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

Source of Vitamin D

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

How well did you know this?

Not at all

Perfectly

Biosynthesis of Vitamin D3 and its Active Form

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

How well did you know this?

Not at all

Perfectly

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

kidney

How well did you know this?

Not at all

Perfectly

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

skin and immune cells

How well did you know this?

Not at all

Perfectly

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

serum levels of 25(OH)2-D3

How well did you know this?

Not at all

Perfectly

how is 25(OH)2-D3 transported?

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

How well did you know this?

Not at all

Perfectly

Ergocalciferol (vitamin D2)

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

How well did you know this?

Not at all

Perfectly

significance of Ergocalciferol (vitamin D2)

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

How well did you know this?

Not at all

Perfectly

Both ergocalciferol and cholecalciferol undergo conversion to…?

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

How well did you know this?

Not at all

Perfectly

calcitriol

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

often called Vitamin D3

How well did you know this?

Not at all

Perfectly

Vitamin D Receptor (VDR)

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.

How well did you know this?

Not at all

Perfectly

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

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

How well did you know this?

Not at all

Perfectly

Heterodimeric complex

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

How well did you know this?

Not at all

Perfectly

co-activators complex

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.

How well did you know this?

Not at all

Perfectly

in circulation vitamin D is bound to what?

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

How well did you know this?

Not at all

Perfectly

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

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

How well did you know this?

Not at all

Perfectly

what happens to genes induced by biologically active vitamin D3?

involve in transporting calcium ions into blood from gut/diet

How well did you know this?

Not at all

Perfectly

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

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

How well did you know this?

Not at all

Perfectly

Genes positively regulating intestinal transcellular calcium transport (3)

TRPV6
Calbindins
CaATPase

How well did you know this?

Not at all

Perfectly

when vitamin is increased, all transport mechanisms require what?

calcium-binding proteins (Ca-BPs)

How well did you know this?

Not at all

Perfectly

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

collagen
alkaline
phosphatase

How well did you know this?

Not at all

Perfectly

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

1,25-(OH)2-vitamin D3

How well did you know this?

Not at all

Perfectly

what are produced by salivary glands and mucosal epithelium?

antimicrobial peptides

ex. defensins and cathelicidins

Vitamin D3 role

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

Vitamin D levels: deficient, insufficient, normal

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

insufficiency

mild decrease in vitamin D levels

deficiency

greater decrease in vitamin D levels.

what are the main sources for Vitamin D

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

Nutritional rickets and symptoms

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

Vitamin D Dependent Rickets comes in what 2 forms?

type I and type II

Vitamin D Dependent Rickets Type I - age - defect - treatment

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

Vitamin D Dependent Rickets Type II - age - defect - treatment

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

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

type II

signs of rickets

- soft spots on baby's head - bony necklace - curved bones - big,lumpy joints - bowed legs

Osteomalacia

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

Osteomalacia caused by what?

by vitamin D3 deficiency

Hereditary Vitamin D Resistant Rickets (HVDRR)

Mutations with the DBD and LBD

HVDRR patients with mutations in the DBD

have alopecia

HVDRR patients with mutations in the LBD

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

What is psoriasis and its treatment?

Immune mediated disease affecting skin treatment: Vitamin D3

Management of Psoriasis (3)

- topical agents - phototherapy - systemically

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

skeleton, gut and kidney

how are Ca2+ levels in serum sensed?

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

how are Ca2+ levels regulated?

Parathyroid hormone (PTH) and Calcitonin (CT)

Parathyroid hormone (PTH)

- 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

Calcitonin (CT)

produced in parafollicular cells of thyroid | -tones down (decrease) Ca2+ levels

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

increase in active Vitamin D3

Serum Calcium Levels

- Only free (ionized) is physiologically active compartment | - Oral tingling sensation in and around the mouth and lips and in extremities is an early symptom

hypophosphatemia

low serum phosphate levels, very rare due to diet

ionized calcium levels

4.5 – 5.2 | mg/dl

Serum total calcium level

8.8 - 10 | mg/dl

phosphate level

2.5 - 4.5 | mg/dl

magnesium level

1.7 – 2.6 mg/dl

Calcium-Sensing Receptor (CaSR) regulation:

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

Calcium-Sensing Receptor (CaSR) role:

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

what is CaSR encoded by?

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