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