1. dr. Susila Sastri M.Biomed Bahagian Biokimia FK-UNAND
Calcium - Tulang
dr. Susila Sastri M.Biomed
Bahagian Biokimia
FK-UNAND

2. extracellular calcium (Ca2+ : 5 mmol/L and is very rigidly controlled.
amounts of calcium: associated with intracellular organelles such as mitochondria and the endoplasmic reticulum, the intracellular concentration of free or ionized calcium (Ca2+ ) is very low: 0.05–10 mmol/L.

3. Struktur tulang
Bone : connective tissue, substantial metabolic activity.
type 1 collagen: the major protein (90%)
calcium-rich crystals : hydroxyapatite (Ca10[PO4]6[OH]2)
Microarchitecture: reservoir of calcium
Osteoid: noncalcified organic matrix

4. Cristal Apatite
Complexes of cationic Ca2+ matched by HPO4 2–, CO32–, OH–, or F– as anions.
carbonate apatite Ca10(PO4)6CO3
hydroxyapatite Ca10(PO4)6 (OH)2
fluoroapatite Ca10(PO4)6F2
In adults, more than 1 kg calcium is stored in bone.

6. Calcium circulation ionized Ca2+: active form (50% of total calcium).
protein-bound: bound to negatively charged albumin (40%); Ca2+ buffers
Complexed : citrate and phosphate: (10%).

8. Fungsi Ca

9. Bone component: 1–1.5 kg Ca2+ most of which (about 98%) is located in the mineral substance of bone
Signaling substance: Ca2+ ions act as second messengers in signal transduction pathways:
exocytosis
muscle contraction
cofactors in blood coagulation
Enzymes Co –factor
Proteins bind Ca2+ via oxygen ligands,

10. Enzymes and proteins regulated by calcium or calmodulin.

11. Factors influencIng calcium homeostasis
Parathyroid hormone (PTH)
Vitamin D
25-hydroxycholecalciferol (25(OH)D3) is the main liver storage form of vitamin D
1,25(OH)2D3 increases serum concentrations of calcium and phosphate
Calcitonin inhibits osteoclastic bone resorption

12. Calcium effects
calcium sensors : biochemical effects of Ca2+ in the cytoplasm (Ca2+ binding proteins) : annexins, calmodulin, and troponin C in muscle
Calmodulin: Binding of four Ca2+ ions
Ca2+ ions : regulate the activity of enzymes, ion pumps, and components of the cytoskeleton.

14. Bone remodeling
Mineralization : Deposition of Ca2+ in bone and Ca2+ mobilization from bone are regulated by at least 15 hormones and hormone like signaling substances.
These mainly influence the maturation and activity of bone cells.
Osteoblasts : deposit collagen, Ca2+ and phosphate, and thereby create new bone matter
Osteoclasts : secrete H+ ions and collagenases that locally dissolve bone (bone remodeling).
Osteoblasts and osteoclasts mutually activate each other by releasing cytokines and growth factors.
bone formation and bone breakdown : balance.

15. Bone remodeling

16. Calcitonin
Calcitonin: A polypeptide hormone (32-amino acid) residues that is synthesized in the parafollicular cells (C cells) of the thyroid gland.
Calcitonin is secreted in response to elevated blood Ca2+ levels.
IP3: Inositol 1,4,5-trisphosphate (inositol trisphosphate); a second messenger
IP3 bind to receptors on the endoplasmic reticulum (ER) to cause the rapid efflux of Ca2+ from the ER into the cytoplasm.

17. Parathyroid hormone
PTH: 84-amino acid polypeptide hormone that is synthesized in the parathyroid gland and is secreted in response to low blood Ca2+ levels.
PTH: increase the Ca2+ concentration in the blood by stimulating osteoclast formation and activity, thus releasing bone calcium and phosphate into the blood

18. Vitamin D
Vitamin D3: a secosteroid formed by the action of UV light on 7-dehydrocholesterol.
The active form of vitamin D: hormone 1,25-dihydroxycholecalciferol (calcitriol), formed in the kidney in response to elevated PTH levels.
It binds to nuclear receptors in intestine, bone, and kidney to activate the expression of calcium-binding proteins.

19. Maintaining bone mass - the bone remodeling cycle.
Resorption and formation of bone by osteoclasts and osteoblasts is coupled

20. The Ca2+ selective hormones calcitriol, parathyroid hormone, and calcitonin influence this interaction in the bone cells.
Parathyroid hormone promotes Ca2+ release by promoting the release of cytokines by osteoblasts.
Cytokines: stimulate the development of mature osteoclasts from precursor cells
Calcitonin inhibits this process. At the same time, it promotes the development of osteoblasts
Osteoporosis: women following the menopause (reduction in estrogen levels)
Estrogens normally: inhibit the stimulation of osteoclast differentiation by osteoblasts. If the effects of estrogen decline, the osteoclasts predominate and excess bone removal occurs.

21. Calcitriol steroid hormone calcitriol in bone are complex.
promotes bone formation by stimulating osteoblast differentiation, important in small children, in whom calcitriol deficiency can lead to mineralization disturbances
increases blood Ca2+ levels through increased Ca2+ mobilization from bone.
An overdose of vitamin D (cholecalciferol), the precursor of calcitriol, can therefore have unfavorable effects on the skeleton similar to those of vitamin deficiency (hypervitaminosis)

22. Calcium homeostasis Ca2+metabolism: balanced in healthy adults.
1 g Ca2+ : taken up per day, about 300 mg of which is resorbed.
The same amount is also excreted again.
The amounts of Ca2+ released from bone and deposited in it per day are much smaller.
Milk and milk products, especially cheese, are particularly rich in calcium.

24. CLINICAL CORRELATION
Malignancies or hyperparathyroidism : Hypercalcemia : kidney stones
Osteoporotic : Estrogen decrease
Genetic conditions:
familial hypocalciuric hypercalcemia
hyperparathyroidism.
Osteomyelitis
osteosarcoma