Isolation and purification of κ-casein glycomacropeptide: A review

Bovine glycomacropeptide (GMP), present in cheese whey, is a glycan-phosphopeptide complex released from κ-casein by the action of chymosin during cheese making. Because GMP lacks phenylalanine and tyrosine, it is considered a potential dietary source of amino acids for patients with phenylketonuria or tyrosinaemia type I - genetic disorders affecting phenylalanine and tyrosine metabolism, respectively. The development of methods to obtain high-purity GMP remains a long-standing challenge in the dairy industry. This review discusses isolation and purification techniques suitable for producing GMP for dietary management of these disorders. Ultrafiltration (or dialysis) and deproteinization are widely used to remove non-GMP components from whey prior to chromatographic separation. Among chromatographic methods, anion exchange chromatography is regarded as the most versatile for selectively adsorbing GMP. Laboratory-scale purification yielding GMP with undetectable levels of contaminating amino acids can be achieved by a combined method with dialysis, deproteinization and anion exchange techniques. In our laboratory, bovine whey protein concentrate prepared by dialysis and commercial whey protein isolate were used as starting materials. Each sample was deproteinized by heat and acid treatments to obtain the soluble whey fraction, which was subsequently fractionated by anion exchange chromatography (or its batch method) to recover GMP free of detectable phenylalanine and tyrosine - making it applicable to the dietary treatment of the above-mentioned disorders. Future research should investigate GMP in 'second cheese whey', an industrial by-product from the manufacture of whey cheeses (e.g., Ricotta). Another challenge is developing large-scale GMP production methods using inexpensive, food-grade anion exchangers (e.g., chitin).