Purification and Use of Glycomacropeptide for Nutritional Management of Phenylketonuria

Abstract

Individuals with phenylketonuria (PKU) cannot metabolize phenylalanine (Phe) and must adhere to a low-Phe diet in which most dietary protein is provided by a Phe-free amino acid formula. Glycomacropeptide (GMP) is the only naturally occurring protein that does not contain Phe, and is of interest as a source of protein for dietary management of PKU. However, commercially available GMP contains too much Phe from residual whey proteins and does not contain adequate levels of all the indispensable amino acids to provide a nutritionally complete protein. The aim of this study was to increase purity of GMP and develop a mass balance calculation for indispensable amino acid supplementation of GMP foods. Cation exchange chromatography, ultrafiltration/diafiltration, and lyophilization were used at the pilot plant scale to decrease Phe. Enough purified GMP (5 kg) was manufactured to provide 15 PKU subjects with a 4-d diet in which the majority of protein was from GMP foods. A mass balance was used to supplement GMP foods so that all indispensable amino acids met or exceeded the daily recommended intake. GMP foods were tested in a human clinical trial as a replacement for the traditional amino acid formula. Nutritionally complete GMP foods created with high purity GMP provide individuals with PKU with more options to manage PKU, which may lead to improved compliance and quality of life.

Application of the response surface methodology for optimization of whey protein partitioning in PEG/phosphate aqueous two-phase system

“…Enriched ␣-lactoalbumin (␣-la) fractions may be used as ingredients for infants or in hypoallergenic food formulations, while enriched glycomacropeptide (Gmp) fractions may be used in diets for patients suffering from hepatic diseases or phenylketonuria [1][2][3]. ␤-Lactoglobulin (␤-lg) has excellent heat-and cold-set gelation characteristics as well as an excellent amino acids profile.…”

Glycomacropeptide, a low-phenylalanine protein isolated from cheese whey, supports growth and attenuates metabolic stress in the murine model of phenylketonuria

“…Glycomacropeptide (GMP), the only known naturally occurring dietary protein that, in its pure form, contains no phe (25), provides a new nutritional paradigm for PKU. Our studies in the murine model of PAH deficiency, the Pah enu2 mouse (PKU mouse) (32,39), which mimics the phenotype of human PKU, including elevated phe concentrations and cognitive defects, indicate that a GMP diet reduces phe concentrations in plasma and brain compared with an AA diet (39).…”

“…For commercial use, GMP is obtained from cheese making when -casein is cleaved by rennet chymosin into para--casein, which remains with the cheese curd, and GMP, which remains with the whey (8,17). GMP, the third most abundant protein in cheese whey, is highly polar, with an isoelectric point below 3.8, and is glycosylated by galactosamine, galactose, and -sialic acid at threonine sites (25). Moreover, GMP has a unique AA profile, including an absence of aromatic AA, phe, tryptophan, and tyrosine, as well as arginine, cysteine, and histidine, and concentrations of isoleucine and threonine that are two-to threefold greater, respectively, than those found in other dietary proteins (17).…”

Whey-ing up the options – Yesterday, today and tomorrow

“…Page 17 of 54 of whey protein solids in renneted cheese whey, has also been isolated using a combination of 376 chromatographic and membrane techniques (Holland et al, 2010;LaClair et al, 2009). …”

“…PKU)(LaClair et al, 2009;Ney et al, 2009).While much of the focus on whey utilisation over the past 30 years has been on the 406 proteins, lactose (the major whey solid) has also received attention, both in terms of improved isolation procedures, and applications for this carbohydrate and its derivatives (seeGaenzle et 408 al., 2007 and Hourigan et al, 2013 for reviews). Much of the attention has been on exploiting the physico-chemical properties of lactose in (i) designing and implementing improved 410 isolation techniques for higher purity lactose destined for baby food and drug excipient applications(Durham et al, 2004; Gaenzle et al, 2007; Hourigan et al, 2013); (ii) approaches 412 to the effective hydrolysis of lactose into the constituent monosaccharides(Gaenzle et al, 2007; Hourigan et al, 2013); and (iii) transformation of lactose into high value derivatives, such 414 as galacto-oligosaccharides as prebiotics(Fischer & Kleinschmidt, 2014; Splechtna et al, 2006).…”