Questions on digestion and absorption in the human gut

Question 1

Explain why a mixture containing only exopeptidases would digest a protein far more slowly than one that contains endopeptidases as well.

Accepted Answer

B1 an exopeptidase hydrolyses the peptide bond at an end of a chain, removing one amino acid at a time, so it can only work where there is a free end B1 a chain of three hundred amino acids has only two ends, so the number of places an exopeptidase can start is very small however much enzyme is present B1 an endopeptidase hydrolyses peptide bonds in the interior of the chain, and each internal cut produces two more ends B1 far more ends means far more sites at which the exopeptidases can act at the same time, so the overall rate of hydrolysis rises

Question 2

Explain how bile salts increase the rate at which lipid is digested, and explain how micelles help the products of that digestion to be absorbed.

Accepted Answer

B1 bile salts are amphipathic, coating a lipid surface with the hydrophobic face inwards, so the droplets repel one another instead of merging and the churning of the gut can break them into much smaller ones that stay broken B1 that emulsification greatly increases the total surface area of lipid, so more ester bonds are accessible to water-soluble pancreatic lipase and the rate of hydrolysis rises, although bile itself breaks no bond B1 monoglycerides and fatty acids, with bile salts and any fat-soluble vitamins, assemble into micelles that carry them through the watery layer next to the epithelium and release them at the membrane, keeping the concentration of free products high there B1 the micelle itself is not absorbed: monoglycerides and fatty acids are small and non-polar, so they diffuse straight through the phospholipid bilayer by simple diffusion

Question 3

Describe how glucose is absorbed from the lumen of the ileum into the blood, making clear where in the cell ATP is used.

Accepted Answer

B1 a sodium-potassium pump in the basal membrane hydrolyses ATP and moves three sodium ions out of the epithelial cell for every two potassium ions in, so the sodium concentration inside the cell falls below the concentration in the lumen B1 a co-transporter protein in the apical membrane binds one glucose molecule together with two sodium ions B1 sodium moves into the cell down the electrochemical gradient the pump created and glucose is carried in with it, against its own concentration gradient, with no ATP hydrolysed at this membrane B1 glucose then leaves the far side of the cell into the blood by facilitated diffusion through a different carrier protein, down the gradient its accumulation has created

Question 4

Compare pancreatic amylase with maltase, referring to where each enzyme is found, the bond each hydrolyses, the product of each, and one advantage of the difference in position.

Accepted Answer

B1 both are carbohydrases and both catalyse a hydrolysis, adding a water molecule across a glycosidic bond, and neither is absorbed itself B1 pancreatic amylase is secreted into the lumen of the duodenum and works free in solution, whereas maltase is built into the cell-surface membrane of the ileum epithelium with its active site facing the gut contents and is never released into the lumen at all B1 amylase hydrolyses the 1,4 bonds of starch and cannot touch the 1,6 bonds at a branch point, so it yields maltose and short branched fragments, whereas maltase hydrolyses the single bond of maltose and yields two glucose molecules B1 amylase therefore leaves a disaccharide that still cannot be absorbed, whereas maltase releases glucose a few nanometres from the co-transporter that takes it in, so it is absorbed before it can diffuse away or be taken by gut bacteria

Question 5

The table gives idealised dimensions for the folding of the ileum, constructed for this question rather than measured. Treating a villus and a microvillus each as a cylinder, ignoring its tip and the flat wall between neighbouring projections, calculate the factor by which the villi multiply the surface area of a flat gut wall, and calculate the factor by which the microvilli then multiply it again.

Accepted Answer

M1 curved surface area of a cylinder = π × diameter × length, so one villus offers π × 100 × 800 = 2.5 × 10⁵ µm² A1 25 villi stand on each square millimetre, which is 1 × 10⁶ µm² of flat wall, so 25 × 2.5 × 10⁵ = 6.3 × 10⁶ µm² and the villi multiply the area by about 6.3 M1 one microvillus offers π × 0.10 × 1.0 = 0.314 µm², so 3000 of them offer 3000 × 0.314 = 940 µm² on a cell whose unfolded surface is 100 µm² A1 the microvilli multiply the area by about 9.4, and the two factors multiply together, giving 6.3 × 9.4 = about 59 times the area of the same length of unfolded tube

Question 6

An adult who has always drunk milk without difficulty has an infection that destroys much of the epithelium lining her ileum. For several weeks afterwards, milk gives her bloating and watery faeces. Suggest why the infection has this effect, and suggest why the symptoms then disappear.

Accepted Answer

B1 lactase, like the other disaccharidases, is built into the cell-surface membrane of the ileum epithelium rather than secreted into the lumen, so destroying that epithelium destroys the enzyme even though the pancreas is undamaged B1 lactose is therefore not hydrolysed to glucose and galactose, and a disaccharide is too large to be absorbed, so it stays in the lumen B1 the solute left in the lumen lowers the water potential of the gut contents, so water moves out of the epithelium into the lumen down the water potential gradient by osmosis, and the faeces are watery B1 bacteria in the large intestine ferment the lactose and release gas, which distends the gut and causes the bloating; the epithelium is replaced from dividing cells within a few weeks, restoring the membrane-bound enzyme, so the intolerance is temporary rather than the permanent kind set by which alleles a person carries

Question 7

Explain why pepsin is secreted by the stomach as inactive pepsinogen rather than as active pepsin, and explain how it is activated once it is safely in the stomach lumen.

Accepted Answer

B1 pepsin is an endopeptidase, and if it were active while still inside the cells that make it, or in the gastric glands that release it, it would hydrolyse the proteins of those cells and glands themselves B1 secreting it as pepsinogen, an inactive form, avoids this: pepsinogen's active site is not exposed or correctly shaped, so it cannot hydrolyse peptide bonds until it is changed B1 once pepsinogen reaches the acidic stomach lumen, the low pH converts it into active pepsin B1 this activation happening only once the enzyme is outside the cells that made it protects the stomach lining and the secreting cells from being digested by their own product

Question 8

Some people experience bloating after consuming large amounts of fruit juice or foods sweetened with high-fructose syrup, even though they digest lactose and sucrose normally. Suggest why fructose in particular can cause this, given how fructose crosses the ileum epithelium.

Accepted Answer

B1 fructose is absorbed by facilitated diffusion through its own carrier protein in the apical membrane, unlike glucose, which is co-transported with sodium ions B1 because facilitated diffusion depends on a concentration gradient rather than being able to move fructose against one, and the carrier itself can be saturated once the fructose concentration is high enough, a very large intake can arrive faster than the carrier can absorb it B1 fructose that is not absorbed remains in the lumen and passes on into the large intestine B1 there it lowers the water potential of the gut contents, drawing water in by osmosis, and is fermented by gut bacteria, producing gas; both effects together cause the bloating, although here the sugar is failing to be absorbed rather than failing to be digested

Question 9

Describe what happens to monoglycerides and fatty acids once they have diffused into an epithelial cell of the ileum, from arrival at the cell to leaving in the lymph.

Accepted Answer

B1 the smooth endoplasmic reticulum of the epithelial cell re-forms the monoglycerides and fatty acids into triglycerides B1 the Golgi apparatus wraps the triglyceride, together with cholesterol, in a coat of phospholipid and protein, forming a chylomicron B1 the chylomicron leaves the cell by exocytosis into the lacteal, the blind-ended lymph vessel at the centre of the villus, rather than into a blood capillary, because it is far too large to cross into one B1 the lymph eventually rejoins the blood near the left shoulder, so absorbed fat reaches the general circulation without first passing through the liver, unlike glucose and amino acids, which are absorbed straight into the blood capillaries of the villus

Question 10

Compare how glucose is absorbed across the ileum epithelium with how a fatty acid is absorbed, referring to the mechanism used at the apical membrane and the vessel each enters on the other side of the cell.

Accepted Answer

B1 glucose crosses the apical membrane by co-transport with sodium ions, against its own concentration gradient, whereas a fatty acid crosses the same membrane by simple diffusion, needing no carrier and no gradient set up by a pump B1 glucose then leaves the far side of the cell into a blood capillary by facilitated diffusion, whereas a fatty acid is first rebuilt into a triglyceride and packaged into a chylomicron before leaving into the lacteal B1 glucose absorption therefore depends indirectly on ATP, spent by the sodium-potassium pump maintaining the sodium gradient, whereas the absorption of a fatty acid across the apical membrane uses no ATP at all B1 the different vessel each enters follows from size: glucose is small enough to enter a blood capillary directly, while a chylomicron is far too large to do so and must instead enter the wider-gapped lacteal

Question 11

A patient has had a long section of the ileum removed by surgery. Suggest why the patient loses body mass, and suggest why the faeces contain an unusually high proportion of fat.

Accepted Answer

B1 much of the surface area for absorption has gone, with fewer villi and microvilli, so fewer products of digestion are absorbed before the contents pass on to the large intestine B1 less glucose and fewer amino acids are absorbed, so less substrate is available for respiration and stored lipid and body protein are respired instead, and mass falls B1 monoglycerides and fatty acids are also absorbed across the ileum epithelium, so with less epithelium available a greater proportion of the products of lipid digestion is left in the lumen and leaves in the faeces

Question 12

Explain how the acidity of the stomach makes proteins easier for pepsin to hydrolyse, beyond simply activating the enzyme itself.

Accepted Answer

B1 at pH 2 many of the hydrogen bonds and ionic bonds holding a protein's tertiary structure together are disrupted, so the polypeptide chain unfolds B1 peptide bonds that were previously buried inside the folded tertiary structure, and so inaccessible, become exposed on the unfolded chain B1 pepsin can therefore hydrolyse those newly exposed bonds

Question 13

Name the two monosaccharides produced when sucrase hydrolyses sucrose, name the two monosaccharides produced when lactase hydrolyses lactose, and name the structure in the ileum that holds both enzymes.

Accepted Answer

B1 sucrase hydrolyses sucrose to give one molecule of glucose and one of fructose B1 lactase hydrolyses lactose to give one molecule of glucose and one of galactose B1 both enzymes, like maltase, are built into the cell surface membrane of the ileum epithelium rather than released free into the lumen

Question 14

Name the enzyme that hydrolyses maltose, and name the exact place in the ileum at which that enzyme is found.

Accepted Answer

B1 maltase, which hydrolyses maltose to two glucose molecules B1 it is built into the cell-surface membrane of the epithelial cells lining the ileum, with its active site facing the gut contents

Question 15

State the approximate pH of the stomach and the approximate pH of the duodenum, and state what would happen to pancreatic enzymes such as amylase if the acid arriving from the stomach were not neutralised.

Accepted Answer

B1 the stomach is at about pH 1.5 to 2.0, and the duodenum is at about pH 7 to 8 B1 pancreatic enzymes such as amylase, trypsin and lipase have optima between about pH 7 and 8 and would be denatured by the acid arriving from the stomach if it were not neutralised by hydrogencarbonate ions

Quantity	Value
Length of one villus	800 µm
Diameter of one villus	100 µm
Number of villi on each square millimetre of gut wall	25
Length of one microvillus	1.0 µm
Diameter of one microvillus	0.10 µm
Number of microvilli on one epithelial cell	3000
Upper surface of one epithelial cell, unfolded	100 µm²