Biomathematics & Statistics Scotland
The methionine-homocysteine cycle plays an important role in a range of key metabolic reactions. Impairment of this cycle leads to high homocysteine concentrations in the plasma, which is associated with increased risk of cardiovascular disease. What is not understood is why increased plasma concentrations arise: are they the result of increased rates of production, reduced rates of removal of homocysteine, or a combination of the two? Likewise, little is known about which tissues are involved in these production and removal processes. To investigate these issues in detail, studies were conducted using stable isotopes to trace methionine and homocysteine activity. Mathematical models were developed that describe the movements of the stable isotope tracers between plasma and the various tissues as well as cycle activity within the tissues. This allowed for identification of two key tissues, with the pancreas being the main tissue that exports homocysteine into the plasma, and with the heart playing a major role in uptake of homocysteine from the plasma, providing further evidence for a link between high plasma homocysteine concentrations and cardiovascular disease.
Pictorial representation of the methionine-homocysteine cycle in the heart and the
pancreas, linked by transport through blood vessels.
The system is governed by mass balance equations.
For each tissue:
rate of input + rate of production
= rate of output + rate of conversion.
Further details from: Grietje Holtrop
Article date 2009
