPTH differs from
native hormone by
having an amino
terminal highly basic
hexapeptide extension
* it is hydrophobic end
* at PTH golgi apparatus
PTH increases Ca concentration
by:
1. In the presenc e of
permissive amounts of
vitamin D it stimulates
bone
resorptionrelease of
calcium phosphates
2. Enhances intestinal
Calcium and phosphate
absorption promotes
formation of vit D
3. It augments renal
calcium reabsorption
PTH
Regulation of Synthesis
Biosynthesis is regulated by levels of calcium
An acute decrease of Ca results in marked increase of PTH
mRNA increase of PTH synthesis
Effects is at the level of gene transciption, MRNA stability,
mRNA translation
Rate of degradation of PTH is low if low calcium and high if
calcium is high
1, 25 (OH)2D3 receptor complex binds with vitamin D in the
promoter region of PTH gene and inhibits transcription
decreases the production of PTH
PTH synthesis can be enhanced by the size and number of
PTH producing chief cells in cases of prolonged hypocalcemia
Hypofunction
Hyperfunction - hypocalciemia
(Recklinghausens - hyperphosphatemia
disease) - hypophosphaturia
- hypercalciemia - tetanus
- hypophosphatemia
- hyperphosphaturia
- osteoporosis
- Accumulation of
in tissues
Hyperparathyroidism: adenoma
or hyperplasia or ectopic
Hypocalcemia
Regulation of Metabolism and
synthesis of 1,25()H)2-D3
Primary Regulators Secondary
Regulators
Hypocalcemia () Estrogen
PTH() Androgens
Hypophosphatemia() Progesterone
Calcitriol () Insulin
Growth Hormone
Prolactin
Thyroid Hormone
1,25 Vitamin D3
Increases Ca++ uptake from the gut
Increase transcription and translation of Ca++ transport proteins in gut epithelium
Minor roll: also stimulates osteoclasts UV
Increase Ca++ resorption from the bone
Cholesterol precursor 7-dehydrocholesterol
Vitamin D3
25 Vitamin D3
1,25 Vitamin D3