Book contents
- Frontmatter
- Contents
- Preface
- Acknowledgements
- Read me first …
- Glossary
- Dedication
- Introduction: A disease for every gene?
- I From molecular biology to human genetics
- II From molecular genetics to human biochemistry
- III From molecular biochemistry to human cell biology
- IV From molecular cell biology to human physiology
- 16 Development
- 17 Metabolism
- 18 Blood
- 19 Immunity
- 20 Neurobiology
- V From molecular physiology to human molecular biology
- Index
17 - Metabolism
Published online by Cambridge University Press: 01 June 2011
- Frontmatter
- Contents
- Preface
- Acknowledgements
- Read me first …
- Glossary
- Dedication
- Introduction: A disease for every gene?
- I From molecular biology to human genetics
- II From molecular genetics to human biochemistry
- III From molecular biochemistry to human cell biology
- IV From molecular cell biology to human physiology
- 16 Development
- 17 Metabolism
- 18 Blood
- 19 Immunity
- 20 Neurobiology
- V From molecular physiology to human molecular biology
- Index
Summary
Bone metabolism
Cholecalciferol regulates calcium metabolism
Calcium is a divalent nonmetal that forms stable compounds such as calcium carbonate (chalk and limestone) and bone (calcium phosphate). Within cells calcium is often ionized, expediting its association with nucleophiles. Calcium can thus function equally well as an extracellular structural element or an intracellular signaling molecule (p. 271). Since only 1% of total body calcium circulates in peripheral blood, major alterations in calcium homeostasis usually reflect the action of bone-interactive cytokines.
Vitamin D is a prohormone that may be synthesized in the skin or ingested. Endogenous vitamin D3 (cholecalciferol) is produced in the skin following UV-induced metabolism of the cholesterol precursor 7-dehydrocholesterol – elevated plasma levels of which occur in a lethal inherited disorder of cholesterol biosynthesis termed Smith–Lemli–Opitz syndrome (7-dehydrocholesterol reductase deficiency).
Measurement of the 25-hydroxy metabolite (25-OHD) is the best indicator of vitamin D deficiency or intoxication. Conversion of this metabolite to the active 1,25(OH)2D (calcitriol) is catalyzed by renal 1α-hydroxylase, a P450 mixed-function oxidase inducible by parathyroid hormone (PTH). PTH inhibits the conversion of 25-OHD to the inactive metabolite 24,25(OH)2D, whereas calcium-independent inhibition of PTH gene transcription by 1,25(OH)2D provides a homeostatic negative feedback loop. An unusual feature of vitamin D is its ability to upregulate its own receptor.
1,25(OH)2D increases intestinal calcium absorption in addition to enhancing both osteoblastic and osteoclastic activity in bone, indicating that its net effect may be to antagonize PTH-mediated bone resorption (Figure 17.2).
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- Human Molecular BiologyAn Introduction to the Molecular Basis of Health and Disease, pp. 415 - 448Publisher: Cambridge University PressPrint publication year: 2002