Vitamin D metabolism

From Ganfyd

The metabolic pathways involved in the formation of the various Vitamin D pro-hormones are complex and in man limited by the need for ultra violet light formation of Vitamin D3 itself. The final steps to form active hormone depend upon kidney cytochrome pathways. The main Vitamin D3 pathway in man is detailed here while the relevant overview of human steroid metabolism is here.

For some of the year in high latitudes the oblique rays of the sun include too little ultra-violet at ground level to synthesise much Vitamin D even in populations evolved to make the most of it.

Production

• Vitamin D (dietary) converted to D3 by photochemical reaction in skin
• D3 converted to 25-hydroxy D3 in liver
• 25-(OH)D transported to kidney where it is hydroxylated to 1,25-(OH)₂D or 24,25-(OH)₂D

Controls

• increased by fall in serum calcium
• increased by fall in serum phosphate
• 1-alpha-hydroxylation in kidney increased by parathyroid hormone

Others

• 1,25-(OH)₂D inhibits 25-(OH)D production (negative feedback)
• 1,25-(OH)₂D inhibits parathyroid hormone secretion through raised serum calcium levels, thereby suppressing its own production.

Actions

• Increases calcium and phosphate concentrations in blood
  • Increased reabsorption of calcium and phosphate in gut
  • Increased reabsorption of calcium in kidney
  • parathyroid hormone (PTH) dependent reabsorption of bone

Tissues Involved

• intestine
  • cytosolic/nuclear receptor
  • stimulates protein production (such as Ca⁺⁺ binding protein)
• kidney,
  • increases renal tubular absorption of calcium and phosphate
• bone
  • produces bone reabsorption
  • affect potentiated by parathyroid hormone
  • important in ordered remineralisation of bone

Disorders

• excess 1,25-(OH)₂D leading to hypercalcaemia, weakening of bone
• deficiency in 1,25-(OH)₂D causes hypocalcaemia and bone weakening
  • rickets / osteomalacia
    • failure of receptor for 1,25-(OH)₂D leads to rickets or osteomalacia (rickets =children, osteomalacia = adult)