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Importance and Metabolism of Non Protein Nitrogen Compounds in Milk 


Urea is main constituent of NPN in human milk. About 0.18 mg/ml urea nitrogen is present, which is about 50% of total NPN. Cow’s milk contains about 0.08 mg/ml urea nitrogen.

  • Importance:-

The proportion of urea nitrogen utilized by the infant is dependent on its nitrogen requirement. It has been shown that term infants recovering from infection.

Low birthweight infants, who also have a high nitrogen requirement, were shown to retain about 28% of labeled urea nitrogen.

The retained urea nitrogen can also be utilized by intestinal microorganisms, serving as a substrate for protein and nucleic acid synthesis by the gut microflora—up to 7% of labeled urea nitrogen was found incorporated into fecal bacteria.

Part of urea is probably converted to ammonia by bacterial and mucosal enzymes and then metabolized by the infant.

  • Metabolism:-

Rumen microorganisms digest protein and produce ammonia. Excess ammonia crosses from the rumen into the bloodstream and is transported to the liver where it is converted to urea. The urea is then released into the bloodstream and is either excreted in urine or milk.

If the diet is deficient in nitrogen, then the urea is not excreted, but recycled back into the rumen and converted back to ammonia.



Carnitine is found in the milk of all species and its concentration does not appear to be affected by maternal diet.

  • Importance:-

Carnitine is essential for the transport of long chain fatty acid into mitochondria for oxidation.

It also transports the toxic compounds generated out of this cellular organelle to prevent their accumulation.

The amount of carnitine in human milk is about 1.5 mg N/liter.

Carnitine is concentrated in tissues like skeletal and cardiac muscle that utilize fatty acids as a dietary fuel.

  • Metabolism:-

Adults eating mixed diets that include red meat and other animal products obtain about 60–180 milligrams of carnitine per day. Vegans get considerably less (about 10–12 milligrams) since they avoid animal-derived foods. Most (54–86%) dietary carnitine is absorbed in the small intestine and enters the bloodstream.

The kidneys efficiently conserve carnitine, so even carnitine-poor diets have little impact on the body’s total carnitine content. Rather than being metabolized, excess carnitine is excreted in the urine as needed via the kidneys to maintain stable blood concentrations.


Unesterified choline have been found in human milk. About 3 to 9 mg N/liter of NPN is derived from unesterified choline. The concentration of choline is higher in early lactation than in mature milk.

  • Importance:-

Choline has not yet been defined as essential nutrient but it has been suggested that the premature may benefit from endogenous choline.

It is needed for neurotransmitter synthesis (acetylcholine), cell-membrane signaling (phospholipids), lipid transport (lipoproteins), and methyl-group metabolism (homocysteine reduction).

It is a basic constituent of lecithin.

  • Metabolism:-

Choline can be acquired from the diet and via de novo biosynthesis through the methylation of phosphatidylethanolamine (PE) to phosphatidylcholine (PC). However, de novo synthesis of choline alone is not sufficient to meet human requirements. However, de novo synthesis of choline alone is not sufficient to meet human requirements. Dietary choline from a variety of choline-containing foods is absorbed by the intestine and uptake is mediated by choline transporters. The major fate of choline is conversion to PC (also known as lecithin), which occurs in all nucleated cells. Upon entry into the cell, choline is immediately phosphorylated to phosphocholine, or oxidized to betaine in some cell types such as hepatocytes.


Creatine is a nitrogenous organic acid. About 0.1 g N/liter is present in milk.

  • Importance:-

Its main role is to facilitate recycling of adenosine triphosphate (ATP), the energy currency of the cell, primarily in muscle and brain tissue.

  • Metabolism:-

Creatine, which is synthesized in the liver and kidneys, is transported through the blood and taken up by tissues with high energy demands, such as the brain and skeletal muscle, through an active transport system.

During times of increased energy demands, the phosphagen (or ATP/PCr) system rapidly resynthesizes ATP from ADP with the use of phosphocreatine (PCr) through a reversible reaction with the enzyme creatine kinase.


Taurine is organic nitrogenous compounds that have been determine in human milk and milk of other animals. Taurine is most abundant in sheep, monkey and mouse milk.

  • Importance:-

Taurine has many fundamental biological roles, such as conjugation of bile acids, antioxidation, osmoregulation, membrane stabilization, and modulation of calcium signaling. It is essential for cardiovascular function, and development and function of skeletal muscle, the retina, and the central nervous system.

  • Metabolism:-

Mammalian taurine synthesis occurs in the pancreas via the cysteine sulfonic acid pathway. In this pathway, cysteine is first oxidized to its sulfinic acid, catalyzed by the enzyme cysteine dioxygenase. Cysteine sulfinic acid, in turn, is decarboxylated by sulfinoalanine decarboxylase to form hypotaurine. Hypotaurine is enzymatically oxidized to yield taurine by hypotaurine dehydrogenase.

Amino acids:-

A large proportion of our cells, muscles and tissue is made up of amino acids, meaning they carry out many important bodily functions. Milk contain 0.05 g N/liter of amino acids.

  • Importance:-

Protein synthesis.

Muscle building.

  • Metabolism:-

Dietary amino acids can be consumed as free amino acids or, more often, they are acquired from digested dietary proteins that are hydrolyzed through the concerted actions of gastric and pancreatic peptidases. Dietary protein digestion begins in the stomach via the actions of the pepsins, and continues within the lumen of the duodenum. Within the small intestine there are two principal pancreatic enzymes involved in protein digestion; trypsin and chymotrypsin. Several additional pancreatic peptidases play a lesser role in peptide digestion and include the carboxypeptidases and elastin.

Orotic acid:-

Orotic acid is a heterocyclic compound and an acid. It is also known as vitamin B13.

  • Importance:-

An intermediate in pyrimidine metabolism. Orotic acid (OA), a naturally occurring substance, is a key intermediate in the biosynthetic pathway of pyrimidines. Orotic acid can partially compensate for B12 deficiency.

  • Metabolism:-

Carbamoyl phosphate, which accumulates within hepatic mitochondria in patients with ornithine transcarbamoylase deficiency, can diffuse to the cytosol and enter the pyrimidine pathway, resulting in greatly increased orotic acid production and excretion.

Creatinine, uric acid and ammonia:-

The presence of creatinine, creatine, uric acid, and ammonia in human milk has been well documented the amount of nitrogen provided from all these compounds together is very low and their contribution to the total NPN fraction in human milk is minor. There have been no indications of any physiological significance of these compounds provided from the diet.


The NPN fraction of human milk contains many compounds of diverse chemical composition. Several of these, like some peptide hormones and nucleotides, may act as growth factors, while others, like oligosaccharides and amino sugars, may influence the intestinal microflora. Other compounds, such as urea, may be of little significance for the healthy term infant but could be of importance as a nitrogen source for the compromised infant.

  • https://www.nestlenutrition-institute.org/docs/default-source/global-dcoument-library/publications/secured/881688262da4f2f175f72c4f110412ce.pdf?sfvrsn=0.
  • https://www.ncbi.nlm.nih.gov/pubmed/3651516.
  • https://www.vitamins-supplements.org/orotic-acid.php


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