Digestion as Chemistry: Enzymes from Mouth to Gut

A sandwich contains starch, protein, fat and a little sugar, mostly as molecules far too large to pass into your blood. Digestion’s job is to break them down into small, absorbable pieces: glucose, amino acids, fatty acids and glycerol. It does this with a single type of chemical reaction, hydrolysis, carried out by a relay of enzymes, each working in its own chemical environment along a nine-metre tube. Here’s the journey from a chemist’s point of view.

The key reaction: hydrolysis

Carbohydrates, proteins and fats are built from smaller units joined by condensation reactions, which release water (see the four major biomolecules). Digestion does the reverse: hydrolysis adds water across each bond, splitting it.

Food molecule	Bond broken	Products absorbed
Starch, disaccharides	Glycosidic bonds	Monosaccharides (glucose, fructose, galactose)
Proteins	Peptide bonds	Amino acids (and some di- and tripeptides)
Fats (triglycerides)	Ester bonds	Fatty acids and monoglycerides (and some glycerol)

These reactions are thermodynamically favourable but extremely slow on their own. Enzymes speed them up enormously (see enzymes: how they work).

Stage 1: the mouth

• Mechanical digestion: teeth break food into small pieces, greatly increasing the surface area for enzymes to act on.
• Saliva: about 1 to 1.5 litres a day, slightly alkaline to neutral (pH about 6.5–7.5), containing:
  • salivary amylase, which begins hydrolysing starch into maltose and shorter chains;
  • a little lingual lipase, which starts on fats;
  • mucus, which lubricates food for swallowing.

Chew a piece of plain bread for a minute or two and it begins to taste sweeter, as amylase releases maltose. Food spends only seconds to a minute in the mouth, so little is digested there.

Stage 2: the stomach

The stomach is a strongly acidic environment. Its lining secretes hydrochloric acid, giving stomach contents a pH of about 1.5 to 3.5 (see stomach acid chemistry).

The acid:

• kills most bacteria in food;
• denatures proteins, unfolding them so that enzymes can reach their peptide bonds (see protein denaturation);
• activates pepsin.

Pepsin is a protease that begins breaking proteins into shorter polypeptides. It’s secreted as an inactive precursor, pepsinogen, which is converted into active pepsin by acid. Secreting it inactive protects the stomach cells that make it from digesting themselves. Pepsin works best at around pH 2, a good example of an enzyme’s optimum pH (see how temperature and pH affect enzymes).

Salivary amylase is inactivated by the stomach acid, so starch digestion pauses here.

The stomach also churns food into a thick liquid called chyme. A layer of mucus and hydrogencarbonate protects the stomach lining from its own acid.

Stage 3: the small intestine (the main event)

Most digestion and almost all absorption happen in the small intestine, which is about 6 metres long.

Neutralising the acid

As chyme enters the first section (the duodenum), the pancreas releases a juice rich in hydrogencarbonate (bicarbonate) ions, which neutralise the stomach acid:

HCO₃⁻ + H⁺ → H₂O + CO₂

The pH rises to about 7 to 8, suiting the pancreatic enzymes. This is essentially an acid–base neutralisation.

Pancreatic enzymes

The pancreatic juice also contains:

• pancreatic amylase, continuing starch digestion into maltose;
• proteases such as trypsin and chymotrypsin, released as inactive precursors and activated in the intestine, which cut proteins into short peptides;
• pancreatic lipase, which hydrolyses fats into fatty acids and monoglycerides.

Bile: emulsifying fat

Fats don’t dissolve in water, so they form large droplets, and lipase can only work at the droplet surface. Bile, made in the liver and stored in the gallbladder, contains bile salts, made from cholesterol (see cholesterol chemistry).

Bile salts are amphipathic: one side of the molecule is non-polar and the other polar. They coat fat droplets and break them into many tiny droplets, an emulsion, just as detergents do. This vastly increases the surface area for lipase. Bile also helps neutralise acid. (See lipids explained.)

Finishing the job: brush-border enzymes

The inner surface of the small intestine is folded and covered in tiny finger-like villi, which are themselves covered in microvilli, forming a “brush border”. Enzymes on these cell surfaces complete digestion:

• maltase, sucrase and lactase split disaccharides into monosaccharides (see disaccharides);
• peptidases split short peptides into amino acids.

Absorption

The folds, villi and microvilli give the small intestine a very large surface area, often quoted as a few hundred square metres, though more careful estimates put it nearer 30 square metres. Either way, it’s enormous for its size.

• Monosaccharides and amino acids are absorbed by transport proteins in the cell membranes, some using energy from ATP, and pass into the blood, which carries them to the liver.
• Fatty acids and monoglycerides diffuse into intestinal cells, where they’re reassembled into triglycerides, packed into lipoprotein particles and released into the lymph.
• Water, vitamins and minerals are also absorbed here.

Stage 4: the large intestine

The large intestine absorbs most of the remaining water and some minerals, turning liquid waste into faeces.

It’s also home to trillions of bacteria, the gut microbiota. They ferment dietary fibre that our own enzymes can’t digest, such as cellulose and other plant polysaccharides (see starch vs glycogen vs cellulose). Fermentation produces:

• short-chain fatty acids (acetate, propionate and butyrate), which feed the cells of the colon and have wider health benefits;
• gases (hydrogen, carbon dioxide and, in some people, methane);
• some vitamins, such as vitamin K and some B vitamins.

Summary: enzymes along the gut

Location	pH	Carbohydrates	Proteins	Fats
Mouth	~7	Salivary amylase	—	Lingual lipase (minor)
Stomach	~1.5–3.5	(Amylase inactivated)	Pepsin	Gastric lipase (minor)
Small intestine	~7–8	Pancreatic amylase; maltase, sucrase, lactase	Trypsin, chymotrypsin; peptidases	Pancreatic lipase (+ bile)
Large intestine	~5.5–7	Bacterial fermentation of fibre	—	—

How long it all takes

Digestion is not quick. Food typically leaves the stomach within about two to four hours, faster for carbohydrate-rich meals and slower for fatty ones, because fat in the small intestine triggers hormones that slow stomach emptying. It then spends several hours in the small intestine, where most absorption happens, and anywhere from about a day to a few days passing through the large intestine. The whole journey commonly takes one to three days. Fibre speeds things up by adding bulk and holding water.

When digestion goes wrong

• Lactose intolerance: too little lactase; undigested lactose is fermented by bacteria, causing gas and discomfort.
• Coeliac disease: an immune reaction to gluten proteins damages the villi, reducing absorption.
• Gallstones: crystals, often of cholesterol, block bile flow, impairing fat digestion.
• Pancreatic insufficiency: too few pancreatic enzymes, leading to poor digestion of fats and proteins.

Key takeaways

• Digestion breaks large food molecules into small ones by hydrolysis, catalysed by enzymes.
• Amylases break down starch, proteases proteins and lipases fats; brush-border enzymes finish the job.
• The stomach (pH ~2) denatures proteins and activates pepsin; hydrogencarbonate from the pancreas neutralises acid in the small intestine.
• Bile salts emulsify fats so lipase can work.
• Absorption happens mainly in the small intestine; gut bacteria ferment fibre in the large intestine. For the first step, the sense of taste, see the chemistry of taste.