Protein digestion from mouth to anus. Visual, science-backed
How does protein digestion occur in the human body? In this post, I integrate visuals with text to explain how proteins are digested along your digestive tract, from mouth to anus.
Jump ahead to focus on what happens:
Or keep reading to dive into the details step by step!
I prepared this post just for you, with lots of visuals, to make the digestion process of protein simple to understand and easier to remember while still accurate and precise!
This post is part of a series on the digestive system.
Table of content
How proteins are broken down
Proteins are chains of hundreds or thousands of amino acids . Shorter chains of amino acids are called polypeptides. And, very short chains are called dipeptides , tripeptides , etc.1.
A simple chain of amino acids is the first structural level of a protein . It is hence called the primary protein structure. Within a chain, amino acids are linked to one another by strong linkages, called peptide bonds1 .
For a protein to be functional in a living being, the chain of amino acids needs to have a specific shape. The chain is hence folded at a secondary and even a tertiary level . This shape is maintained by other kinds of bonds added to the chain, such as hydrogen bonds1 .
Our gut is only able to absorb small molecules: amino acids, di- and tripeptides. Hence, our digestive system needs to find out how to break down all these bonds so that amino acids can be separated from each other.
Hydrogen bonds can be broken down by strong acidity. Peptide bonds, in contrast, are broken down by specific enzymes called proteases or proteolytic enzymes1.
Protein breakdown — wrap up:
Proteins are chains of amino acids folded into 3D structures . Protein structure is maintained thanks to different kinds of bonds, mainly peptide , and hydrogen bonds . The digestion process breaks down these linkages, converting large proteins into free amino acids .
But how does this process happen, step by step?
Protein digestion begins in the mouth
In the mouth, although no chemical digestion of protein happens, a significant action of mechanical breakdown takes place.
No chemical digestion of protein occurs in the mouth
Saliva does contain enzymes, including proteases called kallikreins. But these proteases are not directly involved in the digestion process of protein. Instead, they play a role in regulating the blood flow in the salivary glands2.
Mechanical digestion: mastication and mixing
The first step in protein digestion starts with a strong mechanical break down in the mouth.
Bitting with your incisor teeth, crushing with your molars, and mixing food particles and saliva with your tongue2.
This mechanical digestion separates the chunks of food into smaller and smaller fragments.
It does not affect the molecular structure of the proteins, though.
If protein structure is not affected, why are mastication and mixing important?
Because small fragments coated with saliva are easily moved down by the esophagus, the stomach processes them more efficiently, and their surface area in contact with enzymes is much greater2.
Well chewed proteins will be digested much more easily in the digestive tract, as opposed to big chunks of entangled proteins, whose peptide bonds are difficult to reach by enzymes.
This mechanical action of chewing and mixing with the tongue creates a mixture called the bolus, which you propel to the esophagus when swallowing.
In the mouth — wrap up:
Although some proteases are secreted in the saliva, they don’t act in protein digestion. Yet, digestion starts in the mouth, with a strong mechanical action of chewing and mixing. Well chewed food significantly facilitates the digestion of proteins in the stomach.
The process of protein digestion in the stomach
After arriving into the stomach from the esophagus, the bolus is slowly mixed with gastric juice, creating a mixture called chyme. The strong acidity of the chyme , the presence of the proteolytic enzyme pepsin , and the constant churning create ideal conditions to start protein digestion.
Chemical digestion: hydrochloric acid and pepsin
The walls of the stomach contain small indentations, called gastric pits. These gastric pits hide tubular glands secreting a digestive juice — the gastric juice — into the stomach.
Gastric juice contains hydrochloric acid (HCl)
Hydrochloric acid is secreted as hydrogen ions and chloride ions by the parietal cells in the gastric glands2–4. This rise of hydrogen ion concentration strengthens the acidity of the chyme till about pH 23,5.
Under such a strong acidity, proteins start to denature, meaning that they begin to lose their 3D structure. This is because acidity disrupts the weak hydrogen bonds that maintain the protein folded1.
At this stage, however, amino acid chains are still intact, as pH does not break the strong peptide bonds between amino acids (most of the time)1.
But, this unfolding already makes protein much more vulnerable to protease attacks !
Gastric juice contains pepsin
Precisely, gastric juice also contains a protein digestion enzyme called pepsin . At first, pepsin is inactive. The chief cells of the gastric pits secrete its inactive precursor pepsinogen .
At a pH below 6, however, pepsinogen is converted into pepsin.
How does this activation occur?
In presence of hydrogen ions , pepsinogen , which is also a protein, loses a short peptide and becomes the active pepsin .
Mechanical digestion: churning and grinding
The continuous movements of the stomach walls help the chemical actions of hydrogen ions and pepsin.
Slow waves of contraction, called peristalsis, go from the top to the bottom of the stomach at a speed of about 1 cm per second2.
At the top of the stomach, this wave of contractions has a churning effect. It mixes the bolus with gastric juice, creating the chyme. This allows hydrogen ions and pepsin to diffuse evenly and breakdown proteins2.
On its lower side, the stomach is narrower while its muscular walls are thicker. Hence, approaching the bottom of the stomach, the contraction wave starts to have a strong grinding effect. This fragments even more the remaining chunks that were not completely chewed2.
Eventually, when the contraction wave reaches the bottom of the stomach, a last strong contraction releases a small spurt of chyme into the small intestine while pushing the rest of the chyme backward for further churning and grinding. This way, a small amount of chyme is discharged to your small intestine at the end of each wave, periodically2,3.
In the stomach — wrap up:
By combining very low pH with a digestion protein enzyme and churning, the stomach efficiently starts the chemical process of protein digestion. Yet, only 10-20% of protein digestion occurs in the stomach itself, leaving most of the protein breakdown work to the small intestine…
The process of protein digestion in the small intestine
Projected by the stomach, the chyme arrives in the first segment of the small intestine — the duodenum — with partially digested proteins and polypeptides. Again, the combination of chemical and mechanical actions will continue the work of protein digestion.
Chemical digestion: pancreatic proteases and brush border peptidases
In the duodenum, the pancreatic juice is released.
Pancreatic juice contains bicarbonate (HCO3-)
This neutralizes the acidity of the arriving chyme, preventing it from damaging the lining of the intestine3.
Besides, the pepsin enzyme , being also a protein, is sensitive to pH. At pH 5 and above, pepsin activity stops. And by the time when pH reaches 6.5, our poor pepsin even starts to denature8.
So, if our famous stomach protease inactivates upon arrival into the small intestine, who will keep digesting proteins then?
Pancreatic juice contains powerful proteases
Here we are: the pancreatic juice also contains 4 main proteolytic enzymes secreted by the acinar cells of the pancreas4.
These proteases are much more powerful than pepsin. Hence, the greater part of protein digestion occurs here, in the duodenum and upper jejunum3, the first two segments of the small intestine.
- trypsinogen ,
- chymotrypsinogen ,
- proelastase , and
- procarboxypeptidase .
These precursors are converted into active enzymes through a little complex and quite interesting process! Let’s see how…
The small intestine also produces enzymes
The intestine is covered by very small finger-like structures called villi, themselves covered with epithelial cells called enterocytes. This multitude of villi on the intestine wall looks like a smooth brush, thence its name — the brush border2.
Then again, the membrane of enterocytes is shaped in even smaller finger-like structures called microvilli .
Among many functions, such as absorption of nutrients, the brush border also plays a role in digestion. Enterocytes of the duodenum and the jejunum secrete different kinds of proteases — enteropeptidases — also called enterokinases. They are anchored to the microvilli of the enterocytes membrane . As they are hooked to the membrane, they are referred to as brush border enzymes3.
So, how are our pancreatic enzymes activated?
Second , trypsin itself helps convert trypsinogen into trypsin!6
Third , trypsin converts:
- chymotrypsinogen into chymotrypsin ,
- proelastase into elastase , and
- procarboxypeptidase into carboxypeptidase3,6!
Once activated, trypsin, chymotrypsin, and elastase breakdown remaining proteins and polypeptides into even smaller polypeptide chains of 2 to 6 amino acids3.
Carboxypeptidase breaks further down some of these small polypeptides into individual amino acids3.
Finally, enteropeptidases break small peptides down to tri-, dipeptides, and amino acids3.
And here we are. Most proteins have been digested at this point, and absorption already happens from the duodenum.
Interestingly, enterocytes can absorb not only amino acids but also di- and tripeptides3.
Mechanical digestion: peristalsis and segmentation
As the chyme has been prepared by mastication and churning, it is already quite liquid with very small particles when reaching the small intestine. Thus, the mechanical movements in the small intestine have more of a mixing effect rather than a breakdown one.
Two main kinds of contractions happen in the small intestine: peristalsis and segmentation.
As in the stomach, some waves of contraction, called peristalsis, are moving the chyme along the small intestine2.
But sometimes, the small intestine contracts at different points and maintains its contraction for a while before relaxing and contracting again on adjacent segments2. This is segmentation.
Peristalsis and segmentation in the small intestine have several functions2:
- they mix the acidic chyme coming from the stomach with the alkaline pancreatic juice,
- they ease the mixing of food particles with pancreatic enzymes, and
- they help the absorption of already liberated amino acids, di- and tripeptides.
As most proteins are being digested in the small intestine, absorption of amino acids, di- and tripeptides already starts in the duodenum, along this same brush-border. This absorption continues in the next segments of the small intestine: jejunum and ileum.
In the small intestine — wrap up:
Most of the protein digestion process happens at the beginning of the small intestine, in the duodenum, and the upper jejunum. Proteins partially digested by the stomach are further broken down by several powerful pancreatic proteases and by enzymes hooked on the membrane of the intestinal epithelial cells. The protein digestion process finishes inside these epithelial cells.
Protein fermentation in the large intestine
Despite the thorough process of protein digestion started from the mouth, continued in the stomach, and mostly done in the small intestine, some proteins still reach the large intestine not totally digested3,4.
These proteins can come from the diet, like elastin and collagen; or from the digestive system itself, like sloughed epithelial cells, dead bacterias, or pancreatic enzymes, which are also proteins4.
After arriving in the large intestine, these proteins are further decomposed by colonic bacteria, mainly in the distal colon4. This degradation leads to the formation of useful molecules for our body, such as short-chain and branched-chain fatty acids.
Colonic epithelial cells absorb fatty acids4. In the body, they are used as nutriments, and some of them are locally used as an energy source by epithelial cells of the colon.
Frequently Asked Questions
I propose this FAQ section for readers who are looking for specific straight to the point answers.
If you have already read this post from the beginning till here, the following information will not bring much more to you.
Where does protein digestion begin and end?
Where does the chemical digestion of protein begin?
The chemical protein digestion begins in the stomach, with hydrochloric acid (HCl) and pepsin.
Hydrochloric acid denatures proteins, meaning that they lose their 3D shape and unfold1. By opening themselves this way, they start to be more vulnerable as their surface area in contact with enzymes increases2–4.
Learn more about chemical protein digestion in the stomach.
Where does protein digestion occur?
Protein digestion takes place all along the digestive tract.
In the mouth, proteins are separated into smaller and smaller particles by mechanical digestion. See how…
In the stomach starts the chemical digestion of proteins, through denaturation and breakdown. See how…
Overall, protein digestion mainly occurs in the small intestine, with most of the job done in the duodenum and upper jejunum, thanks to a series of pancreatic and intestinal protein digestion enzymes like trypsin3,6. See how…
In the large intestine, the last protein residues are fermented by colonic bacterias. See how…
Where is protein digestion completed?
Protein digestion is completed in the distal colon of the large intestine.
Learn more about protein fermentation in the large intestine.
If you want to dive deeper into the metabolic pathways behind gastric and pancreatic juices secretion and protein digestion, I recommend having a look at the Kyoto Encyclopedia of Genes and Genomes. It proposes an exhaustive pathway map along with other detailed information when you click on the different molecules.
Did you enjoy this post?
Then you will likely enjoy our newsletter where we share our latest posts and explorations! You will discover there our research and experiments on a variety of topics such as, gardening, crafting, health, spirituality, traveling, and more.
1. Nelson DL, Cox MM. Lehninger principles of biochemistry seventh edition. 2017.
2. Smith ME, Morton DG. The Digestive System: Systems of the Body Series. Oxford University Press for The Company of Biologists Limited; 2011.
3. Rogers K, others. The Digestive System. Oxford University Press for The Company of Biologists Limited; 2010.
4. Kanehisa M, Goto S. KEGG: Kyoto encyclopedia of genes and genomes. Nucleic acids research. 2000;28(1):27-30. https://www.genome.jp/kegg-bin/show_pathway?hsa04974.
5. Reynolds JC. The Netter Collection of Medical Illustrations: Digestive System: Part 1 - the Upper Digestive Tract E-Book. Elsevier Health Sciences; 2016.
6. Reynolds JC. The Netter Collection of Medical Illustrations: Digestive System: Part 2 - Lower Digestive Tract E-Book. Oxford University Press for The Company of Biologists Limited; 2016.
7. Johnson LR, others. Physiology of the gastrointestinal tract. 2012. https://www.worldcat.org/title/physiology-of-the-gastrointestinal-tract/oclc/789131658.
8. Piper D, Fenton BH. PH stability and activity curves of pepsin with special reference to their clinical importance. Gut. 1965;6(5):506. http://dx.doi.org/10.1136/gut.6.5.506.