Pathophysiology of Abdominal Aortic Aneurysm – Genetic Factors and Homocysteine Metabolism

Homocysteine (Hcy) is a non-protein amino acid resulting from the demethylation of the essential amino acid methionine. This is an important step in the metabolism of nucleic acids, fats and high-energy bonds and for this reason, the transmethylation reaction of Hcy back to methionine requiring Vitamin B12 and folic acid, is equally important. This pathway is dependent on a form of folate produced by methylenetetrahydrofolate reductase (MTHFR). Hcy can also be metabolised to cystathionine, an intermediate of the non-essential amino acid cysteine. Vitamin B6 is necessary for this transulphuration reaction to occur (Figure 1) (Warsi et al, 2004; Guilliams, 2004; Moroz et al, 2007; Castro et al, 2006) Excess levels of Hcy are excreted to the plasma where the liver and kidney are the organs achieving catabolism and excretion of Hcy. Despite this, mild hyperHcy is present in 5-7% of the general population, due to either inherited or acquired dietary deficiencies of vitamin B6, B12 and folic acid. Other causes include renal failure, malignancy, hypothyroidism and use of folate and vitamin B6 antagonists (Halazun et al, 2007).