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

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 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

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.

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%).

Fungsi Ca

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,

Enzymes and proteins regulated by calcium or calmodulin.

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.

Bone remodeling

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.

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