Commentary

R. Rej
2015 Clinical Chemistry  
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
more » ... 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. AST activity measured without PLP supplementation is directly proportional to total serum AST but inversely proportional to the PLP saturation of that enzyme. With exogenous PLP, total AST is measured independent of vitamin-B 6 status and is more representative of the total enzyme in circulation. Paradoxically in this case, omission of PLP apparently resulted in preferential measurement of nonbound enzyme, presenting a less-complicated clinical picture. Several instances of macroenzymes, macro-AST in particular, have been reported in pregnancy (2 ). Other reports of macroenzymes are sufficiently numerous so that an isolated finding of a single abnormally increased enzyme activity in an otherwise unremarkable case should prompt one to "think macroenzyme."
doi:10.1373/clinchem.2015.238253 pmid:26416920 fatcat:pe4l2oob6fgs7duoabn5rwzppm