Protein digestion and absorption !

Mechanism
Exam priority: medium

Proteins are cut in the stomach and duodenum down to amino acids and short peptides, which the gut absorbs with its own transporters.

Updated 2026-11-01

Also called: Proteases, PepT1

See it in 3D: Stomach · Pancreas · Duodenum · Jejunum

Key points

Pepsin (from chief cells; pepsinogen is activated at pH < 3) provides only ≈10–20% of digestion; without it protein digestion is still nearly normal.
The main work is done by pancreatic proteases: endopeptidases (trypsin, chymotrypsin, elastase) and exopeptidases (carboxypeptidases A and B).
Brush-border aminopeptidases and dipeptidases act next.
Di- and tripeptides are absorbed by PepT1 (co-transport with H⁺) faster than free amino acids; most are hydrolysed inside the enterocyte.
Amino acids use different transporter families (neutral, basic, acidic, imino acids); a defect in one family affects gut and kidney at the same time.
Hartnup: the neutral amino acid transporter fails → tryptophan deficiency and pellagra-like symptoms. Cystinuria: the cystine, ornithine, lysine and arginine transporter fails → cystine stones.

What it is

Protein digestion begins in the stomach with pepsin and is completed by pancreatic proteases and brush-border peptidases. The enterocyte absorbs free amino acids through several Na⁺-dependent co-transporters, and also dipeptides and tripeptides through H⁺-coupled PepT1; inside the cell the peptides are finished off. Amino acids reach the liver via the portal vein.

Key facts

Endogenous proteins (enzymes, shed cells) add up to as much as dietary protein and are digested the same way.
In the newborn, a small amount of intact protein (antibodies in breast milk) can cross the mucosa.
Glutamine is the enterocyte's main fuel.

How it works, step by step

In the stomach, HCl denatures proteins and activates pepsinogen to pepsin.
Pepsin cuts internal bonds and yields polypeptides; it is inactivated when chyme is neutralized in the duodenum.
Enteropeptidase activates trypsin, which activates the rest of the pancreatic proteases.
Endopeptidases cut within the chain, and carboxypeptidases release amino acids from the C-terminal end.
Brush-border aminopeptidases and dipeptidases leave amino acids, dipeptides and tripeptides.
Amino acids enter with Na⁺ (or by exchange) and short peptides enter with H⁺ via PepT1.
Cytosolic peptidases complete hydrolysis; amino acids leave across the basolateral membrane into portal blood.

Clinical notes

Pancreatic insufficiency: creatorrhea (undigested meat fibres in stool) alongside steatorrhea.
Kwashiorkor: protein deficiency with relatively preserved calories → edema from low albumin and fatty liver.
Hartnup: neutral aminoaciduria, photosensitive dermatitis and ataxia, which improve with dietary niacin.
Protein-losing enteropathies cause hypoalbuminemia even when absorption is normal.

Test yourself

Think of the answer, then tap the question to see it.

Why does a total gastrectomy not prevent protein digestion, while pancreatic insufficiency does?

Pepsin contributes only a small share and pancreatic proteases can do all the work. Without pancreatic enzymes, however, protein passes nearly undigested.

What advantage does short-peptide absorption via PepT1 offer?

It is faster and more efficient than free amino acid uptake, and it preserves absorption when a specific amino acid transporter fails, as in Hartnup disease or cystinuria.

Why can Hartnup disease look like pellagra?

The defective neutral amino acid transporter absorbs tryptophan poorly in the gut and fails to reabsorb it in the kidney; with less tryptophan, less niacin is made.

What links cystinuria to intestinal amino acid absorption?

The same transporter for dibasic amino acids and cystine sits in the gut and the proximal tubule; its defect causes urinary loss of cystine, which precipitates into stones.

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See it in 3D

The structures of Durgical's 3D anatomy where it happens.

In Biochemistry

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Educational physiology content; not a diagnostic or treatment guide and no substitute for a health professional's advice. Values are approximate references. No doses are given.

Sources: 23.7 Chemical Digestion and Absorption: A Closer Look (OpenStax (Rice University), 2022); Hartnup disease: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2024); Chronic Pancreatitis (StatPearls (NCBI Bookshelf), 2024); Hall JE. Guyton and Hall Textbook of Medical Physiology, 13th ed. (ch. 66). Reference book used to check facts; its text and figures are not reproduced (Elsevier, 2016).

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Representative model, for educational purposes only.