L7.HormControl of MinMetabolism Flashcards
(13 cards)
In extracellular fluid and cytosol, what is the relative/approximate balance that must be maintained?
Need much higher concentration of Ca in ECFluids ([Ca]=2.5), than in the cytosol ([Ca]=0.001).
What cells are the Calcium receptors in the Parathyroid gland found in?
What cells in the thyroid gland?
Chief Cells.
C-cells.
What are the 3 levels of response to low [Ca] by the parathyroid gland?
- release prestored PTH
- Increase PTH expression
- PTG cell proliferation
Is the PTH released as active or inactive? What has to happen to activate or inactivate the PTH?
PTH’s aa sequence is 84 aa long what happens if you cleave off everything after aa 34?
Inactivate. Must cleave propeptide
Nothing first 34 aa is the catalytic region and w/o the rest function is not altered.
PTH binds to what specific, G-protein linked plasma membrane receptor? What enzyme-signalling pathway is this receptor linked to?
PTH1R. Linked to adenylate cyclase, which results in increased intracellular cAMP
What is PTHrP? What receptor does it bind? What processes is it involved in? Where is it found?
PTHrP = ParaThyroidHormone related Protein.
- PTHrP is a growth AND differentiation factor.
- PTHrP binds to PTH1R (same receptor as PTH)
- PTHrP is involved in para/autocrine actions in many fetal and adult tissues, especialy chondrocytes, where the PTH1R mediates the PTHrP-dependent regulation of growth plate chondrocyte proliferation & differentiation.
What is the mechanism by which PTH and 1,25-(Ca)2-D increase bone resorption?
They upregulate RANKL production in OSTEOBLASTs, which is an essential receptor in the maturation process of osteoclasts. Thus, more osteoclasts mature and bone resorption is increased.
PTH may actually be used in the treatment of osteoperosis. How is this?
When PTH is given in intermittent high doses it actually has anabolic effects instead of catabolic function like it does at constant levels. This results in increased bone formation.
What is the metabolic process to synthesize Vit D2 (plant derived) & D3 (Cholesterol derived, UV rays break b-ring of cholesterol steriod) to 1,25-(OH)2-D? 2 steps.
Overall: 2 hydroxylations, 1 in liver, 1 in kidney
- Liver: Vitamin D 25 Hydroxylase = A CYP (Cytochrome-p450) enzyme that requires NADPH & O2. Vit D –> 25-(OH)-Vit D.
- Not well regulated. Converts all Vit D comes in contact with in liver. - Kidney: Vitamin D 1 Hydroxylase (Also, NADPH, O2 requiring CYP). 25-(OH)-D –> 1,25-(OH)2-D Via hydroxylation rxn.
- Regulated by PTH & P04 concentrations.- Increase [PTH] –> increase D1 hydroxylase act
- Decrease [P04] –> increase D1 hydroxylase act
Rickets and osteomalacia are caused by what vitamin defficiency?
Vit D
What are the two mechanisms by which Vitamin D is thought to carry out its actions?
- VDR = Vitamin D receptors
- Part of steroid/thyroid hormone receptor family
- Basically, 1,25D binds to VDR, VDR activates VDRE (VitaminD Response Elements = transcription factors), VDRE activates gene transcription.
- Slow hormonal Mechanism - Nongenomic mechanism: May act directly by disrupting plasma membranes of target cells. Many of its anti-tumor effects are though to act by this mechanism. Fast acting.
What are the 3 methods of calcitonin action?
- Acts directly on osteoclasts to inhibit bone resorption
- Acts on kidney to increase excretion of Ca and PO4 (only at high levels)
- Upregulates expression of D-24-hydroxylase, which inhibits 1,25-(oh)-D
How does FGF23 effect phosphate concentration? How do PHEX and Dentin Matrix Protein-1 (DMP-1) effect FGF23 levels?
Promotes PO4 excretion in kidney after being produced by osteocytes in bones.
PHEX and DMP-1 suppress FGF23 expression in bones.
