Nonprotein nitrogen and protein-derived peptides in human milk

Beyond proteins, milk contains an array of smaller nitrogen (N)-containing components generally referred to as nonprotein nitrogen (NPN). These include milk protein–derived peptides, peptide hormones, amino acids (AAs), N-containing oligosaccharides, N-containing monosaccharides, nucleic acids (DNA and RNA), free nucleotides, and small molecules, including urea, uric acid, ammonia, creatine, creatinine, carnitine, and polyamines. Human milk (HM) is unique in that NPN comprises up to 25% of the total N, compared to 5% in cow milk. Many of these milk components have functions in infants; for example, urea N can be used to synthesize nonessential AAs or converted by the gut microbiota as an N source. In addition, some milk protein–derived peptides have antimicrobial, antihypertensive, and other activities. This chapter reviews components of the NPN fraction of HM, their physiological relevance, typical amounts in milk, factors that affect their concentrations, the analytical techniques used to determine their concentrations, and areas for future research.