Summary
In 1969, McCully concluded that homocysteine is a causative agent in arterioscleosis [1]. A recently concluded study of 1,041 people from the Framingham Heart Study found that elevated plasma homocysteine leads to an increased risk of arteriosclerosis [2]. Other studies [2] have linked even moderate hyperhomocysteinemia to peripheral vascular, cerebrovascular, and coronary heart disease. Although vitamin B12, vitamin B6, and folate therapy have been suggested to lower hyperhomocysteinemia, acute medical intervention may be indicated for a large fraction of individuals at risk for this disease.
We propose the enzyme methioninase as a potential therapeutic for acute intervention to immediately lower homocysteine levels. Methioninase has been recently isolated in pure form [3] and cloned [6] from Pseudomonas putida and is now in Phase I clinical trials for the treatment of cancer [7, 8]. Methioninase lowers circulating methionine levels in mice and humans from 30-100 μM to less than 1 μM and homocysteine levels in mice and humans to under 1 μM with no apparent toxic side effects and well below cardiovascular toxicity levels (7, 8).
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References
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Hoffman, R.M. (1997). Is Methioninase Useful for the Prevention of Hyperhomocysteinemia-Associated Cardiovascular Disease?. In: Graham, I., Refsum, H., Rosenberg, I.H., Ueland, P.M., Shuman, J.M. (eds) Homocysteine Metabolism: From Basic Science to Clinical Medicine. Developments in Cardiovascular Medicine, vol 196. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5771-5_21
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DOI: https://doi.org/10.1007/978-1-4615-5771-5_21
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