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Lecture

BIOL 1840U Lecture Notes - Duodenum, Adenylyl Cyclase, Collagen

3 Pages
127 Views
Fall 2012

School
UOIT
Department
Biology
Course Code
BIOL 1840U
Professor
Peter Cheung

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Mineral Metabolism
I. Calcium Balance
a. Fast facts
i. Total body store—1000 gm (1kg)
ii. Ingested daily—1 gm/day
iii. Net uptake—200 mg / day
iv. Net excretion—200 mg/day
b. Body can function on less than the recommended daily dose of Ca, but that requires
energy to extract it more fully and reabsorb it (using PTH & vitamin D action)
c. Recommended Ca Intake
i. High for teens
ii. ~1000 mg for adults
iii. 1500 mg for post-menopausal women b/c intestine is less efficient at absorption
d. Serum Levels
i. Total [Ca] = 10 mg/dl = 2.5 mM
1. ½ total [Ca] is ionized & remainder is bound to albumin or globulin
***Labs measure total [Ca] but hormones only sense ionized Ca
e. Calcium Balance
i. Ca + PO4 (serum) CaPO4 (serum) CaPO4 (bone)
ii. Hormones shift this balance
iii. Kidney makes the fastest changes b/c it filters blood very rapidly (180 L/day)
II. Hormones regulating Ca balance
a. Parathyroid Hormone (PTH)
i. Function—rapidly increases ionize serum [Ca] in response to low [Ca]
1. Ca + PO4 (serum) CaPO4 (serum) CaPO4 (bone)
2. phosphate is lost from kidney (PO4)
3. CaPO4 in bone is mobilized ( resorption)
4. renal Ca reabsorption
ii. Synthesis/ Storage/ Secretion
1. Chief cells of parathyroid gland synthesize PTH
2. 2 cleavages (1st in ER; 2nd in Golgi) => active form
3. stored in secretory granules
4. metabolized in liver & kidneys
iii. [Ca] in serum controls release of PTH
1. Ca => parathyroid gland releases PTH in 3-5 minutes
2. sensed by Ca sensor: low Ca => sensor turns off => [Ca] IC &
transcription of PTH
3. Ca => PTH transcription
iv. Mechanism of Action
1. binds serpentine PTH receptor GPCR cAMP (can be measured in
urine)
v. Cellular Targets
1. Kidney
a. Inhibits PO4 uptake in proximal tubule by removing transporter
(NaPi II) at apical membrane
i. This => [Ca plasma] b/c less is complexed with PO4
b. Increases Ca reabsorption in CCD & DCT by hyperpolarizing
apical mem. (=> nonselective cation/Ca channel opens more)
1

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Description
Mineral Metabolism I. Calcium Balance a. Fast facts i. Total body store—1000 gm (1kg) ii. Ingested daily—1 gm/day iii. Net uptake—200 mg / day iv. Net excretion—200 mg/day b. Body can function on less than the recommended daily dose of Ca, but that requires energy to extract it more fully and reabsorb it (using PTH & vitamin D action) c. Recommended Ca Intake i. High for teens ii. ~1000 mg for adults iii. 1500 mg for post-menopausal women b/c intestine is less efficient at absorption d. Serum Levels i. Total [Ca] = 10 mg/dl = 2.5 mM 1. ½ total [Ca] is ionized & remainder is bound to albumin or globulin ***Labs measure total [Ca] but hormones only sense ionized Ca e. Calcium Balance i. Ca + PO4 (serum) ⇔CaPO4 (serum) ⇔CaPO4 (bone) ii. Hormones shift this balance iii. Kidney makes the fastest changes b/c it filters blood very rapidly (180 L/day) II. Hormones regulating Ca balance a. Parathyroid Hormone (PTH) i. Function—rapidly increases ionize serum [Ca] in response to low [Ca] 1. ↑Ca + ↓PO4 (serum) ⇐CaPO4 (serum) ⇐CaPO4 (bone) 2. phosphate is lost from kidney (↓PO4) 3. CaPO4 in bone is mobilized (↑resorption) 4. ↑renal Ca reabsorption ii. Synthesis/ Storage/ Secretion 1. Chief cells of parathyroid gland synthesize PTH 2. 2 cleavages (1 in ER; 2 in Golgi) => active form 3. stored in secretory granules 4. metabolized in liver & kidneys iii. [Ca] in serum controls release of PTH 1. ↓Ca => parathyroid gland releases PTH in 3-5 minutes 2. sensed by Ca sensor: low Ca => sensor turns off => [Ca] IC ↓& transcription of PTH↑ 3. ↑Ca => ↓PTH transcription iv. Mechanism of Action 1. binds serpentine PTH receptor →GPCR →↑cAMP (can be measured in urine) v. Cellular Targets 1. Kidney a. Inhibits PO4 uptake in proximal tubule by removing transporter (NaPi II) at apical membrane i. This => ↑[Ca plasma] b/c less is complexed with PO4 b. Increases Ca reabsorption in CCD & DCT by hyperpolarizing apical mem. (=> nonselective cation/Ca channel opens more) 1 2. Bone—increases # osteoblasts => increased resorption of bone (turns on osteoclast H+ pumps) b. Calcitonin (CT) i. Function—rapidly lowers ionized plasma [Ca] 1. ↓Ca + PO4 (serum) ⇔CaPO4 (serum) ⇒CaPO4 (bone) 2. ↓renal Ca reabsorption 3. ↓osteoclast resorption ii. Formation/ Storage/ Secretion 1. produced by “C-cells” of thyroid (also by parathyroid & thymus) 2. gene consists of 6 exons generating 2 distinct splice mRNAs a. calcitonin precursor (CT) b. calcitonin gene-related peptide (CGRP)—fxn is vasodilation
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