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Lecture

Mineral Metabolism I

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School
Department
Biology
Course
BIOL 1840U
Professor
Peter Cheung
Semester
Fall

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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