metabolism - vitamin d

how does vitamin d help maintain serum Ca concentrations within normal levels (3 ways)?

1) increases intestinal Ca & P absorption 2) increase osteoclast activity in response to PTH (increase osteoblast RANKL expression to increase osteoclast formation) 3) increase Ca reabsorption in kidney

active, hormonal form of vitamin D

1,25(OH2)D

calcitriol

1,25(OH2)D

1 ng/dL = ? nmol/L

2.5 nmol/L

most people in U.S. have a vitamin D status of __-__ ng/mL, indicating that their status is ________

20-30 sufficient

what enzyme degrades 25(OH)D + 1,25()H2)D

24-hydrozylase

calcidiol

25(OH)D

what is the best marker of vitamin D status?

25(OH)D

active form of vitamin D regulates ___% of human genome

3

there is very little vitamin d skin synthesis at latitudes above ____N or below ____ S of equator

37, 37

1 ul = ? IU

40 IU

___-____ min of sun exposure ___x/week is usually adequate

5-30 2x

_____________ is synthesized by skin cells

7-dehydrocholesterol (DHC)

by age 70, skin production of vitamin D is reduced by ____% due to __________

75% d/t reduced ability to convert to active form of vitamin D & reduced intestinal Ca absorption

RDA for ages 71+ is higher at ______ vs _______ for younger groups

800 IU 600 IU

vitamin D deficiency means decreased _____ absorption & elevated _____ levels

Ca PTH

vitamin D DRI is based on these outcomes

Ca absorption BMD risk of osteomalacia risk of rickets

1,25(OH2)D from the kidney contributes to (list)

Ca homeostasis muscle & bone health BP regulation CV health neurodevelopment immunomodulation

classical function of vitamin D

Ca/P absorption & prevention of rickets

in the WHI trial, there was an increase in hip bone density in which group?

D/Ca supplemented group

1,25(OH2)D participates in transcellular Ca absorption by increasing expression of _________ & __________

TRPV6 calbindin

25(OH)D circulates in plasma bound to

VDBP

major plasma carrier of all vitamin D metabolites

VDBP

1,25(OH2)D-_______ complex binds to _______, forming heterodimer that interacts with __________

VDR RXR VDRE--vitamin D response element

____-_____ binding to _____ attracts co-activator proteins to initiate _________

VDR-RXR VDRE gene transcription

what is required for vitamin D supplementation to be beneficial?

adequate Ca intake

vitamin d is sequestered in ___________ but not stored or released in response to low serum vitamin D

adipose tissue

osteomalacia is ____-onset because _________

adult growth plates are closed in adults so skeletal deformities seen in rickets are not present

synthesis in skin depends on

age, latitude, season, skin color, clothing, sunscreen

ergo/vitamin D2 is not synthesized by

animals & humans

disorders in which intestinal Ca absorption is too low to match Ca demands imposed by bone growth

calcipenic rickets

dietary vitamin D is packaged into _______________ with __________ + __________

chylomicrons TG cholesterol

skeletal abnormalities of rickets are a result of

decreased Ca absorption

what happens in hyperparathyroidism?

elevated PTH levels = body is working very hard to bring up serum Ca levels

ergo/vitamin D2 is produced from precursor _____________ by (list) in response to ___________

ergosterol phytoplankton, yeast, invertebrates, fungi UV irradiation

goal of WHI trial was to

evaluate impact of supplementation on fracture risk in a vitamin D/Ca supplements group vs placebo

best dietary sources of vitamin D

fatty fish, cod liver oil

altered biochemistry seen in calcipenic rickets

high PTH, low vitamin D

toxicity is usually only a result of

high supplement use

chemical substance produced in body to control & regulate cellular activity

hormone

In the liver, vitamin D is _______________ to ____________

hydroxylated 25(OH)D

vitamin D toxicity can lead to

hypercalcemia

abnormal labs in osteomalacia

hypocalcemia, hypophosphatemia, increased serum bone alkaline phosphatase

1,25(OH2)D from the monocytes & macrophages from liver contributes to

immunomodulation

what is the feedback loop in vitamin D catabolism?

increased 1,25(OH2)D increases 24-hydroxylase expression

how is BMI associated with changing 25(OH)D after supplementation?

inversely

25(OH)D is transported to the _______________ + hydroxylated a second time to _______________

kidney 1,25(OH2)D

circulating vitamin D is taken up by the

liver

there is a more significant change in serum vitamin D after supplementation in those with a (higher/lower) BMI

lower

osteomalacia characterized by

poor mineralization of collagen matrix

7-DHC is converted to ______________ by ____________

pre-vitamin D UV radiation

Pro D3 --> _______ --> vitamin D3 --> liver --> _______ --> kidney + PTH + low P --> __________ --> intestines & bone

preD3 25(OH)D 1,25(OH2)D

osteomalacia symptoms

reduced BMD, increased fracture risk, deep bone bain

why is 25(OH)D the best marker of vitamin D status?

reflect sun & diet 1,25(OH2) D is tightly regulated by serum Ca & P 25(OH)D has a longer half-life (21 days) than active form (4 hours)

1,25(OH2)D in prostate gland, breast, colon, lung, & keratinocytes contributes to

regulation of cell growth & differentiation

symptoms of calcipenic rickets

short stature, widening at ends of long bones, bony necklace, skeletal deformities, bowed legs, knocked knees, soft spot on baby's head slow to close, curved bones

cholecalciferol/vitamin D3 is produced in ____________ when exposed to ___________

skin of vertebrate animals UV irradiation

prevention of calcipenic rickets

supplementation of BF infants with 400 IU/day liquid vitamin D drop

what about TRPV6 & calbindin are responsive to vitamin D?

the genes coding for them

pre-vitamin D undergoes __________ ______________, forming ____________

thermal isomerization vitamin D3

vitamin D3 enters circulation bound to

vitamin D binding protein (VDBP)

most common cause of calcipenic rickets

vitamin D deficiency

DNA sequence in promotor region of a vitamin D responsive gene

vitamin D response element (VDRE)

ergocalciferol

vitamin D2

cholecalciferol

vitamin D3

which form is more effective at raising serum 25(OH)D?

vitamin D3 (slightly)

an individual with dark skin may require up to ___x sun exposure as someone with light skin

10

osteomalacia is associated with a very low serum 25(OH)D of <____ ng/mL

10

serum concentrations >____-_____ ng/mL raise concern for toxicity

100-150

a supplement dose of ___-___ ng/mL shows improved outcomes in the above categories, but above ____ ng/mL has now shown to be beneficial

12-20 20

potential adverse effect of vitamin D/Ca supp

17% increased risk of kidney stones (WHI)

what increases expression of renal a-hydroxylase enzyme?

PTH

__________ absorb UV rays, preventing vitamin D synthesis

melanins

serum concentration is expressed in _____ or _____ (units)

nmol/L ng/dL

is vitamin D deficiency common in US?

no

was there a benefit of taking vitamin D supplements in terms of cancer or CV events?

no