What is the mechanism for the absorption of amino acids in the ileum?

November 18, 2025 •

4 min read

While protein digestion begins in the stomach and duodenum, the bulk of nutrient uptake, including amino acids, happens in the small intestine, which comprises the ileum. This highly efficient and complex process ensures the body receives the building blocks it needs, relying on specialized transporter proteins embedded within the intestinal cell membranes.

Quick Summary

The ileum absorbs amino acids via a complex transcellular process involving sodium-dependent co-transporters for single amino acids and proton-dependent transporters for small peptides.

Key Points

Sodium-Dependent Co-Transport: Free amino acids are absorbed by specialized carrier proteins that move them into intestinal cells alongside sodium ions, relying on a sodium gradient.
ATP-Fueled Gradient: The necessary sodium gradient is maintained by the sodium-potassium pump ($$Na^+/K^+$$-ATPase) on the basolateral membrane, making the entire process an active one.
Peptide Absorption via PepT1: Di- and tripeptides are absorbed through a separate, highly efficient, proton-dependent transporter called PepT1, which is often faster than free amino acid uptake.
Intracellular Peptide Hydrolysis: Once inside the enterocyte, absorbed di- and tripeptides are broken down into individual amino acids by cytoplasmic enzymes.
Basolateral Exit to Bloodstream: All absorbed amino acids exit the intestinal cell via different, primarily sodium-independent, transporters on the basolateral membrane to enter the portal circulation.
Distinct Transporter Specificities: Different sets of transporters exist for distinct categories of amino acids (e.g., neutral, acidic, basic, imino), though some overlap in function occurs.

Protein Digestion Precedes Absorption

Before amino acids can be absorbed, dietary proteins must be broken down into their constituent parts: free amino acids, dipeptides, and tripeptides. This process starts in the stomach with pepsin and continues in the small intestine with pancreatic enzymes like trypsin and chymotrypsin. The final stages of digestion occur at the brush border of intestinal epithelial cells (enterocytes), where membrane-bound peptidases complete the breakdown into absorbable units. Although most protein absorption occurs in the jejunum, the ileum efficiently handles any remaining nutrients, including specific amino acids and bile salts.

The Transcellular Absorption Pathway

Amino acid absorption in the ileum is primarily a transcellular process, meaning nutrients move across the enterocyte rather than between cells. This journey involves moving from the intestinal lumen, across the apical (luminal) membrane of the enterocyte, through the cytoplasm, and finally out across the basolateral (serosal) membrane into the interstitial fluid, before entering the portal circulation. The driving force for much of this process is an electrochemical gradient maintained by the sodium-potassium pump ($$Na^+/K^+$$-ATPase), located on the basolateral membrane. This pump actively transports sodium ions out of the cell, creating a low intracellular sodium concentration that powers the uptake of amino acids on the apical side.

Absorption of Free Amino Acids

The transport of free amino acids across the apical membrane is mediated by several distinct, sodium-dependent co-transporters, which vary based on the amino acid's chemical properties. This is a form of secondary active transport because it does not directly use ATP but relies on the sodium gradient created by the ATP-powered sodium-potassium pump. There are at least seven different sodium-dependent systems identified in the intestinal brush border, each with overlapping specificities for particular groups of amino acids.

Key Sodium-Dependent Transporter Systems

System B$^0$: This major transport system is responsible for the uptake of most neutral amino acids, including alanine, valine, and methionine. It is an electrogenic process, moving both a sodium ion and a neutral amino acid into the cell.
System A (SNAT2): Specializes in the transport of small, neutral amino acids such as alanine, proline, glycine, and glutamine.
EAAT Family (System X$^-$): Facilitates the transport of acidic amino acids like aspartate and glutamate, often coupled with sodium and a proton.
System b$^0$,+: This sodium-independent system, composed of a heterodimer, is responsible for the absorption of cationic amino acids (e.g., lysine, arginine) and cystine. It functions as an exchanger, moving these amino acids in while moving neutral amino acids out.
System IMINO (SIT1): Specifically transports imino acids like proline and hydroxyproline, requiring sodium and chloride.

Absorption of Di- and Tripeptides

Interestingly, the absorption of small peptides (dipeptides and tripeptides) is often more rapid and efficient than that of free amino acids. This is mediated by a distinct, high-capacity, proton-dependent transporter called PepT1.

PepT1 Transport: PepT1 transports a di- or tripeptide into the enterocyte along with a proton ($$H^+$$). The proton gradient is maintained by a separate sodium-proton exchanger on the apical membrane.
Intracellular Hydrolysis: Once inside the enterocyte, the vast majority of these peptides are hydrolyzed into single amino acids by cytoplasmic peptidases before being transported out of the cell.

Basolateral Membrane Transport

After accumulation within the enterocyte, the amino acids must be transported across the basolateral membrane to enter the portal bloodstream. This is primarily achieved through facilitated diffusion via a different set of transporters, which are mostly sodium-independent.

Examples of Basolateral Transporters: Systems like LAT2 (SLC7A8) and y+LAT2 (SLC7A7) are involved in this step, mediating the exit of amino acids into the circulation.

Comparison of Amino Acid and Peptide Absorption


Feature	Free Amino Acid Absorption	Peptide (Di- & Tripeptide) Absorption
Mechanism	Secondary active transport (sodium-dependent co-transport)	Secondary active transport (proton-dependent co-transport via PepT1)
Transport Efficiency	Can be subject to competitive inhibition among amino acids that share transporters.	Often more rapid and efficient than free amino acid transport.
Energy Source	Indirectly dependent on the ATP-driven sodium-potassium pump.	Indirectly dependent on the proton gradient, which is linked to a sodium-proton exchanger.
Intracellular fate	Directly crosses the basolateral membrane into the bloodstream.	Hydrolyzed into free amino acids by intracellular peptidases before crossing the basolateral membrane.
Transporter Type	Diverse, substrate-specific sodium-dependent transporters (e.g., B$^0$AT1, EAAT3).	Predominantly via the single high-capacity PepT1 transporter.

Conclusion: A Multi-System Process

In conclusion, the mechanism for the absorption of amino acids in the ileum is a highly coordinated and complex process that goes beyond simple diffusion. It involves a sophisticated transcellular pathway utilizing multiple specialized transport systems. Free amino acids are primarily taken up via sodium-dependent co-transport, while di- and tripeptides are absorbed with protons via the high-capacity PepT1 transporter. The entire process is energetically driven by the sodium-potassium pump on the basolateral membrane. These absorbed nutrients are then released into the portal circulation to be distributed throughout the body. This dual-pathway approach ensures maximum absorption efficiency and nutritional uptake. Defects in these transport systems, though rare, can have serious nutritional consequences, highlighting the importance of this intricate physiological process.

For a deeper look into the intricate world of amino acid transport, this review from the National Institutes of Health provides an overview of various transporters and their functions within the body: Role of amino acid transporters in amino acid sensing.

Frequently Asked Questions

Yes, while the movement of some amino acids is technically facilitated diffusion (passive), the overall absorption process is considered active transport because it is dependent on the sodium gradient maintained by the energy-intensive sodium-potassium pump.

The sodium-potassium pump, located on the basolateral membrane of enterocytes, actively pumps sodium out of the cell. This creates a low intracellular sodium concentration, which in turn drives sodium-dependent co-transporters on the apical membrane to pull amino acids into the cell.

No, they are absorbed via distinct mechanisms. Single amino acids use sodium-dependent co-transporters, while di- and tripeptides are absorbed by the proton-dependent PepT1 transporter.

Once inside the enterocyte, di- and tripeptides are almost immediately hydrolyzed into free amino acids by intracellular peptidases before being transported out of the cell and into the bloodstream.

Yes, there are different transporter systems with varying substrate specificities. For instance, System B$^0$ handles neutral amino acids, while the EAAT family transports acidic ones, and the b$^0$,+ exchanger handles cationic amino acids.

After exiting the basolateral membrane of the enterocyte, the absorbed amino acids enter the interstitial fluid and are then collected by the capillaries that form the portal vein, which transports them directly to the liver.

No, while absorption is a major function of the small intestine, most amino acid absorption occurs primarily in the jejunum. The ileum serves to absorb any remaining nutrients not fully processed earlier in the small intestine.