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Protein Digestion & Absorption

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Protein Digestion & Absorption

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  • Here, we will learn about protein digestion.
  • Start a table.
  • Denote that protein digestion generally refers to protein breakdown and absorption.
  • Denote that this occurs through:
    • Denaturation
    • Peptide bond cleavage (which, itself, is commonly referred to as digestion)
    • Peptide Uptake
    • Amino Acid Absorption
  • Denote that denaturation refers to protein unfolding (uncoiling), which occurs in the highly acidic gastric milieu, where the pH is ~ 2.
  • Peptide bond cleavage refers to the enzymatic activity of proteases (peptidases), which catalyze hydrolytic peptide bond cleavage, most prominently by pancreatic enzymes within the proximal small intestine, where the pH is ~ 6.
  • Peptide uptake refers to the uptake of short peptides into enterocytes (brush border cells along the small intestine), where they are further cleaved into individual amino acids.
  • Amino acid absorption refers to the diffusion and transport of amino acids out of enterocytes and into the surrounding capillaries for systemic dispersion.
  • To begin, draw a head and esophagus.
  • Next, draw the stomach, then the small intestine, and the pancreas.
  • Indicate that in Western nations, we consume ~ 100 grams/day of dietary protein (70 to 100 grams/day); we see that protein is in its coiled (folded) state.
  • Indicate that another ~ 100 grams/day of protein (35 to 200 grams/day) enters the gut endogenously these are the nitrogen-containing materials that pass into the gut: the digestive enzymes, desquamated cells, bile salts, phospholipids, lysed cells, plasma proteins, etc…).
  • Now, indicate that we use the laboratory value of fecal nitrogen excretion to measure protein absorption efficiency.
    • Poor protein digestion and absorption means that proteins pass through our GI system and into our fecal waste, unabsorbed.

To fully understand protein digestion, let's build a protein, starting from the chemical makeup of an amino acid.

  • Draw an amino acid as follows:
  • Draw a central carbon (the alpha carbon) atom with the following bound to it:
    • Hydrogen atom
    • Carboxylic acid (COOH) group
    • Amino (NH2) group
    • Variable, R, group.
  • Indicate that we've completed one amino acid, which we represent as a single oval.
  • Now, indicate that dipeptides comprise 2 amino acids joined to it via a peptide bond (aka amide bond).
  • Next, show that oligopeptides have 2 – 10 amino acids (note some authors define oligopeptides as having up to 20 amino acids).
  • Polypeptides comprise 10 – 50 amino acids.
  • Proteins comprise > 50 amino acids.

Next, consider which of the amino acids are absorbed from the diet and which are biosynthesized?

  • Indicate that it's the 9 essential amino acids (of the 20 total amino acids).
    • Thus, the environment provides ~ half of the amino acids we require to live (the other half we build endogenously).

Let's review the essential amino acids, now, with the simple (cheeky) acronym:

  • My Tall (Handsome) Vegan Friend Is Watering Kale Leaves.
    • M for Methionine, T for threonine, H for histidine, V for valine, F for phenylalanine, I for isoleucine, W for tryptophan, K for lysine, L for leucine.

Let's indicate highlights of these amino acids.

  • Use a prototypical branched chain to indicate the clinically-important branched chain amino acids: valine, isoleucine, and leucine.
  • And place an asterix on histidine because it is only fully essential in diets in childhood.
  • Indicate that the two L's (Lysine and Leucine) are ketogenic.
  • The mnemonic "These amino acids don't FITTT" helps us remember that Phenylalanine, Isoleucine, Tryptophan, Threonine, and Tyrosine are neither glucogenic or ketogenic alone – they are both glucogenic and ketogenic.
  • And the rest are glucogenic: methionine, histidine, and valine.

Let's begin our understanding of protein break-down with denaturation.

  • Show that the stomach has a highly acidic pH of ~2 (range of 1.5 – 4.5) because of its HCl secretion.
    • Indicate that rather than this acidity being integral for protein digestion, it is key to protein denaturation (uncoiling, unfolding), which helps prepare proteins for peptide bond breakage (digestion) via protease (peptidase) catalyzed hydrolysis.
  • So, next indicate the various proteases that perform GI peptide bond cleavage.
    • The stomach secretes pepsin (as pepsinogen).
    • The pancreas secretes trypsin, chymotrypsin, elastase, and carboxypeptidase (all in their zymogenic form).
    • Aminopeptidases are found in the enterocytes of the small intestine.
    • Without proteolytic enzymes (proteases, peptidases), it would take years for proteins to be broken-down (at neutral pH).
    • With proteases, protein degradation occurs within milliseconds!
  • Show that the proximal small intestine has a borderline acidic pH of ~6 because of pancreatic bicarbonate secretions – this is where that most protein digestion and amino acid absorption occurs.
    • [For reference, the distal small intestine has a slightly alkalotic pH of ~7.5 and the colonic pH fluctuates widely from 5 – 8].

Now, let's draw out the pathways of protein digestion and absorption.

  • Draw a section of small intestine.
  • From inside to out, specify the intestinal lumen and the intestinal villus.
  • Within the villus, draw an enterocyte with its characteristic brush border (the absorptive microvilli) on the apical surface and then adjacent to the basolateral surface of the enterocyte, indicate interstitial fluid and draw a blood vessel.
  • Within the intestinal lumen, draw a protein – a polypeptide chain of > 50 amino acids.
  • Then, show a prototypical pancreatic peptidase, which cleaves (digests the protein) into oligopeptides (chains of several amino acids) and tri- and dipeptides or single amino acids.
  • Next, show that brush border peptidases line the apical surface.
  • Indicate that oligopeptides are cleaved into smaller oligopeptides, which can:
    • Enter the enterocyte via oligopeptide transporters OR
    • Be further cleaved into tri- or dipeptides or amino acids, which enter via specific transporters.
  • Next, show that cytosolic peptidases (proteases inside the enterocytes) further digest the peptides into amino acids.
  • Finally show that all the aforementioned products pass through transporters on the basolateral aspect of the enterocyte, through the interstitial fluid, and into blood vessels for systemic distribution.
    • Again, mostly it's amino acids (rather than peptide chains) that enter the blood stream.

Finally, let's create some general rules to consolidate the numerous peptide and amino acid transporters.

  • Indicate that, generally, oligopeptides enter the apical aspect of enterocytes via proton-dependent transporters (referred to as PepT1), whereas, amino acids enter via sodium-dependent transporters (eg, SLCA19).
  • Then, indicate that amino acids exit the basolateral surface of enterocytes in a wide-range of mechanisms: simple and facilitated diffusion or active transport whereas, generally, amino acids enter enterocytes via sodium-dependent transporters (just like on the apical side).
  • Finally, consider the purpose of the basolateral uptake of amino acids – it's important for intracellular protein synthesis; the synthesis of the protein machinery that runs the cell.

Key References

  • Koziolek, M., Grimm, M., Becker, D., Iordanov, V., Zou, H., Shimizu, J., Wanke, C., Garbacz, G. and Weitschies, W. (2015), Investigation of pH and Temperature Profiles in the GI Tract of Fasted Human Subjects Using the Intellicap® System. J. Pharm. Sci., 104: 2855–2863. doi:10.1002/jps.24274
  • Shils, Maurice and Shike, Moshe. Modern Nutrition in Health and Disease, 10th edition. Lippincott, Williams, & Wilkens. New York.