Presentation on theme: "Dr. Susila Sastri M.Biomed Bahagian Biokimia FK-UNAND."— Presentation transcript:
dr. Susila Sastri M.Biomed Bahagian Biokimia FK-UNAND
extracellular calcium (Ca 2+ : 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 (Ca 2+ ) 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 (Ca 10 [PO 4 ] 6 [OH] 2 ) Microarchitecture: reservoir of calcium Osteoid: noncalcified organic matrix
Cristal Apatite Complexes of cationic Ca 2+ 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 Ca 2+ : active form (50% of total calcium). protein-bound: bound to negatively charged albumin (40%); Ca 2+ buffers Complexed : citrate and phosphate: (10%).
Bone component: 1–1.5 kg Ca 2+ most of which (about 98%) is located in the mineral substance of bone Signaling substance: Ca 2+ ions act as second messengers in signal transduction pathways: – exocytosis – muscle contraction – cofactors in blood coagulation Enzymes Co –factor Proteins bind Ca 2+ via oxygen ligands,
Enzymes and proteins regulated by calcium or calmodulin.
Factors influencIng calcium homeostasis Parathyroid hormone (PTH) Vitamin D 25-hydroxycholecalciferol (25(OH)D 3 ) is the main liver storage form of vitamin D 1,25(OH) 2 D 3 increases serum concentrations of calcium and phosphate Calcitonin inhibits osteoclastic bone resorption
Calcium effects calcium sensors : biochemical effects of Ca 2+ in the cytoplasm (Ca 2+ binding proteins) : annexins, calmodulin, and troponin C in muscle Calmodulin: Binding of four Ca 2+ ions Ca 2+ ions : regulate the activity of enzymes, ion pumps, and components of the cytoskeleton.
Bone remodeling Mineralization : Deposition of Ca 2+ in bone and Ca 2+ 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, Ca 2+ 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 Ca 2+ 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 Ca 2+ 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 Ca 2+ selective hormones calcitriol, parathyroid hormone, and calcitonin influence this interaction in the bone cells. Parathyroid hormone promotes Ca 2+ 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 Ca 2+ levels through increased Ca 2+ 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 Ca 2+ : taken up per day, about 300 mg of which is resorbed. The same amount is also excreted again. The amounts of Ca 2+ released from bone and deposited in it per day are much smaller. Milk and milk products, especially cheese, are particularly rich in calcium.