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Applied Biochem > Biochem - Calcium and Phosphate Regulation Pt 1 > Flashcards

Biochem - Calcium and Phosphate Regulation Pt 1 Flashcards

1
Q

Important to maintian extracellular Ca+2 levels because…

A

critical to many cellular functions

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2
Q

Cellular functions that include Ca+2

A

cell divison/adhesion
plasma membrane integrity
2nd messenger signal transduction
muscle contraction
neuronal excitation
blood clotting
skeletal development
Bone, dentin, enamel mineralizaiton

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3
Q

Phospohorus homestasis involved in:

A

membrane composition via phospholipids
intracellular signaling
nucleotide structure
Skeletal development
Bone, dentin, enamel mineralizaiton
Chondrocyte differentiation

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4
Q

Calcium Pools in the body: (3)

A

Bone (99%)
Blood and ECF
Intracellular stores

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5
Q

Bone Calcium

A

99% of total, exists in mineral phase of bone/teeth as HA crystals

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6
Q

HA mineralization of bone is important for

A

weight bearing and mechanical properties of bone

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7
Q

Bone HA serve as a reservoir for

A

calcium to maintain blood homeostasis

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8
Q

Normal range for total serum calcium =

A

8.5-10 mg/dL

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9
Q

What three forms of calcium exist in blood?

A

ionized (biologically active) 45%
Bound to albumin (pH dependent) 45%
Complexed with citrate or phosphate ions 10%

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10
Q

Normal range of IONIZED calcium

A

4.4 - 5.4 mg/dL

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11
Q

Which levels are stable/unstable

A

ionized ca - stable
Total Ca - varies with pH and albumin

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12
Q

Calcium Intake Recommendation for average adult

A

1000 mg

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13
Q

Skeleton stores about ______kg(s) of ca

A

1

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14
Q

Cells maintain ______ intracellular calcium concentration

A

low (0.0001 mM)

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15
Q

Extracellular concentration is much _____ than intracellular

A

higher (by 10,000x)
1 mM

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16
Q

Maintenance of the Intra/Extra concentrations is important because?

A

Ca fluctuation triggers cell functions

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17
Q

Ca gradient across cell membranes achieved by:

A

Ca+2 pumps in membrane

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18
Q

Phosphorous distribution in body (3)

A

1 Free Phosphate ions in solution (inorganic phosphate)
2 HA crystals - 85%
3 other tissues and ECF

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19
Q

Unlike calcium - phosphorus uptake is

A

efficient in the gut

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20
Q

Dietary deficiencies of phosphorous is common/uncommon

A

uncommon

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21
Q

Adult serum Pi concentration

A

2.5 - 4.5 mg/dL

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22
Q

Most extracellular phosphate is free insolution (85%) for what function?

A

Buffer maintains physiological pH

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23
Q

Serum phosphate levels are less tightly regulated than calcium leading to:

A

greater variation in concentrations

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24
Q

Four organ systems involved in Ca+2 and Pi homeostasis

A

Gut, parathyroids, Kidneys, and skeleton

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25
Q

Net zero calcium/phosphate balance -

A

amount of Ca/P ingested = amount excreted

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26
Q

Calcium uptake is a 3 step process: what are the steps?

A

Uptake, Transcellular transport of calcium, and extrusion

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27
Q

Step 1: Calcium uptake

A

calcium comes through apical side of cell - by ion channels of the TRPV6

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28
Q

Step 2: Transcellular Transport of Ca

A

calbindins (calbindin D9K) take calcium from apical to basal side

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29
Q

Step 3: Extrusion

A

on basal surface of cell, by membrane transport proteins - Ca+2 ATPases or Ca & Na exchangers - (Ca+2 ATPase1b) pumps into capillary

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30
Q

During high calcium intake, passive calcium uptake also happens:

A

paracellularly (between epithelial cells)

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31
Q

Phosphate taken up in gut by phosphate transporter located on brush border of ileum:

A

Na+ depedent Pi cotransporter type IIb (NaPi-IIb)

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32
Q

after intestinal absorption of Ca and Pi =

A

filtered by glomerulus in kidney

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33
Q

99% of Ca and 85% of Pi filtered in the kidney is ________

A

reabsorbed

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34
Q

Calcium uptake in renal reabsorption - same as gut with different isoforms of enzymes:

A

Uptake: TRPV5
Transcellular Transport: Calbindin D28K
Extrusion: PMCa1b and NCX1 (same as gut)

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35
Q

Pi uptake in renal absorption - same as gut with with different isoforms whic are:

A

NaPi-IIa
NaPi-IIc

36
Q

Osteoclasts can also transport calcium through the cell by:

A

endocytosis into acidic vesicles followed by exocytosis at cell surface

37
Q

Hormones involved in regulation of calcium/phosphate homeostasis target what?

A

enzymes involed in uptake and resorption

38
Q

Main hormones involved in Ca+2 homeostasis

A

PTH, Calcitrol (1,25 dihydroxyvitamin D3), Calcitonin

39
Q

Main hormones involved in Pi homeostasis

A

PTH, calcitrol, Fibroblast Growth Factor 23 (FGF23)
(dentin matrix protein-1/PHEX)

40
Q

Calcium and Phosphate are always ___________ during bone resorption

A

released together

41
Q

PTH has opposite effects on:

A

Ca and Pi reabsorption in the Kidney

42
Q

Calcitonin is released in response to

A

high serum calcium

43
Q

FGF23 is released in response to

A

high serum phosphate

44
Q

Serum calcium concentrations detected by

A

Calcium Sensing Receptor (CaSR)

45
Q

CaSR is expressed where

A

parathyroid gland

46
Q

Increase serum Ca+2:

A

CaSR receptor signals via PLC/IP3 - lowering PTH secretion

47
Q

Decrease serum Ca+2:

A

CaSR signals via adenylate cyclase/cAMP - increasing PTH secretion

48
Q

PTH is ___ aa long

A

84

49
Q

Ca regulation is confined to the first _____ aa of PTH

A

34

50
Q

Half life of PTH

A

5 minutes

51
Q

PTH receptor

A

PTHR1

52
Q

PTHR1 also binds:

A

parathyroid hormone related peptide (PTHrP)

53
Q

PTH1R is a Class ______ ______ receptor

A

B; G-coupled

54
Q

PTH actions mediated via:

A

activation of adenylate cyclase/cAMP production

55
Q

PTH actions:

A

Increases bone resorption, Increase Ca reabsorption, decreases phosphate reabsorption in kidney

56
Q

Due to phosphate reabsorption being decreased by PTH, in excess it can lead to:

A

phosphaturia

57
Q

In kidney PTH stimulates conversion of:

A

inactive Vitamin D3 (25-hydroxy) to active Vitamin D3 (1, 25 hydroxy)

58
Q

1,25 Vitamin D Actions on Ca+2

A

Induces expression of Calbindins and other components of calcium transport system, resulting in increased: Ca+2 uptake in intestine, reabsorption in kidney tubules, release in to circulation from bone

59
Q

1,25 Vitamin D Actions on Pi

A

Induces expression of phosphate transporters (NaPi-II (a,b,c)) resulting in increased: Pi uptake in intestine reabsorption in kidney tubules, release into circulation from bone

60
Q

Vitamin D overall:

A

increases amount of circulation Ca and Pi

61
Q

Vitamin D3 increase of Ca and Pi leads to a:

A

negative feedback loop for further production of PTH

62
Q

Combined action of PTH and Vitamin D3

A

increase serum Ca/Pi back to normal levels

63
Q

PTH production inibited when

A

Ca+2 returns to normal and inhibition by Vitamin D3 (negative feedback loop)

64
Q

High Ca+2 levels - decrease:

A

PTH secretion

65
Q

Reduced PTH secretion leads to reduced production of:

A

Vitamin D3 in kidney

66
Q

Reduced PTH - leads to reduce of release of Ca and Pi from _____, and reduced _______

A

skeleton; intestinal and renal absorption/reabsorption

67
Q

Effects of PTH are modulated through

A

expression of transporter proteins

68
Q

Calcitonin

A

hormone released by thyroid gland in response to elevated serum calcium

69
Q

Calcitonin opposes:

A

PTH acitons

70
Q

Major effect of calcitonin

A

inhibits osteoclast resorption in bone by retraction of ruffled border

71
Q

Minor effect of calcitonin

A

inhibits renal reabsorption of ca+2 and phosphate

72
Q

Calcitonin thought to play a minor role because of:

A

ineffectiveness of tumors that secrete calcitonin and removal of thyroid has a small effect

73
Q

Main regulators of Pi homeostasis:

A

PTH, Vitamin D3, and FGF23

74
Q

PTH role in Pi homeostasis

A

Increase: phosphate release from bone. Vitamin D3 production in kidney
Decrease: renal reabsorption

75
Q

Vitmain D3 role in Pi homeostasis

A

Increase: phosphate release from bone, renal phosphate reabsorption, and phosphate uptake in gut

76
Q

FGF23

A

32 kDa protein, expression induced in bone when serum phosphate too high

77
Q

When FGF is cleaved into smaller fragments (12 and 20 KDa) what happens to it

A

inactivated

78
Q

FGF23 expression in osteocytes inhibited by two key proteins:

A

Dentin Matrix Protein 1 (DMP1)
Phosphate regulating edopeptidase homolog X-linked (PHEX)

79
Q

Osteocytes:

A

major source of FGF23

80
Q

FGF23 action in kidneys:

A

Decreases reabsorption of Pi (by downregulating expression of phosphate transporters), decreases production of Vitamin D3

81
Q

Overall effect of FGF23

A

lowers serum phosphate

82
Q

main mechanism for rapid regulation of Pi -

A

kidney resorption

83
Q

Type II a & c Na dependent transporters expressed in:

A

proximal tubules of kidney

84
Q

PTH inhibits the __________

A

NaPiII a & c expression

85
Q

Absence of PTH increases

A

phosphate reabsorption

86
Q

FGF23 produced from osteocytes when serum phosphate is high downregulates:

A

NaPiII a & c - reducing reabsorption in kidney

Applied Biochem (13 decks)

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