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Biochem Quiz #2 (part 1/2 for exam #2) > 9/16/2021 Cell signaling pathways: steroid hormones (Vitamin D3) > Flashcards

9/16/2021 Cell signaling pathways: steroid hormones (Vitamin D3) Flashcards

1
Q

Source of Vitamin D

A

Bare skin exposure 5-10 minutes
2-3 times per week
(depends upon time of year and latitude)

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2
Q

Biosynthesis of Vitamin D3 and its Active Form

A

Skin->Provitamin D3-> Previtamin D3->Vitamin D3-> 25(OH)D3-> biologically active form

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3
Q

what organ process the majority of the circulating 1,25(OH)2-D3

A

kidney

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4
Q

what synthesizes 1,25(OH)2-D3 for an autocrine or paracrine mechanism

A

skin and immune cells

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5
Q

what is an indicator of how much Vitamin D is entering the host?

A

serum levels of 25(OH)2-D3

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6
Q

how is 25(OH)2-D3 transported?

A

in serum by Vitamin D binding protein (DBP) OR transalciferin (TC)

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7
Q

Ergocalciferol (vitamin D2)

A

plant/fungi form and most commonly found in dietary supplements and fortified foods

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8
Q

significance of Ergocalciferol (vitamin D2)

A

less absorbable, less potent and shorter acting than cholecalciferol (vitamin D3) and therefore the best “vitamin” supplements contain cholecalciferol.

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9
Q

Both ergocalciferol and cholecalciferol undergo conversion to…?

A

25(OH)-Vitamin D and 1,25-(OH)2-Vitamin D.

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10
Q

calcitriol

A

active form of 1,25(OH)2-Vitamin D (aka 1,25(OH)2D3)

often called Vitamin D3

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11
Q

Vitamin D Receptor (VDR)

A
  • mediates the nuclear actions of 1,25(OH)2D3.
  • a transcription factor regulating the expression of genes which mediate its biological activity

affinity of the receptor varies dramatically with 1,25(OH)2D3 having the highest affinity by several log orders.

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12
Q

what does VDR form before binding to 1,25-(OH)2-Vitamin D3

A

forms a heterodimeric complex with other nuclear hormone receptors, particularly the Retinoid-X-Receptor (RXR). `

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13
Q

Heterodimeric complex

A

binds to DNA promoter sequences containing the VDRE (Vitamin D response element) sequences in genes it regulates.

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14
Q

co-activators complex

A

addition protein that are with activated VDR/RXR heterodimers to recruit the proteins required for transcription such as RNA polymerase II to the transcription start site.

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15
Q

in circulation vitamin D is bound to what?

A

globulin–transcalciferin (TC) within only a small fraction existing in free form

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16
Q

action of free form of vitamin D? and what will be induced?

A

vitamin D interacts with VDR; induces dimerization with RXR to result in stimulation or inhibition of gene transcription.

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17
Q

what happens to genes induced by biologically active vitamin D3?

A

involve in transporting calcium ions into blood from gut/diet

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18
Q

Vitamin D3 induce Ca2+ absorption in gut (enterocyte to basolateral surface)

A

(enterocyte) From TRPV6 Ca2+ channel->Ca2+ enters bursh border microvilli thru Ca2+ channels-> Calbindin transport proteins-> endocytosis and exocytosis of Ca2+-CaBP complex

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19
Q

Genes positively regulating intestinal transcellular calcium transport (3)

A
  1. TRPV6
  2. Calbindins
  3. CaATPase
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20
Q

when vitamin is increased, all transport mechanisms require what?

A

calcium-binding proteins (Ca-BPs)

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21
Q

what genes are expressed by osteoblasts are needed to form bone (3)?

A
  1. collagen
  2. alkaline
  3. phosphatase
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22
Q

what can induce the expression of RANKL, which is required for osteoclast formation?

A

1,25-(OH)2-vitamin D3

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23
Q

what are produced by salivary glands and mucosal epithelium?

A

antimicrobial peptides

ex. defensins and cathelicidins

24
Q

Vitamin D3 role

A
  • control of Ca2+ homeostasis in the circulation.
  • phosphorus absorption
  • Adequate levels are needed for the development of strong bones and teeth
25
Q

Vitamin D levels: deficient, insufficient, normal

A

Deficient: 20 ng/ml
Insufficient: 20-29 ng/ml
Normall: 30+ ng/ml

26
Q

insufficiency

A

mild decrease in vitamin D levels

27
Q

deficiency

A

greater decrease in vitamin D levels.

28
Q

what are the main sources for Vitamin D

A

fish oils and fortification, which means food that has extra nutrients added to it

29
Q

Nutritional rickets and symptoms

A

Vitamin D or calcium or phosphate deficiency

symptoms: prominence of the costochondral junction (rachitic rosary), deformities of the back and bowing of the legs, softened calvarium, parietal flattening, frontal bossing and delayed eruption of the permanent dentition and enamel defects

30
Q

Vitamin D Dependent Rickets comes in what 2 forms?

A

type I and type II

31
Q

Vitamin D Dependent Rickets Type I

  • age
  • defect
  • treatment
A

Age: Occurs early by age 2 and during first 6 months of life
Defect: 25(OH)D 1-hydroylase; Low circulating 1,25 (OH)2D3
Treatment: massive doses of vitamin D or 25(OH) D3, or lower doses of 1,25 (OH)2D3

32
Q

Vitamin D Dependent Rickets Type II

  • age
  • defect
  • treatment
A

Age: Normal at birth, bone disease usually before age 2
Defect: Normal or high circulating levels of 1,25(OH)2 D3
Treatment: high dose 1,25(OH)2D3 and up to 3 gm Calcium per day

33
Q

what type of Vitamin D Dependent Rickets is commonly obseved with alopecia, multiple milia, epidermal cysts and oligodontia

A

type II

34
Q

signs of rickets

A
  • soft spots on baby’s head
  • bony necklace
  • curved bones
  • big,lumpy joints
  • bowed legs
35
Q

Osteomalacia

A

softening of the bones due to inadequate levels of calcium and phosphate, which are most commonly due to Vitamin D deficiency.

36
Q

Osteomalacia caused by what?

A

by vitamin D3 deficiency

37
Q

Hereditary Vitamin D Resistant Rickets (HVDRR)

A

Mutations with the DBD and LBD

38
Q

HVDRR patients with mutations in the DBD

A

have alopecia

39
Q

HVDRR patients with mutations in the LBD

A

that affect ligand-binding or co-activator-binding do not have alopecia.

40
Q

What is psoriasis and its treatment?

A

Immune mediated disease affecting skin

treatment: Vitamin D3

41
Q

Management of Psoriasis (3)

A
  • topical agents
  • phototherapy
  • systemically
42
Q

what parts of the body plays critical roles in the maintenance of serum Ca2+

A

skeleton, gut and kidney

43
Q

how are Ca2+ levels in serum sensed?

A

by the parathyroid gland through the calcium-sensing receptor (CaSR)

44
Q

how are Ca2+ levels regulated?

A

Parathyroid hormone (PTH) and Calcitonin (CT)

45
Q

Parathyroid hormone (PTH)

A
  • produced by the chief cells of the parathyroid
  • increase Ca2+ levels

increase in phosphate excretion through the urine, but enhances uptake of phosphate from the intestine and skeleton into the circulation

46
Q

Calcitonin (CT)

A

produced in parafollicular cells of thyroid

-tones down (decrease) Ca2+ levels

47
Q

how is intestinal uptake of Ca2+ and phosphate largely mediated?

A

increase in active Vitamin D3

48
Q

Serum Calcium Levels

A
  • Only free (ionized) is physiologically active compartment

- Oral tingling sensation in and around the mouth and lips and in extremities is an early symptom

49
Q

hypophosphatemia

A

low serum phosphate levels, very rare due to diet

50
Q

ionized calcium levels

A

4.5 – 5.2

mg/dl

51
Q

Serum total calcium level

A

8.8 - 10

mg/dl

52
Q

phosphate level

A

2.5 - 4.5

mg/dl

53
Q

magnesium level

A

1.7 – 2.6 mg/dl

54
Q

Calcium-Sensing Receptor (CaSR) regulation:

A

regulates the release of parathyroid hormone (PTH) produced by the parathyroid

55
Q

Calcium-Sensing Receptor (CaSR) role:

A

control of reabsorption of Ca2+, phosphate, Na+ and water in kidney

56
Q

what is CaSR encoded by?

A

the CASR gene and is a G-protein coupled receptor.

Biochem Quiz #2 (part 1/2 for exam #2) (4 decks)

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