Gastrointestinal Lecture 4 Part 2 Digestion and Absorption of Dietary Proteins

Question 1

dietary protein in diet

Answer 1

A healthy adult requires 40 to 50 g of protein to supply essential amino acids
The average diet contains 60 to 90 g of protein, providing ~1/6 of total caloric intake

In addition to dietary intake, the intestine also receives large amount of protein that is secreted into it in the form of mucus, enzymes and degraded epithelial cells

Regardless of the source, the majority of protein (>95%) entering the intestine is broken down into amino acids and absorbed.

Question 2

How are polypeptides broken down?

Answer 2

• protein digestion requires the breakdown of large complex molecules into their respective building blocks
• Protein digestion primarily mediated by proteolytic enzymes (proteases)
• Because of their powerful activity, many of these enzymes are secreted as inactive precursors, thereby protecting the cells where they are manufactured
• Secreted precursor proteins are activated in the lumen by specific proteins

Question 3

How are polypeptides broken down?

Answer 3

• protein digestion requires the breakdown of large complex molecules into their respective building blocks
• Protein digestion primarily mediated by proteolytic enzymes (proteases)
• Because of their powerful activity, many of these enzymes are secreted as inactive precursors, thereby protecting the cells where they are manufactured
• Secreted precursor proteins are activated in the lumen by specific proteins

Question 4

Protease enzymes can be classified into two major categories:

Answer 4

1) Endopeptidases → Endopeptidases cleave proteins at interior peptide bonds (trypsin, chymotrypsin, elastase)
2) Exopeptidases → Exopeptidases cleave proteins at their n- and c-termini, and are called aminopeptidases and carboxypeptidases, respectively

Question 5

Where does protein digestion begin?

Answer 5

• Highly acidic environment (contains HCl, ~pH 2) → denatures proteins
• Secretes pepsin → proteolytic enzyme cleaves large polypeptides
• The activity of pepsin requires an acidic pH, and will stop working in the more alkaline duodenum

Question 6

protein digestion after the stomach

Answer 6

Protein digestion continues in the small intestine
There are two major sources of proteases that contribute to intestinal protein digestion:

> Pancreatic enzymes
> Intestinal brush border enzymes

Question 7

pancreatic enzymes

Answer 7

• Pancreatic enzymes are activated through the activity of enterokinase and trypsin
• Enterokinase is tethered to the intestinal epithelium. It cleaves trypsinogen to yield trypsin
• Trypsin can activate more trypsinogen, in a feed-forward loop
• Trypsin also cleaves other pancreatic proenzymes into their active forms

Question 8

Intestinal brush border enzymes

Answer 8

Intestinal brush border enzymes include aminopeptidases, carboxypeptidases and endopeptidases (numerous types specific to different peptide bonds)

The activity of these enzymes generate individual amino acids, dipeptides and tripeptides, which can be absorbed by the intestinal epithelium

Dipeptides and tripeptides taken up into intestinal epithelial cells are further broken down in the cytosol to yield individual amino acids by intracellular peptidases

Question 9

Thus, protein digestion can occur in three locations:

Answer 9

1) Intestinal lumen
2) Intestinal brush border
3) Inside intestinal epithelial cells

Question 10

The products of intestinal protein digestion are

Answer 10

amino acids, dipeptides and tripeptides

Question 11

Absorption of proteins requires

Answer 11

uptake and transit through the intestinal epithelium

Question 12

Absorption of dietary protein – dipeptides and tripeptides

Answer 12

• Small peptides (di- and tripeptides) are taken up into epithelial cells by a transport protein called PepT1 (peptide transporter 1)
  
  • This occurs by secondary active transport
• Once inside the cell, these peptides are cleaved by intracellular peptidases into amino acids Amino acids exit the cell by facilitated diffusion through amino acid transporters
• Secondary active transport of small peptides is coupled to the uptake of protons
  
  • The proton gradient is maintained by an apical sodium/hydrogen exchanger (NHE)
  • The sodium gradient is maintained by a basolateral Na/K ATPase

Question 13

Absorption of dietary protein – amino acids

Answer 13

• There are at least seven transport systems that facilitate amino acid uptake into intestinal epithelial cells, the majority of which rely on a gradient of sodium ions.
• Amino acids enter the cell by secondary active transport (coupled to a gradient of sodium ions), and leave the cell via facilitated diffusion
• Similar to small peptides, the sodium gradient driving amino acid uptake is maintained by a Na/K ATPase pump in the basolateral membrane of the enterocyte

Question 14

Protein digestion and absorption summary

Answer 14