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.

Figure 1

Amino acid pattern of DRI, adjusted target for human clinical trials, and protein composition of purified (not supplemented) GMP produced in the present study. Values are mean ± SD. Sample size was n = 10.

Figure 2

Amino acid profile of GMP strawberry pudding compared to amino acid formula (Phlexy-10 Drink Mix, SHS North America, Rockville, Md., U.S.A.) Values are mean ± SD. Sample size was n = 2. Same letter above GMP strawberry pudding and amino acid bars indicates that values are not statistically different (P > 0.05).