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Research
Enzymology and Sulfur Amino Acid Metabolism |
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| My research focuses on exploring the mechanism and regulation of the enzymes involved in sulfur amino acid regulation in plants, humans, and microorganisms. We use an array of methods including molecular biology, enzyme kinetics, and biophysical spectroscopy. Techniques applied include: PCR and real-time PCR, site-directed mutagenesis, steady state and presteady state kinetics, stopped-flow, circular dichroism spectroscopy, fluorescence spectroscopy, Fourier transform infrared spectroscopy, isothermal titration calorimetry, and analytical ultracentrifugation, to name a few. This research has important agricultural, medical, and biotechnology applications, including: |
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1. Biosynthesis of methionine in plants
2. Phytoremediation of soil contaminated by heavy metals
3. Enzyme engineering and biotechnology
4. Homocysteine metabolism
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1. Biosynthesis of methionine in plants
Legumes tend to be deficient in the essential amino acid methionine and are therefore an incomplete source of protein for human consumption. The development of new varieties of legume crops with increased levels of methionine would be of economic benefit not only to Canada, a major producer and exporter of these crops, but on a larger scale as well, as legume crops are a staple in manycountries. Sulfur acid biosynthesis and accumulation is under complex metabolic control. The increased understanding, both of the enzymes involved and of their transcriptional and post-translational regulation, will lead to the development of crop plants with improved nutritional characteristics. |
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4. Homocysteine metabolism
The medical applications of our research relate to homocysteine, an intermediate of methionine metabolism that has been recognized as an independent risk factor for heart disease. Homocysteine levels in the blood are usually in the low-micromolar range. However, even a moderate increase in the plasma concentration of homocysteine, resulting from a variety of genetic, dietary, environmental, and drug-induced conditions, is associated with an increased risk of arteriosclerosis in humans. According to the most recent (1999) statistics from Health Canada , cardiovascular disease (CVD) is the leading cause of death amongst Canadians, accounting for 36% of all deaths. Homocystinuria is an autosomal, recessive disease characterized by elevated plasma homocysteine levels. The most common cause of this disease in humans is deficiency of the enzyme cystathionine beta-synthase. Cystathionine beta-synthase may also be linked to Down syndrome. The elucidation of the complex and interlocking mechanisms of cystathionine beta-synthase regulation and the underlying mechanisms of homocystinuria-associated mutations will lead to the design of therapeutic treatments for those at risk for atherosclerosis and to prevent the clinical manifestations of homocystinuria and Down syndrome. |
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