NBA3 (Molecular aspects of) carbohydrate + lipid digestion and absorption
27 important questions on NBA3 (Molecular aspects of) carbohydrate + lipid digestion and absorption
What is the lipid classification?
- fatty acids
- eicosanoids
- triacylclylcerols (fats and oils)
- Waxes
- ceramides --> sphingolipids
- cerebrosides
- gangliosides
- other glycolipids
- Glycolipids
- glycero-phospholipids
- plasmalogens
- phosphatidates
- phospholipids
- steroids
- fat-soluble vitamins
- other terpenes
What is the dietary lipid composition?
- >95% triglycerides (neutral fats; 95g)
- cholesterol, cholesterol-esters
- phospholipids
- unesterified fatty acids
- fat soluble vitamins
very efficiently absorbed (95-97%)
What are the basics of digestive and absorptive processes?
- Most nutrients must be digested before they can be absorbed
- Nutrient digestion occurs both in the lumen and on the brush border
- Digestion is accomplished through enzymes from the mouth, stomach, pancreas, and small intestine and with the help of bile from the liver
- Once digested, nutrients must move into the cells of the gastrointestinal tract (absorption)
- Digestion already starts in mouth, almost all absorption of nutrients occur in small intestine
- Nutrient absorption is fast (most within 30 min)
- Feedback: unabsorbed food ileum slows down transit ("ileal break")
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What are the most common molecular structures of fatty acids?
- Stearic acid (18:0)
- Cis-oleic acid (18:1omega9)
- Elaidic acid (trans 18:1omega9)
- Linoleic acid (18:2omega6)
omega is de kant waar niet the O=OH zit
What are the absorption sites?
- Stomach
- Duodenum
- Jejunum
- Ileum
- Large intestine
What are the 4 primary mechanisms for nutrient absorption?
- Diffusion
- Facilitated diffusion
- Active transport
- Pinocytosis
How are lipids digested with lipases
- Key enzymes in lipid digestion
- Secreted in mouth (lingual lipase) and stomach (gastric lipase; optimal for low pH)
- responsible for ±10%-30% of digestion of TG
- prefer medium/short chain FA, sn-3 position (milk)
- Major: pancreatic lipase (PL)!
What is the carbohydrate classification?
- carbohydrates
- simple carbohydrates
- monosaccharides (1 sugar unit)
- disaccharides (2 sugar units)
- complex carbohydrates
- oligosaccharides (3-10 sugar units)
- polysaccharides (>10 sugar units)
lactose --> glucose + galactose
sucrose --> glucose + fructose
maltose --> glucose + glucose
trehalose --> glucose + glucose
Raffinose + stachyose + verbanese --> difficult to digest flatulence
How are lipids digested with emulsification, micelles, PL and colipase?
- Duodenum: pH 6-7 (optimum for PL)
- Emulsification and micelle formation are required for proper digestion and absorption (enhance
s surface area)
- PL works beast at oil-water interface
- Specificity: sn-1 > sn-3 bonds
- Orlistat, inhibitor of GL & PL, to reduce absorption of TG
- minor effect: 30% inhibition, but only ±5% weight reduction
- lipid droplets are coated on their surfaces with bile salts and phospholipids
- ... But these inhibit binding of PL...
- Requirement of cofactor: colipase
- Pancreatic fluid, pro-enzymes
IMAGE
What are glycosidic bonds?
- Covalent bond that joins 2 sugar molecules
- alfa- and beta-glycosidic bonds: stereochemistry
- number: position linked
- amylose (alfa (1-4)
- amylopectin (alfa (1-6) (at branch points) and alfa(1-4)) (plant based)
- glycogen (alfa(1-4) and alfa(1-6) (animal based) (more branch points than in amylopectin))
How are polysaccharides digested?
- glycosides specific for hydrolysis of alfa(1-4) glycosidic linkages
- beta(1-4) bonds (cellulose, lactose), and alfa(1-6) linkages (amylopectin) are resistant to this enzymes
- persent in saliva and pancreatic juice
How are disaccharides digested?
- Maltase breaks maltose (alfa(1-4)) into two glucose molecules
- Isomaltase breaks isomaltose (alfa(1-6)) into two glucose molecules
- Sucrase breaks sucrose (alfa(1-4)) into one glucose and one fructose molecule
- Lactase breaks lactose (beta(1-4)) into one glucose and one galactose molecule
- Trehalase breaks trehalose (alfa(1-1) into two glucose molecules
Nearly all dietary starches and disaccharides ultimately are hydrolysed completely by specific glycosidases to their constituent monosaccharide units
How are phospholipid and cholesterol-ester digested?
phospholipid
lecithin ---phospholipase A2---> fatty acid + lysolecithin
cholesterol ester ---cholesterol esterase---> cholesterol + fatty acid
What are the (partial) products of lipid digestion from micelles?
- 2-monoacylglycerols
- lysolecithin
- cholesterol
- fatty acids
- micelles: polymolecular aggregates; smaller
diameter (±50-80nm) than unhydrolyzed precursor particles
- this allows them access to the intramicrovillus spaces (50-100nm) of the intestinal membrane
- without bile acids only ±50% (not 95%) lipid absorption occurs
Lipid digestion and mixed micelle formation -->
calcium
What do you know about lactose intolerance?
- Lactose (beta(1-4) linkage) is degraded by lactase
- Lactase is high in infants, declines after weaning in most mammals
abdominal pain, cramping, distention, flatulence, diarrhoea, nausea, vomiting
What is the solubility of fat digestion products in bile salt solution?
2-monoglyceride and fatty acid (partly ionised) have a high solubility
diglyceriden and triglyceride have a low solubility
bile salts need to be present!!
How does the uptake of FAs and monoaclglycerides into the enterocytes go?
- Micellar particles are sufficiently water soluble to penetrate the unstirred water layer that bathes the enterocytes of the small intestine
- Micelles are small enough to interact with the microvilli at the brush border, whereupon their lipid contents more into the enterocytes
- this is thought to be driven by a concentration gradient (FA sink; FABP)
Sites of sugar absorption along the crypt-villus axis
Villius region [SGLT1; GLUT-2; GLUT-5]; crypt region
The molecular and cellular mechanisms of intestinal lipid absorption
- NPC1L1
- APO-B48 --> chylomicron
- mixed micelles
- CD36 + FABPpm
- FATP4
- TG --> APO-B48 --> chylomicron
- portal vein
chylomicron are secreted into the lymph fluid before coming to the liver.
ABCG5/GB transports Ch back into the lumen
What is the cellular fate of glucose?
- 60% via GLUT2 (into blood)
- 25% diffuses into blood
- 15% leakage to lumeen
- + energy for enterocyte
What is needed for the absorption of fructose?
- Mediated by GLUT5
- Only 60% absorbed, malabsorption > 50g/d (diarrhoea, gas, bloating)
What are medium chain triglycerides (MCTs)?
- Chain length fatty acids of 6-12 carbon atoms
- small amounts in diet, but high therapeutic value as supplements in patients with GI disorders
- Digestion and absorption diggers with that of long-chain TG:
- more rapid hydrolysis by lipases
- more water-soluble
- efficiently taken up by enterocytes, even without bile salts present
- within enterocytes, no need for resynthesis and chylomicrons
- secretion directly into portal circulation
- rapid source of energy!
What is the metabolism of monosaccharides
- Once absorbed, most go to liver
- Fructose and galactose converted into glucose
- Some reaches peripheral circulation --> insulin
- Deposited into tissues (muscle (500g), liver (100g) [glycogen], adipose cells [TG]
What are the new insights in fructose metabolism and the role of the small intestine?
- Isotope tracing reveals that the small intestine metabolites most dietary fructose
- High-dose fructose saturates intestinal fructose clearance capacity
- Excess fructose spills over to the liver and colonic microbiota
- Intestinal fructose clearance is enhanced by feeding
What are the glycemic responses to carbohydrates?
Rational: the rate at which glucose is absorbed from the intestinal tract appears to be an important parameter in controlling the homeostasis of blood glucose, insulin release, obesity, and possible weight loss.
Estimated glycemic load = 15 [typical target total is 100/day of less]
What happens with TAG after absorption?
- enterocytes convert long-chain fatty acids back into triglycerides within the smooth endoplasmic reticulum
- These are then complexed with apoproteins, after which chylomicrons are formed
- These are transported across the basolateral membrane by exocytosis, enter
the lymph system that drains into the venous system (bypasses the liver!)
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