Absorption of water, minerals and vitamins

More absorption stuff! Once again, this lecture was largely a recap of PHYL2001, but there's some new stuff too!

Describe the mechanisms used for water absorption by the GIT.

The gastro-intestinal tract cannot actively transport water, so water is mainly transported by following an osmotic gradient. Usually this osmotic gradient is formed when some other solute (such as sodium) is absorbed or secreted.

Describe transcellular and paracellular absorption.

Transcellular: through cells. Paracellular: next to cells. Transcellular absorption often requires that channels, pumps, etc. be present on the apical and basolateral cell membranes, as many solutes (particularly charged ions, like sodium and potassium) cannot readily pass through a cell membrane. Paracellular absorption occurs through the tight junctions, and is dependent on how "tight" the tight junctions are. The "tightest" tight junctions are in the colon, whereas the "leakiest" tight junctions are in the small intestines.

Outline the roles of tight junctions and aquaporins in regulating water absorption.

Aquaporins are basically channels that allow water (and sometimes also hydrogen peroxide) to pass through. Both tight junctions and aquaporins allow water to flow down its osmotic gradient, allowing for the absorption and secretion of water.

Outline the importance of electrolytes in water absorption.

As I mentioned earlier, water travels down its osmotic gradient. The osmotic gradient, in turn, is set up by concentrations of electrolytes. Therefore, transport of electrolytes also affects the transport of water.

Name the transporters involved in absorption of major electrolytes/minerals.

Sodium

Sodium transport mechanisms are slightly different in different areas of the GI tract. Pretty much all of these mechanisms rely on the action of the Na⁺/K⁺ ATPase to keep the Na⁺ concentration within the cell low, creating a nice concentration gradient.

• Duodenum and jejunum: Na+ is taken up by an Na+/H+ antiport. This antiport also stops the inside of the cells from getting too acidic.
• Jejunum and ileum: Na+ is taken up by secondary active transport with glucose or amino acids.
• Ileum and proximal colon: These areas have both Na+/H+ antiports and Cl-/HCO3- antiports.
• Distal colon: Passive Na+ channels.

Chloride

Eh, I think I'll split this one up in terms of mechanism, rather than location (as the areas in which these transport processes occur overlap a lot more for chloride than they do for sodium).

• Passive absorption: Occurs via paracellular and transcellular routes. Cl- often follows Na+. Occurs in the jejunum, ileum and distal colon.
• Cl-/HCO3- antiports: Ileum, proximal colon and distal colon.
• Parallel Na+/H+ and Cl-/HCO3- antiports: Ileum and proximal colon (same as for sodium, which makes sense because it's essentially the same mechanism).

There are four main types of chloride channels. These include calcium-activated chloride channels (CaCC), volume regulated anion channels (VRAC), ligand-gated anion channels (LGAC) and the CFTR channel. The CFTR channel, which is regulated by cAMP, is of particular interest as it is this channel that is non-functional in cystic fibrosis patients. cAMP activates protein kinase A, allowing it to phosphorylate the R-domain of the channel, causing it to open. As such, when cAMP levels increase, chloride secretion increases, causing water secretion to increase, and a shit-ton of diarrhoea (pun intended) results.

Potassium

• "Solvent drag": When water moves down an osmotic gradient, some potassium can be dragged along with it. This phenomenon is found in the jejunum and ileum.
• Active absorption: H+/K+ pumps in the distal colon. This is quite energy-expensive.

Calcium

Some calcium can be absorbed via the paracellular route throughout the small intestine. Calcium can also be absorbed via the transcellular route in the duodenum. Absorption happens through the CAT1 calcium channel on the apical surface. Once in the cell, calcium binds to calbindin (to stop free calcium from setting off a whole bunch of other reactions). It can then be pumped out through pumps on the basal side. Transcription of the CAT1 gene relies on vitamin D, which is why vitamin D is important for calcium absorption.

Magnesium

Magnesium is absorbed in a similar way to calcium, except that the channel on the apical surface is called TRPM6, and no binding proteins are required.

Other random notes on mineral absorption

There are several different factors that can affect how much of a given mineral is absorbed. These include pH, the oxidation state of the metal (as mentioned here, Fe³⁺ is much less soluble than Fe²⁺), and the presence of certain dietary complexes (e.g. ascorbate can increase absorption, whereas phytates can reduce absorption). Fun fact: calcium blocks lead absorption, which is useful for treating lead poisoning.

Describe the different mechanisms used for absorption of water-soluble and lipid-soluble vitamins.

Water-soluble vitamins are mostly absorbed by specific transporters (with the notable exceptions of B9 and B12, which I'll discuss in a bit). Fat-soluble vitamins (A, D, E and K) are even simpler: they're absorbed along with fats (see here for information on how fats are absorbed). The flipside of this is that when fat absorption is inhibited (by a bile duct blockage etc.), fat-soluble vitamin absorption is also inhibited.

Now back to B9 and B12! B9 absorption isn't too complicated. As I mentioned here, B9 is often joined to a bunch of glutamate residues, so those residues need to be "chopped off" first before B9 can be absorbed. Not to worry: we have enzymes on the brush border that do just that! Once folate is inside the enterocytes, it is methylated and reduced before being released into the blood.

B12 absorption is pretty complicated. In the stomach, B12 binds to haptocorrin, which is secreted by gastric glands. Intrinsic factor, as mentioned here, is also released from the stomach, but it cannot bind to B12 at such a low pH. Once the B12-haptocorrin complex enters the duodenum, proteases degrade haptocorrin, allowing B12 to bind to intrinsic factor. The B12-intrinsic factor complex can be taken up in the ileum via clathrin-coated vesicles. The vesicles then acidify, allowing B12 to be released from intrinsic factor. B12 is then packaged with trans-cobalamin II for transport around the body.