Chapter 3: Digestion

Digestion

all intermediate processes, including absorption

absorption of food requires

conversion (= hydrolysis) of (non-soluble) polymers in (soluble) monomers

complex digestive tract with 4 zones:

• reception zone (mouth)

• transport zone (oesophagus)

• digestive zone

  • mechanical and enzymatic pre-digestion (stomach)

  • complete digestion and absorption (small intestine)

• absorption of water with formation and excretion of faeces

Reception zone - oral cavity

• reduces particle size of food and stimulates enzymatic digestion by increasing the surface size

• breakdown ~ intensity of chewing + residence time in the mouth

• chewing = age dependent

A slower transformation of food structure induces …

satiation and satiety

summary oral processing

Formation of tooth caries

Tooth enamel

• covered with a biofilm of 

  • enzymes

  • glycoproteins

  • mucins

• Bacteria in the mouth can adhere to the biofilm (e.g. Streptococcus)

Caries formation

• Leuconostoc mesenteroïdes sectretes glucosyl-transferase which produces dextran starting from sucrose → dextran attaches to enamel and will attract acidifying bacteria → tooth caries

Treatment

• oral hygiene

• sugar replacers (e.g. fructose instead of sucrose)

Salivary glands

• stimulated via taste- and smell receptors

• stimulated by conditioned reflex

• secretion is promoted by chewing

components saliva

• ptyalin (alfa-amylase for hydrolysis of endogenous alfa-1,4 bonds in starch)

• HCO3- = creating neutral environment for ptyalin

• Cl- = activation of ptyalin

• mucins = glycoproteins that glue and lubricate the food

• lysozyme

• IgA

papilla

taste buds on tongue that only react to soluble components

Tastes of tongue summary

Tastes of tongue: Umami

Receptor

• T1R1 + T1R3

Recognition

• L-glutamate

• Nucleotide enhancers: IMP (inosin) , GMP (guanosin)

Tastes of tongue: Sweet

Receptor

• T1R2 + T1R3

Recognition

• Sugars (glucose, fructose, sucrose)

• Sugar alcohols (sorbitol)

• D- amino acids

• artificial sweeteners (saccharin and aspartame)

• proteins (monellin, brazzein)

Tastes of tongue: Bitter

Receptor

• T2R receptor (very sensitive, but lack in selectivity

Recognition

• salicin

• phenyltiocarbamide (PTC)

• 6-n-propylthiouracil (PROP)

• saccharin → in high concentrations

• denatonium

Tastes of tongue: Salty

Receptor

• ENaC = epithelial Na channel → not necessary in humans

Recognition

• Na+

• other ions (such as K+)

• dipeptides

!! Narowness of alfa-, beta- or gamma-canals/loops => only sodium can pass through

Tastes of tongue: Acid

Receptor

• PKD2L1

Extra

• CA = carbonic anhydrase: converts CO2 into bicarbonate ions and a proton (e.g. carbonated drinks)

Recognition

• intracellular proton concentrations (pHi)

• Extracellular protons are taken up by taste cells or organic acids = dissociate in cytoplasm

Taste also plays a role in

• Food intake

• Immune function

• Glucose uptake

• Transsit time

• Insulin release

G protein coupled receptors (GPCR)

role in nutrient sensing including

• sweet taste receptors

• amino acid taste receptors

• free fatty acid receptors

Gustary G-protein (gustducin)

linked to GPCR lead to IP3 mediated release of intracellular calcium and activation of cation channel

How taste developes

When mother during pregnancy or during lactation drinks or eats certain food, the aromatic components from the food are transferred to the fetus (during pregnancy) or the infant (during lactation) → influence of taste at young age

bitter suppression

suppressing bitter tastes: Aspartame > sodium salts

Stomach: mucus layer

protects wall of stomach against extreme environment in the lumen

• secreted by mucous (goblet) cells

• ° mucine = glycoproteins containing cysteine and O-linked and N-linked oligosaccharides

• low pH + protease activity

• Defence and repair: antimicrobial proteins (lysozyme) + trefoil peptides (acid and enzyme resistant)

Stomach: epithelial wall

Mucosa / Mucous membrane

Large folds

• smoothened when the stomach is filled with food

Foveolae/gastric pits

• between folds

• grooves with exits for the different glands

• Mucous cells

  • produce mucine

Gastric glands

• Chief cell/ zymogen cells

  • produce enzymes (pepsinogen + lipase)

• Parietal cells

  • excrete HCl

  • use high amounts of energy

  • secrete the intrinsic factor that enables the absorption of vitamin B12 by the small intestine, otherwise B12 would be destroyed by stomach acid

• ECL cells = Enterochromaffin-like cells

  • situated near parietal cells

  • aid in production of HCl by release of histamine

Summary secretion of each part stomach

Origin	Secrete
Goblet cells/ mucous cells	mucines
Gastric chief cells	pepsinogen and lipase
Parietal cells	HCl and intrinsic factor (vitamin B12)
Gastric enteroendocrine cells (pylorus) = Enteroendocrine G cells	gastrin

HCl production by parietal cells

1) A chloride-bicarbonate transporter in the basal membrane supplies Cl- which is released in cotransport with K+ by a KCl transporter at the apical membrane

2) H+ (produced by carbonic anhydrase) is released in the stomach lumen by an H+/K+- ATPase

Rules:

• Na+ is always extracellular —> easy transport to intracellular

• K+ is always intracellular —> easy transport to extracellular + can take Cl- with him

Gastrin

stimulates the movement of the corpus and release of hydrochloric acid

pylorus produced more gastrin when the wall is more stretched

Cell renewal in stomach

by displacement of non-differentiated cells of the corpus zone, which have high mitotic activity

cells	age	replaced by…
mucus-producing cells	4 days	non-differentiated cells
mucosal neck cells, the zymogen head cells, wall cells	/	non-differentiated cells
head and wall cells	few months	non-differentiated cells

when small defects arise: non-differential cells originate again from differentiated cells and epithelium is covered in extra mucosal layer

fecal particle size depends on:

• SCFA (= Short Chain Fatty Acids) production

• residence time

• microbiome diversity

Small intestine

= site of enzymatic digestion

Wall composition (outside → inside)

• serosa

• muscularis externa

• submucosa

• inside mucosa

  • Crypts of Lieberkühn

  • Enlargen absorption surface

    • circular folds of Kerkring

    • villi

    • microvilli

duodenum => secretion

• epithelial cells = glands of Brühner near Crypts of Lieberkühn → secrete intestinal juice

• Liver → secretion of bile (concentrated by absorption of water and salts)

• pancreas → secretion of enzymes (proteases, lipases, carbohydrases)

jejenum => absorption

reabsorption => ileum

Large intestine

= site of microbial fermentation

• no villi, but monolayeer of cylindrical apithelium consisting of mucusproducing cells and enterocytes with short microvilli

ascending

transverse

descending

Villi

• absorbing cells

• mucus secreting cells

• layer of microvilli containing polysaccharide fibers = Glycocalyx

Why is it important that the mitotic activity of non-differentiated stem cells in the crypts is not disturbed?

• lifespan of inestinal ephithelium villi = 2 to 3 days

• Reduction of turnover (e.g. infection, bad nutrition) → leads to shorter villi and reduces absorption

• people suffer from malabsorption of food because of a reduced intestinal surface

GALT (What? Composition? Function?)

= Gut Associated Lymphoid Tissue

• immune system of the intestine

Composition

• ephithelial M-cells

• macrophages

• dendritic cells (DC)

• B- and T-lymphocytes

Function

• Immuno-exclusion = preventing uptake of MO and toxins

• Immuno-elimination = neutralization of antigens during infection

• Immuno-regulation = making a distinction between nutrients and potentially hazardous antigen

Involved in

• inflammatory bowel disease

• colorectal carcinogenesis

GALT - small intestine vs large intestine

Small intestine	Large intestine
Peyer’s patch Discontinuous mucus layer Paneth cells enriched in crypts of mucus layer: secrete antimicrobial peptides (AMP)	Isolated lymphoid follicles (ILF): respond to epithelium derived cytokine signals ans produce interleukins Goblet cells produce thick mucus layer of glycoproteins with trefoil factors

s-IgA

= secretorial immunoglobine-A

• complex of IgA + secretory component

• resistant against hydrolysis

• secreted in intestinal lumen

Caco-2 cell

• cultured in monolayer with microvilli + expression of small intestinal enzyme activities on the apical side

• tight junctions between cells

• semi-permeable filter support → more free access of ions and nutrients on both apical and basal sides of the monolayer

growth intestine

= defense mechanism against colon cancer

• paneth cells stay in the crypt base with stem cells

1) stem cells produce organoids (= self-renewing intestinal ephithelia = Transit-amplifying cells)

2) TA cells proliferate rapidly and move up the walls of the crypt

2) As cells move upwards they begin to differentiate into goblet cells and enterocytes

3) Differentiated cells reach the villa → apoptosis → cells are shed into the lumen of the small intestine

Migration → cell death: 3 - 4 days

Movements stomach

During eating

• Peristaltis = alternating contraction and expansion of circular and longitudinal muscle layer

• Segmentation = rhythmic contraction of circular muscle layer

Between meals

• Interdigestive migrating motor complex (MMC) = makes sure that all remaining food in the stomach and small intestine is transferred to the large intestine → interrupted after the intake of a meal

Trajectory food from esophagus to stomach (from discontinuous eating → continuous digestion)

1) upper sphincter relaxes + epiglottis prevents access to trachea

2) peristaltic movement to the stomach

3) Entering the stomach

• adaptive relaxation: corpus and fundus relax = prevents the pressure in the stomach to become too high and the feeling of satiation to occur too fast when the stomach contents during meal increases

• postprandial phase: peristaltic wave in the antrum + closure of the pylorus → food fragments are mixed with gastric juice

• Smaller particles can pass and arrive gradually in the duodenum

• Cardia: welcomes the food coming from the oesophagus via peristaltic movements

• Fundus + Corpus: relax when food enters the stomach to prevent too high pressure and early satiation (adaptive relaxation)

• Antrum: peristaltic movements around the food and release of gastric juices

• pylorus: transition from stomach to intestine

Ileal brake

= When not absorbed fat reaches the ileum → reflex inhibits further emptying of the stomach

Gastro-colic reflex

increasing contractions in the colon when food enters the stomach to make place for new food

Tracers

= easily identifiable components that behave in the same way as the examined material and do not noticeably influence the characteristics of the unit under examination

isotope method

• 13C-tracer is absorbed in the small intestine after which it participates in respiratory metabolism to produce 13C-CO2 which is excreted in expired air

• in solid and liquid meal

Endogenous hydrolic digestion (purpose, regulation, enzymes, barriers)

= hydrolysis by enzymes

Purpose

• high molecular compounds → low molecular compounds (water soluble)

Regulation

• pH (acid predigestion vs alkaline digestion) → activation of inactive form of the enzyme prevents autolysis

• ions 

• Temperature

Main enzymes

• proteases/peptidases

• carbohydrases

• lipases

Barriers that need to be passed

1) The mucuslayer: diffusion of hydrophilic components

2) The apical membrane of the enterocyte: hydrophobic

3) The enterocyte

4) The basal membrane of the enterocyte: hydrophobic

Proteases/ peptidases

Location

• stomach

• small intestine

Autolysis

• to avoid autolysis proteases are secreted as inactive zymogens which are activated in the lumen 

Endopeptidases

• aromatic AA

  • pepsin

  • chymotrypsin

• basic AA

  • trypsin

inactive zymogen	location activation	protease
pepsinogen	stomach	pepsin
trypsinogen chymotrypsinogen	pancreas, by: enterokinase trypsin	trypsin chymotrypsin

Exopeptidases → clave AA from C- or N-terminal of oligopeptides

• NH2 (glycocalyx)

• COOH (pancreas)

inactive zymogen	location activation	protease
procarboxypeptidases	intestinal lumen	carboxypeptidase
aminopeptidases	intestinal epithelium	aminopeptidases + dipeptidases

Transport of dipeptides to bloodstream

1) absorbed in the enterocyte by non-selective peptide transporters (PEPT1 and PEPT2 = symporters of H+)

2) Hydrolysed by intracellular peptidases 

3) Active uptake to the bloodstream by the influx of Na+ (energy provided by ATP)

pinocytosis/ paracellular transport

during periods of specific needs some larger peptides and even proteins may enter the bloodstream intact

(e.g. pregnancy, lactation, infancy)

Carbohydrases

Amylase

• starch: amylose (linear) + amylopectin (branched) → dextrin → maltose

• alpha (animal) vs beta (plant)

• require Cl- and light alkaline environment

• saliva = ptyalin (alfa-amylase): hydrolyses alfa-1,4 bonds in starch

Glycosidases

• Maltase/sucrase(invertase)/lactase

• = extracellular glycosidases

• dissacharides → monosacharides (glucose, fructose, galactose)

Isomaltase

• adhered to sucrase → sucrase-isomaltase

• hydrolyses alfa-1,6 bounds in starch (branches)

Transport to enterocyte

• glucose/ galactose: SGLT1 (= sodium-glucose transport protein-1) + parallel influx of Na+ with energy use

• fructose: GLUT5 by facilitated diffusion → only a proportion of fructose can be absorbed + the remaining stays in the lumen causing osmotic diarrhea or is changed to lipids (= liver fattening

Transport to blood

• Glu,gal and fru use the same transporter: GLUT2

Lipases

Characteristics

• less substrate specificity

• primary alcohol groups → beta or 2-monoglyceride and FFA

• lipolysis occurs in stomach

• pancreatic enzyme secreted in the duodenum

Steps

1) pancreatic lipase:

• bile salts: emulsify fat

• Ca and co-lipase: break down bile salts + hydrolyse triglycerides

2)

• triglycerides → fatty acids → micelle formation → monoglycerides and FFA’s are absorbed

• bile salts are absorbed in ileum → transport via portal vein → liver → reused in gall-bladder

3) in enterocyte

• FFA’s and monoglycerides → co-enzyme A esters of FFA (requires energy) → triglycerides

• triglycerides packed in chylomicrons (= lipoproteins) → tranpsorted to lymphatic system → taken up in blood stream

Gastro-intestinal peptides / hormones

Hormone	Target organ	Action	Stimulus
Gastrin	Stomach	Secretion HCl Motility ↑	Filling of the stomach
CCK-PZ	Gall bladder, pancreas	Contraction, secretion pancreatic juice/ bile salts	FA and AA in duodenum
Secretin	Pancreas, stomach	NaHCO3 ↑ stomach motility↓	Food in stomach and intestine
GIP	stomach, intestine	Intestinal juice ↑, motility ↓	CH and fat in duodenum

Humans/ MO interaction: competitive/fermentative model of digestion

1) humans digest the food according to competitive model

2) residues are fermented by MO in storage organ after stomach and small intestine (= colon): use food substances and nitrogen sources in anaerobic way

composition microflora: how is it determined?

1) The host

• specificity adhesion and absorption capacity

• rate of secretion and composition

• motility in the intestine, frequency and amount of feed uptake

2) The food

• form

• composition

• contamination

3) The MO

• specificity adhesion → determines which MO can succesfully colonize the colon

• growth factors

• enzymes

Types of MO

1) Useful bacteria

• Lactobacilli

• Streptococci

• Enterobacteriaceae

• Bacteroïdes

2) Pathogens

Microbial pathways in the colon: carbohydrate metabolism

What: food polysaccharides

• ERS = enzyme-resistant starch (alfa-bound hexose)

• NSP = non-starch polysaccharides (beta-bound hexose)

reductive acetogenesis: H2 → acetic acid

sulfate reduction: H2 → H2S

Microbial pathways in the colon: N-metabolism and microbial growth

protein → non-protein compounds (peptides, AA and NH3) → N-sources for microbial growth

Fermentative activity in the colon (order)

1) carbohydrates are broken down

2) protein fermentation starts to dominate when carbohydrate reserves are depleted → protein breakdown products (phenols, amines, ammonia) → negative for colon health (cancer)

Solution: remove tumor part in wall and replace by stem cells → redesign the wall

Characteristics of axenic/gnotobiotic animals

General

Axenic animals

• improved turnover of feed and reduced peristaltis

• alterations in morphology and contents intestine

• no lactic acid and lactase

• higher losses of urea and endogenous N

• no branched and less saturated FA in faeces

• Only conjugated primary bile acids in faeces

• Possible deficit of vitamins B and K

• More efficient intestinal absorption (antibiotics)!

Gnotobiotic animals

• microflora is completely identified according to the accepted standards

Probiotics

= live MO that, when administered in sufficient quantities, confer a health benefit on the host

Examples

• Bifidus

• Lactobacillus

• Faecalibacterium prausnitzii

• Akkermansia muciniphila