Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Membrane potential wikipedia , lookup
P-type ATPase wikipedia , lookup
Organ-on-a-chip wikipedia , lookup
SNARE (protein) wikipedia , lookup
Endomembrane system wikipedia , lookup
List of types of proteins wikipedia , lookup
Purinergic signalling wikipedia , lookup
Chemical synapse wikipedia , lookup
Calcium homeostasis Organs in calcium homeostasis • Small intestain • Uptake from dietary • Normal adult diet contains 25mmol, which absorped only 5 mmol /day • Blood/plasma • Coagulation • Transporting with albumin • Main carrier of proteinbound calcium • The plasma total calcium concentration is in the range of 2.2-2.6 mmol/L • The normal ionized calcium is 1.31.5 mmol/L (50-60%) • Protein-bound in albumin (35-50%) • Complexes in organic acids and phosphates (5-10%) Organs in calcium homeostasis • Hormone system • Intracellular secondary messenger • Thyroid gland • Calcitonin • Parathyroid gland • Parathyroid hormone (PTH) • Skeletal system • Storage • 99% of body's total calcium • Calcium makes bones strength • Liver • Cell signaling • Extra cellular fluid • Storage • Transporting to the cells • Cell signaling • Muscle • Contraction • Kidneys • Calcitriol • Remove to urine • In ions 5 mmol/day Calcium homeostasis • Calcium concentration in blood is regulated by calcitonin and PTH activated calcitriol • Calcitriol is released from kidneys. It stimulate cells releasing calcium from bone, increase uptake to gastrointestinal tract and increase reabsorption in renal tubule • Calcitonin is released from thyroid gland and it stimulate calcium deposition in bones and reduce uptake in kidneys when calcium remove to urine Vitamin-D as the regulatory factor of calcium homeostasis • Vitamin-D increases calcium intake from intestine, bones and kidneys • Calcitriol is a vitamin d metabolite that upregulates calcium binding protein expression causing uptake of calcium • Kidneys observe calcium level in blood and produce calcitriol • With the help of renin, calcitriol reabsorbs calcium in the kidneys • Calcium binding proteins can be intracellular and extracellular and they have many functions such as free calcium regulation, calcium transport and signalling (for example calmodulin). Intracellular calcium homeostasis ER Cytosol • High concentration of Ca2+ in rest • IP3 activates calcium release to cytosol through ion-channels • In muscle the sarcoplasmic reticulum releases Ca2+ after synaptic signal • Active pumping of calcium into the ER • Low concentration of Ca2+ • Calcium works as secondary messenger • Calcium can activate some proteins that regulate exocytosis • Intake from ER and extracellular space Calcium pumps and calcium transport • Calcium is actively pumped out of cytosol with Plasma membrane Ca2+ ATPase (PMCA) and Sodium-calcium exchanger (NCX) • PMCA has high affinity but low capacity where as NCX has low affinity but high capacity • This makes PMCA slow and steady when NCX works fast in high Ca2+ concentrations (during signalling where Ca2+ is a secondary messenger) Calcium regulated homeostasis and transport • Calcium has a major role in biomembrane fusion thus regulating many other homeostatic events in the organism • Most of membrane fusions require calcium, such as exocytosis, so the calcium can be released from the vehicle itself or from the ER • Calcium isn't required always and can also inhibit some membrane fusions like pre-golgi-fusion Disorders in calcium metabolism High Deficiency • Hypercalcemia • Milk-alkali syndrome (Burnett's syndrome) • Calcinosis (Calciphylaxix, Calclinosis cutis) • Calcificaltion (Metastatic calcification, Dystrophic calcification) • Familial hypocalciuric hypercalcemia • Excitotoxicity • Hypocalcemia • Osteomalacia • Pseudohypoparathyroidism (Albright's hereditary, osteodystrophy) • Pseudopseudohypoparathyroidism Hypocalcemia Hypercalcemia [𝐶𝑎2+ ]𝐸𝐶𝐹 too high [𝐶𝑎2+ ]𝐸𝐶𝐹 too low Voltage-gated ionchannels opening spontaneously Calcium react with phosphate ions Nerve and muscle cells come hyperactive Involuntary muscle spasms (hypocalcemic tetany) Forming calciumphosphate stones to the blood vessels and to the kidneys Voltage-gated ion channels don´t open so easily Nervous system is depressed