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• 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.
Struktur tulangBone : connective tissue, substantial
metabolic activity. type 1 collagen: the major protein (90%)calcium-rich crystals : hydroxyapatite
(Ca10[PO4]6[OH]2)Microarchitecture: reservoir of calciumOsteoid: noncalcified organic matrix
Cristal ApatiteComplexes of cationic Ca2+ matched
by HPO4 2–, CO32–, OH–, or F– as anions. carbonate apatite Ca10(PO4)6CO3hydroxyapatite Ca10(PO4)6 (OH)2fluoroapatite Ca10(PO4)6F2
In adults, more than 1 kg calcium is stored in bone.
Calcium circulationionized Ca2+: active form (50% of total calcium).
protein-bound: bound to negatively charged albumin (40%); Ca2+ buffers
Complexed : citrate and phosphate: (10%).
• 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,
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
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.
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.
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.
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
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.
Maintaining bone mass - the bone remodeling cycle.
Resorption and formation of bone by osteoclasts and osteoblasts is coupled
• 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.
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)
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.