lecture 19: calcium Flashcards
calcium as a second messenger
almost all calcium within cells is bound within organelles
free calcium in cytosol significantly lower than extracellular space
changes in intracellular Ca2+ conc in response to cell-surface binding
phospholipase C in calcium release
stimulation leads to hydrolysis of PTI > DAG + IP3
increased cytosolic IP3 > release of intracellular Ca2+ stores
removal of Ca2+ stimulus
ca binding proteins to buffer free Ca2+
compartmentalization: uptake into cell organelles
Ca2+ pumps
phospholipase A2
enzyme in lipid digestion that requires Ca2+ binding to hold phosphate group of phospholipid substrate
blood clotting and Ca2+
required for activation of prothrombin, factor X, protein S
calpains
Ca2+ dependent proteases
remodelling of membrane attachments, signal transduction, apoptosis
bone tissue
reservoir for minerals
contains 99% of body’s calcium
hydroxyapatite
calcium phosphate compound that calcium is mainly found as
Matrix Gla protein (MGP)
produced by smooth muscle
binds Ca2+ to inhibit vascular calcification
parathyroid hormone (PTH)
contains calcium sensing receptor (CaSR) to sense low plasma calcium levels
bone and kidney are primary target organs
stimulates cAMP production
increased PTH concentrations > increased rate of renal Ca2+ reabsorption and decrease phosphate reabsorption
annexins
bind negatively charged phospholipids in a Ca2+ dependent manner, act as membrane scaffold proteins
bone resorption
removal of mineral from bone
most important function of Ca2+
muscle contraction (heart pumping)
osteonectin
calcium binding protein, promotes osteoblast proliferation and survival, maintenance of bone mass
calcitonin
increases in proportion to Ca2+
acts in opposition to PTH, lowers blood calcium levels, inhibits osteoclast activity
vitamin D in increasing calcium levels
1,25(OH)2D and VDR heterodimer can increase expression of CaT1 and calbindin-D for increased calcium absorption
FGF
lowers blood phosphate levels, reduces production of 1,25 vitamin D
intestinal absorption of calcium
Ca absorption efficiency varies w calcium status
Though calcium absorption efficiency decreases with increasing intake, the total calcium absorbed increases with the total calcium load.
2 pathways for calcium absorption in intenstine
1) transcellular, energy dependent pathway under hormonal regulation by vitamin D
2) paracellular, energy independent
transcellular Ca2+ transport
regulated by 1,25(OH)2D, CaT1, calbindin D, basolateral Ca2+ ATPase
intestinal absorption of phosphate
influenced by vitamin D status
osteoclasts vs osteoblasts
osteoclasts: bone resorption - rate of bone breakdown, releases calcium in blood
osteoblasts: bone formation - rate of bone deposition
RANKL
ligand produced in osteoblasts, binds on osteoclasts to stimulate differentiation, activation, survival of osteoclasts
increase bone resorption
Describe how low plasma concentrations of calcium lead to increased activation of Vitamin D to the hormonal form.
low plasma Ca detected by CaSRs > increase in PTH secretion > increases 1a-hydroxylase activity > converts 25OHD to 1,25 OH2D
