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The Role of Potassium in Betaine-Homocysteine Methyltransferase

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Title: The Role of Potassium in Betaine-Homocysteine Methyltransferase
Author(s): Tryon, Katherine R.
Advisor(s): Garrow, Timothy A.
Contributor(s): Garrow, Timothy A.
Department / Program: Food Science & Human Nutrition
Discipline: Food Science & Human Nutrition
Degree Granting Institution: University of Illinois at Urbana-Champaign
Degree: M.S.
Genre: Thesis
Subject(s): Homocysteine Hyperhomocysteinemia BHMT Potassium coordination sphere
Abstract: Homocysteine (Hcy) is an intermediate of methionine metabolism and acts as a critical branch point between protein synthesis and numerous regulatory pathways in the cell. Elevated plasma total Hcy (tHcy) is associated with an increased risk for cardiovascular disease, although the mechanism by which this occurs remains unclear. Two enzymes are responsible for the remethylation of Hcy to methionine: methionine synthase and betaine-homocysteine methyltransferase (BHMT). Methionine synthase function depends on adequate availability of vitamin B12 and folate which links cardiovascular disease risk to nutritional status. The Hcy remethylation pathway through BHMT, however, requires only the substrate betaine which is derived from dietary or synthesized choline. Recently, unpublished crystallography pictures have shown a potassium ion that is interacting with some of the residues of BHMT that are involved in Hcy- and betaine-binding. These residues include Asp26 and Gly27, which along with Gly28 comprise an amino acid fingerprint that is common among Hcy S-methyltransferase proteins. All three residues of this DGG motif were substituted with a different amino acid (Asp26Ala, Gly27Ser and Gly28Ser) to examine the effect these residues have on BHMT activity, potassium-binding and substrate-binding kinetics. We demonstrate that these substitutions are directly responsible for decreases in Hcy binding, enzyme velocity and catalytic turnover. Mutations in the potassium coordination sphere appear to be more detrimental to BHMT function than changes to the other conserved residue.
Issue Date: 2010-01-06
URI: http://hdl.handle.net/2142/14766
Rights Information: Copyright 2009 Katherine R. Tryon
Date Available in IDEALS: 2010-01-06
2012-01-07
Date Deposited: December 2
 

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