The Role of Potassium in Betaine-Homocysteine Methyltransferase

Tryon, Katherine R.

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https://hdl.handle.net/2142/14766 Copy

Description

Title

The Role of Potassium in Betaine-Homocysteine Methyltransferase

Author(s)

Tryon, Katherine R.

Issue Date

2010-01-06T17:50:14Z

Director of Research (if dissertation) or Advisor (if thesis)

Garrow, Timothy A.

Doctoral Committee Chair(s)

Garrow, Timothy A.

Department of Study

Food Science & Human Nutrition

Discipline

Food Science & Human Nutrition

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

M.S.

Degree Level

Thesis

Keyword(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 Recently, unpublished crystallography pictures have shown a potassium ion that is interacting with some of the residues of BHMT that are involved in Hcy- and betaine-binding.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.

Graduation Semester

2009-12

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http://hdl.handle.net/2142/14766

Copyright and License Information

Copyright 2009 Katherine R. Tryon

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