wk 12, lec 1 Flashcards
2 forms of vitamin D and where re they obtained from
- Vitamin D2 (ergocalciferol)
- Vitamin D3 (cholecalciferol)
D2=diet
D3=skin via sun
vitamin D synthesis
UVB exposure causes 7-dehydrocholesterol in skin to be converted into provitamin D3 –> D3 cholecalciferol
transport to liver: via blood and undergo hydroxylation by enzyme 25- hydoxylase to become 25-hydroxyvitamin D (calcidiol or 25(OH)D)
transport to kidneys: 25-hydroxyvitamin D undergoes another hydroxylation via 1-alpha-hydroxylase; add hydroxyl group in proximal tubule ONLY WHEN stimulated by PTH –> form calcitiriol (1,25-
dihydroxyvitamin D or 1,25(OH)2D) which is biologically active
steps of vitamin D synthesis from UVB
in skin: D3 cholecalciferol
then 2 hydroxylations
in liver: form 25-hydroxyvitamin D (calcidiol or 25(OH)D)
[[via 25-hydroxylase]]
in kidney: form Calcitriol (1,25-
dihydroxyvitamin D or 1,25(OH)2D),
[[via 1-alpha-hydroxylase]]
calcitriol (active form of vitamin D3) synthesis is regulated by? and what do they influence?
- Parathyroid hormone (PTH)
- Serum calcium levels
- Fibroblast growth factor 23 (FGF23)
Influence the activity of 1-alpha-hydroxylase.
impact of high and low serum calcium on calcitriol production
i.e. low Ca2+ stimulates PTH which stimulates 1-alpha-hydroxylase to increase calctriol production
high Ca2+ and high FGF23 inhibit 1-alpha-hydrpxylase to reduce calcitriol production
calcitriol functons
-intestinal absorption of calcium and phosphorus (via cal binding-D protein expression)
-bone health (mineralization by stimulating phosphorus and calcium deposition)
-renal reabsorption (regulate Ca2+ and P)
-PTH regulation
low Ca2+ ____ to PTH
increases PTH secretion –> increase vitamin D
causing a mobilization of calcium from bone and intestines
negative feedback loop
calcium and location
majority in bone; a bit in GI/blood
lost in feces from diet; gastric juices
calcium in bone formation
calcium phosphate crystals;
hydroxyapatite crystals
osteoblasts secrete osteocalcin and osteopontin to bind to calcium ions
osteocalcin and osteopontin act as nucleation sites for calcium phophate crystals
Ca2+ and phosphate ions combine to form crystals –> deposit into collagen in bone matrix
osteoblasts secrete ___ and. ____ to bind to calcium ions
osteocalcin and osteopontin
3 hormones that regulate calcium levels in body
- Parathyroid Hormone (PTH)
- Calcitonin
- Calcitriol
how PTH affects calcium
low serum Ca2+ –> production of PTH –> stimulates osteoclasts –> bone resorption and release Ca2+ into blood
enhance renal reabsorption of ca2+ in kidney (less urinary excretion)
stimulate calcitiriol (vitamin D) production in kidney (promote intestinal absorption of calcium)
calcitonin and PTH relationship
OPPOSITE
calcitonin via high Ca2+
PTH via low serum Ca2+
calcitonin impact on calcium
high Ca2+ –> calcitonin secretion from thyroid
inhibit osteoclasts; promote bone deposition of ca2+
suppress renal tubular reabsorption of calcium, increase urinary excretion
vitamin D (calcitriol) impact on calcium
increase intestine absorption (protein express for active transport)
promote bone mineralization and increase ca2+ deposition
regulate renal reabsoprtion of ca2+ and phosphorus
actions of PTH, calcitriol and calcitonin impacting calcium
- PTH increases plasma Ca2+ by mobilizing this ion from bone
- It increases Ca2+ reabsorption in the kidney, but this may be offset by
the increase in filtered Ca2+ - It also increases the formation of 1,25-dihydroxycholecalciferol
(Calcitriol) - Calcitriol increases Ca2+ absorption from the intestine and increases
Ca2+ reabsorption in the kidneys - Calcitonin inhibits bone resorption and increases the amount of Ca2+ in
the urine.
phosphorus roles in the bone
mineralization of bone matrix (hydroxyapatite crystals)
phosphate needed for synthesis of osteoblast proteins like osteocalcin and osteopontin
high phosphate inhibits osteoclasts, low phosphate stimulates osteoclasts
acts as buffer to maintain pH in bone
regulate gene expression in bone
PTH and calcitriol for phosphorus metabolism
PTH impact on phosphorus
PTH increases blood phosphorus levels by promoting its release from
bone tissue and enhancing its reabsorption in the kidneys
2 forms of vitamin K and where they are found
- Vitamin K1 (phylloquinone)
- found in green leafy vegetables
- Vitamin K2 (menaquinone)
- synthesized by bacteria in the gut and found in fermented foods
and animal products
vitamin K synthesis b ia gut bacteria
bacteria convert dietary precursors, such as phylloquinone
(vitamin K1) and menadione (a synthetic form of vitamin K), into
menaquinones (vitamin K2)
absorption of vitamin K1
then transport and conversion
in the small intestine, along with dietary
fats, through a process that requires bile salts and pancreatic enzymes
transport via lymph into blood into liver and then get converted into active form
vitamin K impact on bone metabolism
carboxylation of osteocalcin (protein made by osteoblasts) ; turns it into active from where it binds ca2+ ions and promotes deposition into bone
bone mineral density
osteoblast function
how does PTH regulate calcium in blood?
It does this through:
* Calcium mobilization from bone
* Absorption from the intestines
* Reabsorption in the kidneys
- PTH stimulates osteoclast activity, leading to bone resorption and subsequent release of calcium into the bloodstream
PTH impact on bone
increase bone resorption; mobilize ca2+
increase phosphate excretion in urine
–> phosphaturic action via NaPi-IIa in proximal tubules
-increase ca2_ reasbortption in distal tubules
PTH also increases the formation of 1,25-dihydroxycholecalciferol, and this
increases Ca2+ absorption from the intestine