lecture 19: calcium

Question 1

calcium as a second messenger

Answer 1

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

Question 2

phospholipase C in calcium release

Answer 2

stimulation leads to hydrolysis of PTI > DAG + IP3
increased cytosolic IP3 > release of intracellular Ca2+ stores

Question 3

removal of Ca2+ stimulus

Answer 3

ca binding proteins to buffer free Ca2+

compartmentalization: uptake into cell organelles

Ca2+ pumps

Question 4

phospholipase A2

Answer 4

enzyme in lipid digestion that requires Ca2+ binding to hold phosphate group of phospholipid substrate

Question 5

blood clotting and Ca2+

Answer 5

required for activation of prothrombin, factor X, protein S

Question 6

calpains

Answer 6

Ca2+ dependent proteases
remodelling of membrane attachments, signal transduction, apoptosis

Question 7

bone tissue

Answer 7

reservoir for minerals
contains 99% of body’s calcium

Question 8

hydroxyapatite

Answer 8

calcium phosphate compound that calcium is mainly found as

Question 9

Matrix Gla protein (MGP)

Answer 9

produced by smooth muscle
binds Ca2+ to inhibit vascular calcification

Question 10

parathyroid hormone (PTH)

Answer 10

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

Question 11

annexins

Answer 11

bind negatively charged phospholipids in a Ca2+ dependent manner, act as membrane scaffold proteins

Question 12

bone resorption

Answer 12

removal of mineral from bone

Question 13

most important function of Ca2+

Answer 13

muscle contraction (heart pumping)

Question 14

osteonectin

Answer 14

calcium binding protein, promotes osteoblast proliferation and survival, maintenance of bone mass

Question 15

calcitonin

Answer 15

increases in proportion to Ca2+
acts in opposition to PTH, lowers blood calcium levels, inhibits osteoclast activity

Question 16

vitamin D in increasing calcium levels

Answer 16

1,25(OH)2D and VDR heterodimer can increase expression of CaT1 and calbindin-D for increased calcium absorption

Question 17

FGF

Answer 17

lowers blood phosphate levels, reduces production of 1,25 vitamin D

Question 18

intestinal absorption of calcium

Answer 18

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.

Question 19

2 pathways for calcium absorption in intenstine

Answer 19

1) transcellular, energy dependent pathway under hormonal regulation by vitamin D
2) paracellular, energy independent

Question 20

transcellular Ca2+ transport

Answer 20

regulated by 1,25(OH)2D, CaT1, calbindin D, basolateral Ca2+ ATPase

Question 21

intestinal absorption of phosphate

Answer 21

influenced by vitamin D status

Question 22

osteoclasts vs osteoblasts

Answer 22

osteoclasts: bone resorption - rate of bone breakdown, releases calcium in blood
osteoblasts: bone formation - rate of bone deposition

Question 23

RANKL

Answer 23

ligand produced in osteoblasts, binds on osteoclasts to stimulate differentiation, activation, survival of osteoclasts

increase bone resorption

Question 24

Describe how low plasma concentrations of calcium lead to increased activation of Vitamin D to the hormonal form.

Answer 24

low plasma Ca detected by CaSRs > increase in PTH secretion > increases 1a-hydroxylase activity > converts 25OHD to 1,25 OH2D

Question 25

What other biomarkers could you use to determine whether Ca2+ is being used as a second messenger? Would this (these) marker(s) be upstream or downstream of intracellular Ca2+ release?

Answer 25

Calmodulin: activated by calcium, downstream
IP3: release of intracellular Ca, upstream