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BIOL 432 > Vitamin D and Calcium > Flashcards

Vitamin D and Calcium Flashcards

1
Q

3 sites of extracellular fluid interface for calcium exchange

A
  • the intestine
  • bone
  • renal tubule (kidney)
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2
Q

extracellular fluid interface for calcium exchange is mainly regulated by…

A

vitamin D and parathyroid hormone, but also calcitonin

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3
Q

only ___ of total body Ca is in extracellular fluid - mostly in ___

A

1%, bone

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4
Q

what is the regulatory role of calcium in cellular function?

A

excitation/contraction in the heart muscles, synapse function, platelet aggregation, coagulation, and hormone secretion by exocytosis

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5
Q

why is tight regulation of intracellular calcium necessary?

A

bcuz there is typically a 10,000 fold lower concentration of calcium inside the cell compared to outside. this regulation is maintained by ATP-dependent calcium pumps and the Na+/Ca2+ exchanger

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6
Q

how do cells allow calcium back inside after its expulsion?

A

by rapid flow through calcium channels (receptor or voltage controlled) or by releasing internal stores from the endoplasmic reticulum or mito, often through IP3 signaling

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7
Q

what are some processes that rely on calcium as a second messenger?

A

cell division, muscle contraction, cell movement, membrane trafficking, and secretion

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8
Q

what are the consequences of parathyroid gland removal?

A

leads to severe hypocalcemia, tetany (involuntary muscle contraction) and potentially death due to role of parathy hormone in calcium regulation

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9
Q

how does space flight-induced loss of gravity affect calcitonin production and bone health?

A

induces loss of parafollicular cells, resulting in decreased calcitonin production and bone loss.

  • calcitonin can be used to treat lytic paget’s dz, hypercalcemia and osteoporosis
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10
Q

what are implications of vitamin D receptors in various tissues beyond bone, kidney and intestine?

A

are present in immune, testis and breast cells, implications in cancer prevention. also crucial for hormone synthesis and secretion, and regulating genes via a nuclear receptor

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11
Q

mature osteoclast

A

bone resorption cell moves to bone surface and secretes acid and enzymes to break down
bone in bone remodeling cycle; inhibited by calcitonin; mature cell does not divide; has receptor for calcitonin but
NOT for vit D or PTH

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12
Q

osteoblast

A

bone forming cell;
secretes bone matrix; has
receptors for PTH and Vit. D

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13
Q

macrophages

A

are “mops” of immune system, but also critical role in bone remodeling

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14
Q

how much of the adult skeleton is replaced approx every 10 years?

A

about 10% is remodeled if physical or biochemical signals prompt it

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15
Q

what are the steps involved in bone remodeling?

A

A) Resting bone surface
B) Osteoclasts dig a hole by releasing acid and enzymes
C) Macrophages clean up the area
D) Osteoblasts are recruited to the site
E) Osteoblasts secrete bone matrix
F-G) Calcification and Mineralization occur, resulting in the formation of crystals of hydroxyapatite and collagen.

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16
Q

how long does the bone remodeling process take and what are the conseqences of an imbalanced remodeling cycle?

A

approx 6 months, bone loss may occur over time - due to low calcium, medications, fractures, hormone imbalances or aging

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17
Q

vitamin D made in…

A

combo of skin, liver and kidney

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18
Q

calcitonin made in…

A

parafollicular cells in thyroid gland (C cells)

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19
Q

parathyroid hormone made in..

A

parathyroid cells of parathyroid gland

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20
Q

what is the role of vitamin D in bone and teeth formation?

A

essential for formation by maintaining blood levels of Ca ions and phosphate ions

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21
Q

besides its role in bone health, what other important effects does vitamin D have?

A

cell differentiation and development

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22
Q

what are the different forms of vitamin D?

A

fat soluble vitamins - D1, D2, D3. calcitriol is the active vitamin D hormone - one of forms of D3

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23
Q

why is vitamin D considered more than just a vitamin?

A

bcuz we primarily produce it (90%) in skin when exposed to UV light from a metabolite of cholesterol. obtain 10% from diet

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24
Q

what is calcitriol?

A

active form of vitamin D hormone, one of forms of vitamin D3

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25
Q

how does sun exposure affect vitamin D synthesis?

A

exposure of reasonable intensity for ten to fifteen minutes at least two times per week to the face, arms, hands, or back without sunscreen can promote Vitamin D synthesis in the skin. However, factors such as season, geographic latitude, time of day, cloud cover, smog, clothing, and sunscreen usage can influence UV ray exposure and Vitamin D synthesis.

26
Q

why is sunlight exposure during certain months insufficient for vitamin D synthesis in northern latitudes?

A

from nov-feb is insufficient due to lower sun angles and reduced UVB.

27
Q

why are vitamin D drops recommended for babies?

A

they may not receive sufficient sunlgiht exposure

  • can be toxic at high doses especially in ppl with kidney problems or hypercalcemia
28
Q

what wavelength require for vit d?

A

295nm of UVB (cannot make indoors)

29
Q

explain vitamin d structure

A

related to steroids and not a vitamin in this context
because uses same type of high affinity nuclear receptor to affect
transcription as steroids, and levels regulated (as compared to a
vitamin that is typically from diet and is a cofactor for some protein
or enzyme to assist in its function)

30
Q

explain vitamin d receptors

A

Vit D receptors in bone, kidney and gut, but also
others like immune cells, testis and breast; important implications
for cancer (vitamin D signals antiproliferation)

31
Q

explain vitamin D regulation

A

concentration vit D is upregulated by low phosphate,
low calcium ions, low vit D and high parathyroid hormone. If high
vit D, feedback inhibits own vit D receptor transcription and
upregulates hydroxylase that will break down vit D. Note that vit D
is NOT a protein so does not have decreased expression but
rather faster breakdown and reduced receptor to receive signal

32
Q

how are vitamin D3 and D2 transported in the body?

A

by specific vitamin D transport proteins to the liver, where the cytochrome P450 oxidase enzyme acts on them

33
Q

where can vitamin D precursor be stored until needed? what controls its activation?

A

in liver and fat until needed. main control for its activation occurs at kidneys, where low levels of phosphate, calcium ions and vitamon D, w high levels of parathyroid hormone, favor the production of 1,25-dihydroxyvitamin D (calcitriol). This conversion is catalyzed by cytochrome P450 enzymes and is the rate-limiting step for synthesis.

34
Q

what enzyme involved in deactivating vitamin D in liver and kidney?

A

hydroxylase enzyme

35
Q

what is active form of vitamin D hormone?

A

is calcitriol, also known as 1,25-dihydroxyvitamin D3 or simply 1,25(OH)2D.

36
Q

how is vitamin D transported to kidney for further conversion?

A

by non-specific globulin transport protein, where another cytochrome P450 oxidase enzyme converts it

37
Q

what is the general action of the vitamin D receptor (VDR)?

A

forms a heterodimer with the retinoic X receptor (RXR) on the vitamin D response element on DNA, affecting transcription and the production of proteins for cell diff, developennt, and maintaining normal blood levels of ca ions and phosphate

38
Q

what are some specific examples of the effects of the VDR activation?

A
  • Increases calcium channels in the intestine, facilitating calcium absorption into cells.
  • Increases the expression of calcium-binding protein (calbindin), which transports calcium within the cytosol of cells.
  • Increases the expression of Vitamin D receptor in many cell types.
  • In bone cells, increases the production of osteocalcin, a protein involved in bone formation.
  • Decreases the synthesis of parathyroid hormone in parathyroid cells.
39
Q

what determines the specific transcripts affected by vitamin D receptor?

A

depend on the cell type in which the VDR is expressed

40
Q

what transcriptional changes occur due to vitamin D activity?

A

increases the transcription of ca channels, calcium binding protein, VDR, and osteocalcin (essen protein for bone formation)

41
Q

how does vitamin D affect parathyroid hormone synthesis?

A

decreases it, which helps to keep ca and phosphate in bone

42
Q

what cellular differentiation processes are influenced by vitamin D

A

differentiation of hematopoietic cells, epidermal cells, hair follicle cells, osteoblasts (bone-forming cells), and osteoclasts (bone-resorbing cells)

43
Q

how does vit d influence the balance between osteoblasts and osteoclasts?

A

both vit D and PTH increase expression of RANKL on osteoblasts, which stimulates formation and activation of osteoclasts

  • maintaining balance critical for bone remodeling and bone health
44
Q

parathyroid hormone

A

is a peptide hormone (regulation by transcription, proteolytic
processing and vesicular secretion); made in parathyroid cells of parathyroid gland

45
Q

kidney calcium

A

PTH uses a GPCR where Gαq → PLC → IP3 + DAG that signals Ca 2+
channels to open and uptake from urinary tract and increase plasma Ca 2+

46
Q

bone calcium

A

stimulates osteoclasts (indirectly) causing bone resorption such that
bone releases Ca 2+

47
Q

intestine calcium

A

increases absorption of calcium indirectly via upregulation of active
vitamin D; no PTH receptor in intestine but increases vit D activation in kidney thus
increasing body’s calcium uptake from food

48
Q

how is PTH secretion regulated by extracellular calcium levels?

A

is very sensitive to it, an increase in ion flux into the cell inhibits PTH synthesis and release form secretory granules

49
Q

what receptor mediates the sensitivity of parathyroid cells to EC calcium levels?

A

calcium ion sensor receptor (CaR). is a GPCR that activates the aq pathway and phospholipase C, leading to production of IP3 and DAG, resulting in increase intracellular ca levels

  • increase ca inhibits PTH transcription and secretion
50
Q

what role does intracellular magnesium play in PTH secretion?

A

serves as a secretion signal after stimulation in parathy cells

51
Q

as ca increases…

A

PTH decreases

52
Q

what are the calcitonin effects?

A
  • lowers ca2+ in blood
  • inhibits ca2+ reaborption in kidneys
  • inhibits ca2+ absorption by the intestines
  • promotes deposition of ca2 into bones
53
Q

what are therapeutic uses of calcitonin in humans?

A

used for pagets dz, hypercalcemia, and osteoporosis

54
Q

how does calcitonin exert its main effect on calcium levels in the blood?

A

inhibits osteoclasts, thereby lowering blood calcium levels

55
Q

what is the mechanisms of action of calcitonin?

A

binds to GPCRs on osteoclasts and kidney tubules, activating Gas pathway, which leads to increase in cAMP levels.

  • this inhibits osteoclast activity and reduces calcium absorption from the gut, lowering blood ca levels
56
Q

how is calcitonin secretion regulated?

A

secretion from parafollicular cells (thyroid C cells) is regulated by CaR

  • increased ca levels leads to calcitonin secretion
57
Q

how is PTH secretion stimulated and whats it main role?

A

by low blood ca levels. main role to ensure ca levels in plasma are maintained

58
Q

what are the effects of PTH on calcium levels?

A

enhances ca absorption from food int he gut and urine in kidneys to increase plasma ca levels

59
Q

what is role of calcitonin regulation and how is its secretion stimulated?

A

secreted by thyroid gland C cells, stimualted by high levels of plasma ca. acts to keep ca in the bone by inhibiting osteoclast activity - preventing hypercalcemia and excessive bone loss

60
Q

what are the roles of bone, intestine and kidney in ca regulation?

A
  • Bone acts as a reservoir and buffer for calcium and phosphate.
  • Intestine: Vitamin D increases calcium absorption from the intestine, while calcitonin inhibits calcium absorption indirectly. PTH enhances calcium absorption by activating Vitamin D.
  • Kidney: The kidney conserves calcium and phosphate from urine. Low phosphate, low calcium, and high parathyroid hormone favor the production of 1,25-dihydroxyvitamin D (calcitriol), which enhances calcium absorption. Additionally, hydroxylase deactivates PTH.

BIOL 432 (19 decks)

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