James' Unwanted Blood Clots

The laboratory report states that James has half the normal activity of antithrombin III.
The following pages illustrate how thrombin works and how antithrombin III inhibits it.

 

How antithrombin III inhibits thrombin (and several other clotting factors)

 

Antithrombin III contains a peptide loop that binds to the recognition site of thrombin. Thrombin cleaves the antithrombin III loop, but the cleaved antithrombin III fails to disengage from the thrombin. Antithrombin III is an example of a suicide inhibitor since both the antithrombin III and the thrombin are permanently inactivated.

As described in the next page, heparin, a carbohydrate that is present on cells that line blood vessels, is required for the antithrombin III-thrombin interaction.

 

The antithrombin III-heparin-thrombin complex.. Antithrombin III (peptide backbone outlined in pink) contains a loop (shown in red) that interacts with thrombin's recognition site (thrombin's heavy chain peptide backbone is shown in blue).

 

In addition to thrombin, antithrombin III also inhibits activated factors XIIa, XIa, IXa, and Xa.

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