Amino Acid and Protein Digestion

Protein Digestion

Amino acids are ingested as proteins and peptides.

• Proteins and peptides are hydrolysed in the stomach and duodenum by gastric and pancreatic enzymes.

• Dipeptides and amino acids are absorbed through specific absorptive intestinal mucosal transport systems.

• There is metabolism of dipeptides and amino acids within the enterocyte.

• Specific transport systems carry amino acids and peptides across the cell basal membrane to the body, and are different from those on the luminal side of the intestine,.

• Minute amounts of intact protein may be absorbed particularly in the infant.


The dietary protein intake is approximately 70–100 g/day, with approximately 50–60% of animal origin. In addition, 20–30 g of endogenous proteins, 30 g of desquamated cells and 1–2 g plasma proteins (1–2 g as albumin), enzymes and mucoproteins are secreted into the intestine. Protein of endogenous origin is in general digested and absorbed more slowly than exogenous protein. The faecal excretion of protein-derived nitrogen is about 10 g/day or less, demonstrating an effective absorption of protein, which is of the order of 95% in the small intestine. This efficiency varies with the protein, for example the absorption of cooked haricot bean protein is poor. Faecal protein is largely bacterial in origin, whereas faecal nitrogen is of endogenous origin.

Protein absorption involves the breakdown of protein to tripeptides, dipeptides and amino acids. The site of maximal peptide or amino acid absorption may differ along the intestine and is species-dependent. The electrical gradient across the brush border is steeper in the jejunum than in the ileum. While most ingested protein is absorbed in the jejunum, some protein being absorbed in the ileum and some, albeit a small amount, passes on to the colon. Following a protein-containing meal there appear to be more intraluminal amino acids in the ileum than in the jejunum, suggesting that peptidases enter the ileal lumen. Absorption of amino acids from the ileum in humans may be more important than peptide absorption. The colonic mucosa appears to be an effective absorber of amino acids. Nitrogen absorption from the colon consists of the fermentation products of bacterial metabolism. It is only possible to guess at how much of the protein entering the colon is of exogenous origin and how much is endogenous. It is possible that 3–24 g of protein passes into the colon each day and of this, 40–60% is endogenous.

1. Protein absorption involves the breakdown of protein to tripeptides, dipeptides and amino acids. The site of maximal peptide or amino acid absorption may differ along the intestine.

2. Most ingested protein is absorbed in the jejunum, some is absorbed in the ileum and a small amount in the colon.

3. There are six phases in the digestion and absorption of proteins: (i) whole protein absorption; (ii) intraluminal digestion of protein and its breakdown products polypeptides, resulting from the sequential actions of the proteolytic enzymes of the stomach and pancreas; (iii) cellular uptake of amino acids and peptides; (iv) brush border digestion of small peptides; (v) intracellular metabolism; and (vi) transfer of amino acids and dipeptides from the intestinal cell to the blood stream.

4. Protein digestion begins in the stomach with the enzyme pepsin in the presence of hydrochloric acid. The next phase is the activation of proteolytic enzymes, a process initiated by enterokinase which converts the precursor trypsinogen to trypsin by the cleavage of a small terminal peptide. Some proteins are resistant to hydrolysis with the result that their subsequent absorption is incomplete. Whole protein absorption may be significant in newborn animals. This is of immunological importance. Proteolytic enzymes develop rapidly in the newborn.

5. Proteins are absorbed from the intestinal lumen largely in the form of small peptides and amino acids. Small quantities of whole proteins are also absorbed and enter the circulation in trace amounts. Intraluminal digestion of protein produces a mixture of small peptides and amino acids in which peptides predominate. The absorption of peptides and amino acids are complementary processes.

6. Free amino acids are transported into the absorptive cells by a number of well-defined mechanisms which are mainly active and Na+-linked. Several absorption mechanisms have defined specificity for certain groups of amino acids with structural features in common.

7. Active transport is a major mechanism of transmembrane transport of peptides. Active transport is limited to di- and tripeptides. Peptide transport by the PepT1 transporter is stereospecific, preferring peptides containing only l-amino acids or glycine. d-isomers appear to utilise the same transport systems as their comparable l-form but with reduced affinity characteristics. The transporter is unusual in having protons as the co-transporter. The stimulation of the gene is in part specific amino acid and dipetide dependent.

8. The majority of the peptidases of the intestinal mucosa are aminopeptidases, hydrolysing peptides sequentially from the amino-terminal end of the molecule.

9. The synthetic activity of the small intestinal mucosa is intense, requiring absorbed amino acids for rapid cell renewal, enzyme production, secretion of mucus and synthesis of apolipoproteins essential for chylomicrons.

10. There is active transport of amino acids through the basolateral membrane by transport systems which are Na+-independent and probably mediated by facilitated diffusion.

B) Amino Acid metabolism

Amino acids can be classified as essential or nonessential. An essential amino acid is one that has to be supplied in the diet in order to maintain a positive nitrogen balance.

Fewer than half of the protein amino acids can be synthesised by de novo pathways. The remainder must be supplied by nutrients.

The liver is important in protein synthesis, the non essential amino acids ( alanine, glycine, glutamic acid and glutamine) are normally present in many times greater amounts in the liver than in the plasma whereas the concentrations of the essential amino acids are the same in liver and plasma.

Essential Non-essential
Isoleucine Alanine
Leucine Arginine
Lysine Asparagine
Methionine Aspartate
Phenylalanine Cysteine
Threonine Glutamate
Tryptophan Glutamine
Valine Glycine

1. Dietary amino acids are either essential or non-essential. Non-essential amino acids can be synthesised from key intermediates in the glycolytic pathway, pentose phosphate pathway or the TCA cycle. Some amino acids may become essential under stress, eg glutamine, or lack of precursor eg tyrosine.

2. The synthesis of amino acids involves transamination or ammonia fixation. The a -amino group is generally derived from the amino groups of l-glutamate.

3. The catabolism of dietary proteins yields amino acids for recycling. Other sources of amino acids for catabolism include storage proteins and the metabolic turnover of endogenous proteins.

4. Protein catabolism involves the hydrolysis of covalent peptide linkages. The degradation of amino acids requires the removal of the a -amino nitrogen through deamination in the form of transamination or oxidative deamination. Transamination is the donation of the amino group to a -ketoglutarate, which is then regenerated by oxidative deamination.

5. There is a close link between the deamination products of amino acids and the TCA cycle. Amino acids directly converted to acetyl-CoA are ketogenic, but deamination products directly entering the TCA cycle are glucogenic.

6. The malate shuttle is important in maintaining a required balance between NAD and NADH across the mitochondrial membrane. This involves NAD-linked enzymes and the movement of aspartate and malate across the mitochondrial membrane, producing oxaloacetate on either side; the process is then repeated.

7. The transaminase alanine aminotransferase reaction allows the transportation of nitrogen from muscle to liver in the form of alanine.

8. Amino acid catabolic enzymes are under hormonal and dietary control.

9. Glutamine, while being a non-essential amino acid, is important as the most abundant free amino acid. It is an obligatory fuel for intestinal and immune cells, has a role in acid-base balance, provides a -amino groupings for renal ammoniagenesis, and is a precursor in nucleic acid biosynthesis.

10. The end-products of nitrogen catabolism are ammonia and urea. Ammonia is toxic and is carried to the liver as glutamine. Muscle transports ammonia to the liver in the form of alanine.

11. In the urea cycle, urea is produced by the sequential removal of nitrogen atoms. Urea production varies as a function of dietary protein intake, being reduced in starvation.


Nerve cells are the basic units of the nervous system which incorporates the brain, spinal cord and nerves. Nerves in the periphery may be motor or sensory, that is, stimulating or transmitting information to organs or tissues. A nerve cell receives, conducts and transmits signals over large distances. Though nerve cells are made in a wide variety of forms, the form of the signal is always the same: changes in the electrical potential across the nerve cells’ plasma membrane.

1. Nerve cells, regardless of anatomy or function, signal to each other from one synapse to another using chemical neurotransmitters, thus inducing an action potential.

2. The signals are received at voltage-gated channel receptors.

3. There are both excitatory and inhibitory neurotransmitters, which include amino acids.

4. Nitric oxide, which is widely distributed throughout the body and has many functions, is a rapidly acting neurotransmitter derived enzymatically from arginine.

Further Reading

Boger RH , Bode-Boger SM ( 2001) The clinical pharmacology of L-arginine. Annual Review of Pharmacology and Toxicology 41, 79-100.
Con PJ, Pin J-P ( 1997) Pharmacology and functions of metabotropic glutamate receptors. . Annual Review of Pharmacology and Toxicology 37, 205-238
Corringer P-J, Le Novere N, Changeuex J-P ( 2000) Nicotinic receptors at the amino acid level. . Annual Review of Pharmacology and Toxicology 40, 431-458
Davis KL, Martin E, Turko IV, Murad F ( 2001). Novel effects of nitric oxide . Annual Review of Pharmacology and Toxicology 41, 203-236.
Edmunds, B., Gibb, A.J. and Colquhon, D. (1995) Mechanisms of activation of glutamate receptors. Annual Review of Physiology57, 495–519.
Garthwaite, J. (1991) Glutamate, nitric oxide and cell-cell signalling in the nervous system. Trends in Neurological Sciences14, 60–7.
Gross SS ( 2001) Targetted delivery of nitric oxide Nature 409, 577-8.
Liebman SW ( 2001) The shape of a species barrier 410, 161-2
Myers SJ, Dingledine R, Borges K ( 1999) Genetic regulation of glutamte receptor ion channels . Annual Review of Pharmacology and Toxicology 39, 221-242.
Nitric Oxide Special Topic ( 1995) Nitric oxide Annual Review Physiology.57, 659-790
Stuehr DJ ( 1997) Structure function aspects in the nitric oxid synthases. Annual Review of Pharmacology and Toxicology 37, 339-360.
Vallance P ( 2001) Importance of asymmetrical dimethylarginine in cardiovascular risk Lancet 358, 2096-2097.


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