Question 13

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

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College Answer

This question was best answered under the headings distribution, clearance and physiologic functions.
Distribution involved intracellular vs extracellular concentrations, the spread amongst organ systems
and state of ionisation and protein binding. Clearance of magnesium required an accurate description
of its renal filtration and sites and proportion of reabsorption and secretion along the nephron. The
regulatory factors and factors that influence this clearance should also be outlined. This included; Mg
plasma concentrations, other cations, ECF volume and PTH. Physiologic functions should cover its role
as a cofactor of metabolism and enzyme systems with some examples, the role and mechanism in the
musculoskeletal system as a calcium antagonist and inhibitory action in the nervous system including
the action against Ach, nerves and NMDA activity. 

Discussion

  • Distribution
    • Total: 15 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. 
    • 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)

References

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.