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Robert Rej, Commentary, Clinical Chemistry, Volume 61, Issue 10, 1 October 2015, Page 1245, https://doi.org/10.1373/clinchem.2015.238253
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This case, with seemingly erratic serum AST activities over time, must have been perplexing to follow. Lack of agreement of results from different laboratories, 2 ostensibly using the same method, presented additional layers of complexity.
IFCC reference methods for enzymes have had a profound effect on harmonization; manufacturers have used them both for calibration and as the basis for conditions of assay. Unfortunately, addition of exogenous pyridoxal phosphate (PLP) seems to have been largely considered as an “option” for aminotransferases. The reasons for this are complex and historical. The original procedures omitted this essential cofactor because the authors were unable to show measurable effect of exogenous PLP on serum AST. Unfortunately, the phosphate buffer used in assays for aminotransferases until the mid-1970s inhibited binding of PLP to any apo-enzyme present, likely by competing for the phosphate-binding site (1).
In addition, increases in catalytic activity found with addition of coenzyme, even in the absence of phosphate, are typically modest because apo-aminotransferases are far less stable than their holoenzyme counterparts and may undergo changes in tertiary structure, preventing reformation of holoenzyme even when the cofactor is reintroduced. Perhaps the immunoglobulin-bound AST imparts additional stability for the apo-AST, which might normally lose aspects of its tertiary structure as would occur with the nonbound form.
