IV.  Nutrient Digestion and Absorption
      
       The majority of absorption occurs in the small intestine where the final site of hydrolysis takes place.  In fact, many authors will separate intestinal digestion into two phases; luminal and membranous.  Luminal representing that which occurs in the intestinal lumen and is primarily driven by pancreatic enzymes, and membranous digestion representing the final hydrolysis driven by enzymes from the intestinal mucosa (enterocytes). 

       Enterocyte enzymes tend to stay embedded in the microvilli and mucus layer.   This is a logical way to distinguish the role of the intestinal enzymes from the pancreatic enzymes.  Pancreatic enzymes will accomplish the crude hydrolysis, chopping proteins and starch into smaller and smaller fragments, while the enterocyte enzymes will complete the hydrolysis into absorbable monomers.  Final hydrolysis occurs at the site of absorption.

       Absorption of nutrients is the ultimate objective of digestion but is not a casual extension of the processes discussed so far.  The cell membrane of the mucosal epithelium presents a barrier to movement of molecules and the mechanisms that have evolved to get molecules from the lumen into the enterocyte, and from the enterocyte into the blood are, in most instances, specific for each nutrient (transporting epithelia).  For this reason, mechanisms of absorption are important to understanding the complexity of the digestive process.  In addition, digestive disturbances are common in animals and can result from problems in either preparing nutrients for absorption or absorbing nutrients from the GIT into the blood.  Understanding the cause of the problem helps to understand the therapy.

    The submucosa of each villus contains blood and lymph vessels as well as nerves.  This makes sense because cells need nutrients but these vessels will also carry away the nutrients that are absorbed through the enterocyte.


The submucosa of each villus contains blood and lymph vessels as well as nerves.




  As illustrated and discussed at the CO site, some nutrients are small enough to get through the 'tight junctions' that tend to restrict most nutrients (paracellular), while most require transport across the membrane (transcellular). 

                                   


    Getting nutrients into the enterocyte is half the story because it is also necessary to get the nutrient back out of the cell and into the blood stream.  This diagram illustrates the process of glucose absorption, but for now simply recognize that mechanisms must exist for both entry and exit as illustrated.  Another point to keep in mind is that once nutrients are in the blood stream they will be carried to every cell of the body, but once delivered, each cell must have mechanisms to absorb the nutrients from the blood or interstitial fluid.  The membrane barrier that exists in the intestine, exists in every cell.

   


     Looking at this transport model for glucose you will note that a glucose transport protein is present on the luminal side (Na glucose symporter) and on the basement membrane or blood side (Glut2).  All cells will have glucose transport proteins on the basal surface that provide the mechanism for the cell to extract glucose from the blood.  The same is true for other nutrients.  A primary point of this is to realize that understanding the mechanisms for transporting nutrients from the GIT provides insight into how all cells of the body absorb nutrients from the blood.


       A.  Mechanisms of Transport
          The mechanisms for transport across membranes is illustrated in following  two diagrams.


         
1.  Passive Transport.  The driving force is the concentration gradient for the nutrient across the membrane.  Passive transport can be further divided into:
                   a.  Diffusion.  In order for molecules to simply diffuse across a membrane, they must either be quite small so as to enter membrane pores, go via the paracellular route, or be soluble in the lipid membrane.  Water is a good example of a small molecule as are the gases and ethanol.  Many lipids  are soluble in the lipid bilayer and are transported by simple diffusion.

                   b.   Facilitated diffusion.  As the diagram illustrates, transport is facilitated by a transport protein but the driving force is still the concentration gradient.  Glucose and amino acids use this mechanism.

          2.  Active Transport.  Active transport also uses a transport protein, but energy is required in the form of ATP to move nutrients against a concentration gradient.  The best example of this mechanism is the Na+/K+ pump that is present in every cell.  Transport of glucose and amino acids is also active in the GIT.

         3.  Endocytosis and Exocytosis.   Some molecules are simply to big to get across the membrane by the mechanisms outlined above.  As illustrated in the diagram, in response to the presence of the molecules, the cell membrane invaginates, surrounds and engulfs the molecules.  Once inside, the membrane is disassembled and the contents are released.  Conversely, molecules can exit a cell by exocytosis.  Again, molecules are packaged into a membrane compartment that fuses with the cell membrane, releasing the contents to the opposite side.  We will see that absorption of intact proteins such as antibodies occur in the manner. 
      

       Supplemental reading.


       B.  Absorption of key nutrients

          1.  Glucose.  Glucose is the final end product from the hydrolysis of the majority of carbohydrates in an animals diet (starch).  Other monosaccharides are also generated in smaller quantities from ingesting carbohydrates such as lactose or sucrose.  We will only consider glucose.  Referring to the diagram above illustrating glucose transport, you will note that the transport protein is called a Na-glucose symporter.  That means that the protein binds both glucose and Na+.  This mechanism is unique to the intestine and the kidney, and is designed to optimize glucose absorption.  Instead of simply relying on the glucose gradient, coupling to Na+ permits a very efficient means to get glucose out of the lumen even at low concentrations.  This is because the Na+ gradient is maintained by the Na+/K+ pump so that there is always a Na+ gradient into the cell.  Because the Na+/K+ pump is 'active transport", glucose transport from the GIT into the cell is also considered 'active transport'.  The transport protein that gets glucose out of the cell to the blood relies only on the concentration gradient created by glucose uptake into the cell.  This mechanism is therefore passive using facilitated diffusion.   This protein can transport into or out of the cell depending on the glucose concentration.  Once glucose is in the blood, glucose concentration is typically higher than in most cells, so delivery of glucose to cells relies on the glucose gradient from blood into the cell. 

          2.  Amino Acids.  Singular amino acids (and some di- or tripeptides) are the end products of protein hydrolysis.   Amino acid absorption uses a mechanism similar to glucose.  A Na+ dependent co-transporter assures efficient absorption and is considered active transport like that of glucose.  Several different transport proteins are needed to accommodate the wide array of amino acids that must be absorbed.

          3.  Fat (triglyceride).  Fat digestion and absorption is more complex than for other nutrients, so we will develop this story in greater detail than for other nutrients.  Triglyceride (TG) is the major component of the lipids ingested by animals, but other components such as cholesterol have a different chemistry and subtly different requirements for digestion/absorption.  Our primary focus will be on TG. 

            Because fats are not water soluble and the media in which enzymes are dissolved is aqueous, several features of fat hydrolysis and absorption are unique.

                   a.  Bile acids are used to 'emulsify' fats to make them water miscible in order for digestive enzymes such as lipase to act.

                   b.  Bile acids also function to transport hydrolyzed lipids to the enterocyte membrane for absorption.

                   c.  Because fats are soluble in the lipid bilayer of the enterocyte membrane, absorption is by simple diffusion.

                   d.  Once in the enterocyte, lipids must be made water miscible for transport in blood.  This is accomplished in a series of steps that includes; 1) remaking TG by re-esterifying the fatty acids to the monoglyceride, 2) packaging the TG along with cholesterol and other lipids and protein into a water miscible complex called a lipoprotein.  Lipoproteins come in different flavors (classes).  The one that is formed in the enterocyte is called a chylomicron. 

                    e.  Chylomicrons are quite large particles.  This presents new problems for the cell.  First, to get it out of the cell, exocytosis is used.  Second, the chylomicron is too large to enter the blood capillaries of the villus.  Instead, chylomicrons enter the lymph vessels (lacteal) to be transported along with other cell fluids to the blood stream as we have seen previously.

          This figure outlines the events that take place within the enterocyte.  After hydrolysis,  monoglyceride (acylglycerols) and fatty acids (free fatty acids) are absorbed along with other lipids such as cholesterol.  Once in the cell, TG are reformed and packaged into the chylomicron complex, which are carried by the lymph vessels to the blood stream.  Short chain fatty acids and glycerol can escape this complexity and be absorbed directly into the bloodstream.  Short chain fatty acids such as the VFA's in ruminants would follow this route.
        

 

       Here is an artists depiction of a chylomicron.  This class of lipoproteins is particular rich in TG.


    
         


        Bile acids are secreted from the gallbladder in response to CCK.  Imagine a chunk of TG such as a pat of butter floating along in the GIT.  The action in the stomach helps break the chuck into smaller bits, but it is still not in form that an enzyme can attach to.  Once the TG enters the duodenum and stimulates CCK secretion, bile acids act as detergents to emulsify the TG.

             What does this mean?  Detergents are polar molecules that when placed in an aqueous media naturally form 'micelles'.  A micelle is an aggregate that has the polar groups oriented to the outer aqueous media with the non polar groups in the core.  The lipid bilayer of a cell membrane is an example (left), as is the micelle formed when detergent is placed in water (right)




Micelles.
   The red dot is the polar head (P) and the blue tails are non-polar fatty acids extending into the core (U).


 






            Bile acids are able to physically disrupt the hydrophobic interactions that hold the butter together resulting in very small particles composed of bile acids and lipids in a micelle structure.  Now lipase can get to the TG to complete the hydrolysis.  The end product of lipase hydrolysis are monoglycerides and fatty acids.  These end products are not very soluble either and are also mixed with bile acids to form additional micelles.  This process is illustrated in the inset below

  

        This diagram also illustrates how monoglycerides and fatty acids are absorbed, re-esterified to TG, packaged into chylomicrons and secreted into the lymph. 

























            4.  Water.  Water is absorbed passively all along the GIT.  Being a small molecule, water can pass through pores within the membrane or between the cells.  The driving force is always osmosis, so water can can be drawn from the blood or taken into the blood depending on osmotic pressure.  Both occur, and disturbances in GIT function often lead to water losses that can be life threatening.  The process of osmosis is illustrated below.

                          

          As food is digested and hydrolyzed considerable quantities of water are drawn into the GIT to generate an isotonic environment.  As nutrients are absorbed gut contents become hypotonic and water is absorbed.  As more and more nutrients are absorbed so is water.  So water absorption is highly dependent upon nutrient absorption.