Question 19

Outline the distribution, clearance and physiologic functions of magnesium in the body.

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College Answer

Insufficient breadth and depth of knowledge limited candidates’ performance to this question. Candidates were expected to mention normal plasma (0.7 – 1.1 mmol/l) and intracellular (20mmol/l) levels, distribution (approximately 50% of total body magnesium is in bone & 20% in skeletal muscles), clearance (almost solely renal, approaches GFR, renal threshold set at just above normal serum Mg concentration, below which get almost  complete reabsorption), activity (e.g. co-factor in metabolism), effects on muscles (reduces muscle excitability, inhibits excitation-contraction coupling, reduced contractility / weakness / depressed reflexes), effects on nerves (e.g. reduces nerve excitability, blocks NMDA receptors), systemic and coronary vasodilation and inhibits platelet function.


  • Distribution
    • Total: 5 mmol/kg.  60%  in bone, 39% is intracellular, 1% is extracellular.
    • Normal intracellular concentration 15-20 mmol/L, extracellular 0.7-1.1 mmol/L
    • In the plasma:
      • 40% is protein-bound (just like calcium)
      • 5-10% is complexed with phosphate lactate citrate, just like calcium
      • about 50-55% is available as free biologically active ion. 
  • Intake
    • 90% paracellular absorption; 10% saturable active transport
    • 30% of dietary magnesium is absorbed in the intestine
    • More is absorbed in states of magnesium depletion
  • Intracellular/extracellular balance
    • Intracellular pool is tightly regulated
    • Extracellular magnesium is exchanged mainly with bone
  • Elimination
    • ​​​​​​​Free magnesium ions are ultrafiltered at the glomerulus
    • 10–15% of the filtered magnesium is reabsorbed in the proximal tubule
    • 60–70% is reabsorbed in the thick ascending limb of the loop of Henle
    • 10-15% is reabsorbed in the distal convoluted tubule
    • DCT process is actively regulated by plasma Mg2+ concentration; reabsorption is near-total at normal magnesium levels, and decreases in hypermagnesemia
  • Physiological function
    • ​​​​​​​Enzyme function: membrane-bound ATPases, kinases, alk phos., enolase
    • Membrane function: cell adhesion, Transmembrane electrolyte flux
    • Structural function: protein folding, polyribosomes, nucleic acids
    • Calcium antagonist: muscle contraction/relaxation, neurotransmitter release (NMDA), action potential conduction, vasodilation/relaxation of smooth muscle
    • Bone metabolism (affects the function of parathyroid hormone)


Vormann, Jürgen. "Magnesium: nutrition and metabolism." Molecular aspects of medicine 24.1-3 (2003): 27-37.

Grubbs, Robert D. "Intracellular magnesium and magnesium buffering." Biometals 15.3 (2002): 251-259.

Raftos, Julia E., Virgilio L. Lew, and Peter W. Flatman. "Refinement and evaluation of a model of Mg2+ buffering in human red cells." European journal of biochemistry 263.3 (1999): 635-645.

Fatholahi, Marjan, et al. "Relationship between total and free cellular Mg2+ during metabolic stimulation of rat cardiac myocytes and perfused hearts." Archives of Biochemistry and Biophysics 374.2 (2000): 395-401.

Vormann, J., et al. "Pathobiochemical effects of graded magnesium deficiency in rats." Zeitschrift fur Ernahrungswissenschaft 37 (1998): 92-97.

Kerstan, D., and G. A. Quamme. "Intestinal absorption of magnesium." Calcium in internal medicine. Springer, London, 2002. 171-183.

Ahmed, Faheemuddin, and Abdul Mohammed. "Magnesium: The forgotten electrolyte—A review on hypomagnesemia." Medical Sciences 7.4 (2019): 56.

Dai, Long-Jun, et al. "Magnesium transport in the renal distal convoluted tubule." Physiological reviews 81.1 (2001): 51-84.

Ryan, Michael F. "The role of magnesium in clinical biochemistry: an overview." Annals of clinical biochemistry 28.1 (1991): 19-26.

Gunther, T.H. "Biochemistry and Pathobiochemistry of Magnesium." (1981).

Maguire, Michael E., and James A. Cowan. "Magnesium chemistry and biochemistry." Biometals 15.3 (2002): 203-210.