Cell Signaling Pathways: Vitamin D3

Examination #2

Is vitamin D a hormone or a vitamin?

Both

Vitamin D3 is known as

Cholecalciferol

Vitamin D3 starts out at ____________ (which is derived from cholesterol), in the ski

7-dehydrocholesterol

7-dehydrocholesterol is sometimes referred to as

Provitamin D3

Provitamin D3 requires metabolic ________ activation to generate the most biologically active form of vitamin D3

Activation

The activation pathway used to form vitamin D3 involves a _______________ activated step, but vitamin D3 can also be obtained from the diet

UV-activated

Vitamin D3 is viewed as a

Prohormone

Vitamin D3 is further metabolized in the liver and then the kidney to generate the di-hydroxylated biologically active form _________

1,25-(OH)₂ D3

1,25-(OH)₂ D3 is known in words as

Calcitriol

___________ products in the US are supplemented with vitamin D3 to help avoid deficiency state

Dairy

Vitamin D3 is required for proper ______ absorption

Calcium and phosphorus

Calcitriol acts through a ___________ receptor

Steroid family nuclear

Vitamin D metabolites are transported in the blood bound to vitamin D binding protein and ________

Serum albumin

Softening of bones in immature (growing) mammals due to deficiency or impaired metabolism of vitamin D, phosphorus, or calcium, potentially leading to fractures and deformity

Rickets

Among the most frequent childhood diseases in many developing countries

Rickets

Softening of bones, similar to rickets, that can also occur in children, but mainly how vitamin D deficiency or impaired metabolism of vitamin D, calcium, or phosphorus manifests in adults

Osteomalacia

Produced by chief cells of the parathyroid gland in response to low calcium levels in the circulation

Parathyroid hormone

Acts to increase Ca²⁺ levels and stimulates production of 1,25-(OH)₂ D3 (calcitriol)

Parathyroid hormone

Opposes the actions of PTH to decrease calcium levels in the serum

Calcitonin

A transcription factor regulating the expression of genes which mediate its biological activity

Vitamin D nuclear receptor

The following genes positively regulate what?

TRPV6

Calbindins

CaATPAse

Intestinal transcellular calcium transport

Which gene is expressed by osteoblasts and is needed to form bone?

Collagen

Calcitriol induces the expression of which transmembrane protein that is rewuired for osteoclast formation?

RANKL

Serve a critical role in mammalian innate immune defense against invasive bacterial infection; broad spectrum antibacterial activity

Calthelicidins

Found in saliva and crevicular fluid where they prevent early colonization by pathogens

Defensins

Vitamin D2 is known as

Ergocalciferol

Vitamin D2 is _______ absorbed compared to vitamin D3

Less

Which form of vitamin D is the best form to elevate serum levels?

Vitamin D3

What dietary substances are particularly high in vitamin D3?

Fish oils

In the liver, cholecalciferol is hydroxylated to form _______

25-(OH) D3

What is the main circulating form of vitamin D3?

25-(OH) D3

In the kidneys, 25-(OH) D3 is hydroxylated to form _______

1,25-(OH)₂ D3

What is the biologically active form of vitamin D3?

1,25-(OH)₂ D3

The hydroxylation of 25-(OH) D3 to 1,25-(OH)₂ D3 carried out by the kidneys does not occur without _______

1-hydroxylase

The expression of 1-hydroxylase is positively regulated by ______

Parathyroid hormone

The physiological actions of regulating intestinal uptake or absorption of calcium ions and as a cell pro-differentiation factor for hair and skin are carried out by _______

Calcitriol

Serum calcium concentration is maintained within a _______ range so as to facilitate normal mineralization of bone and teeth and for nerve transmission and for blood coagulation

Narrow

Vitamin D3 deficiency is associated with increased incidence of _____

Dental caries

Vitamin D3 deficiency is associated with __________ in US men and women over the age of 50

Periodontal attachment loss

Vitamin D helps reduce the risk of caries by producing ________, which are proteins that have antibacterial effects to fight bacteria

Cathelicidin and defensins

The ______ provides the majority of the circulating 1,25-(OH)₂D3

Kidney

Serum levels of _______ are an indicator of how much vitamin D is enetering the body

25-(OH) D3

25-(OH) D3 is trnasported int eh serum by the vitamin D binding protein, _________

Transcalciferin

_________ is a plant/fungi form of vitamin D

Ergocalciferol

Vitamin D2 is _____ acting than vitamin D3

Shorter

Calcitriol binds to the ______________ in target cells to exert its cellular actions

Vitamin D receptor

Calcitriol has the _______ affinity for the vitamin D receptor

Highest

Transcription factor that regulates the expression of genes which mediates biological activity

Vitamin D receptor

After binding 1,25-(OH)₂D3, VDR forms a heterodimeric complex with other nuclear hormone receptors, particularly the ________________

Retinoid-x-receptor

The VDR/RXR complex binds to the DNA promoter sequences containing the ______ sequences in genes it regulates

VDRE

In the gut, calcitriol increases the expression of TRPV6, calbindin D9K, and  Ca²⁺ATPase1b, which will in turn increase __________ uptake

Calcium

Facilitated diffusion of calcium ions into the cell on the apical surface

TRPV6

Transports calcium transcellularly from the apical surface to the basal surface

Calbindin D9K

Pumps calcium out of the cell and into the capillaries on the basal surface

Calcium ATPase 1b

Active agent that causes caries in humans

S. mutans

Active agent commonly implicated in periodontal disease

P. gingivalis

The major role of vitamin D3 is the control of _______ homeostasis in circulation

Calcium

Vitamin D levels below 20 ng/ml are considered

Deficient

Vitamin D levels between 20-29 ng/ml are considered

Insufficient

Vitamin D levels above 30 ng/ml are considered

Normal

Impaired bone mineralization due to a deficiency in vitamin D

Rickets

Classic symptoms of this disease include leg bowing and rachitic rosary

Rickets

VDDR type 1 is nicknamed

Pseudovitamin D deficient rickets

VDDR type 2 is nicknamed

Hereditary vitamin D resistance

VDDR type 2a is caused by an inactivating mutation in the

Nuclear vitamin D receptor

In which type of rickets is the primary defect in the renal vitamin D 1-hydroxylase?

VDDR type 1

Due to the defect in 1-hydroxylase in VDDR type 1, the main circulating form of vitamin D3 cannot be converted into the ______________

Biologically active form

In which type of rickets is the primary defect int eh vitamin D receptor?

VDDR type 2

In VDDR type 2, there is a high amount of the ________ circulating because the vitamin D receptor is not responding to it

Calcitriol

Softening of the bones due to inadequate levels of calcium and phosphate, which is commonly due to vitamin D deficiency

Osteomalacia

One way that rickets can manifest orally is by ________

Enamel hypoplasia

Calcium levels in the serum are sensed by the parathyroid gland through the _______

Calcium sensing receptor

Ca²⁺ and phosphate levels are regulated largely by the actions of

Parathyroid hormone

PTH is produced by

Chief cells of the parathyroid

Calcitonin is produced by

Parafollicular cells of the thyroid

PTH acts to _______ calcium levels

Increase

Calcitonin acts to ______ calcium levels

Decrease

The actions of PTH on intestinal uptake of Ca²⁺ and phosphate is largely mediated by the

increase in active vitamin D3

Only free (ionized) calcium is physiologically active

Serum calcium levels

Main function is to maintain the concentration of ionized calcium in the serum and extracellular fluid

Parathyroid hormone

There are two parathyroid receptors: PTH1R and PTH2R

Which receptor is involved in calcium homeostasis?

PTH1R

PTHrP is a closely related homolog of PTH. Which receptor will bind to both of PTH and PTHrP?

PTH1R

The calcium sensing receptor (CaSR) is activated by

Extracellular calcium

The calcium sensing receptor (CaSR) regulates

PTH secretion in the thyroid

What type of receptor is CaSR?

G-protein coupled

When calcium decreases, PTH production ______

Increases

When calcium increases, PTH production _________

Decreases