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Calcium - Tulang

Calcium - Tulang. dr. Susila Sastri M.Biomed Bahagian Biokimia FK-UNAND. extracellular calcium (Ca 2+ : 5 mmol /L and is very rigidly controlled .

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Calcium - Tulang

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  1. 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.

  5. 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%).

  6. Fungsi Ca

  7. 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,

  8. Enzymes and proteins regulated bycalcium or calmodulin.

  9. 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

  10. 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.

  11. 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.

  12. Bone remodeling

  13. 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 (inositoltrisphosphate); 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.

  14. 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

  15. 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.

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

  17. 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.

  18. Calcitriol • steroid hormone calcitriolin 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)

  19. 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.

  20. CLINICAL CORRELATION • Malignancies orhyperparathyroidism : Hypercalcemia : kidney stones • Osteoporotic : Estrogen decrease • Genetic conditions: • familial hypocalciurichypercalcemia • hyperparathyroidism. • Osteomyelitis • osteosarcoma

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