Absorption 2: Nutrients Flashcards
what is the % of polysaccharides in our diet?
what are the diff kinds?
~45-60% of dietary carbohydrate is in the form of starch which is a polysaccharide:
Starch: a storage form of carbohydrates that is found primarily in plants. It consists of amylose and amylopectin
Amylose: straight-chain glucose polymer that typically contains multiple glucose residues, connected by α-1,4 linkages
Amylopectin: branched glucose polymer, therefore contains both α-1,4 + α-1-6 linkages
Glycogen: the storage form of carbohydrates for animals. Like amylopectin (α-1,4 + α-1-6 linkages), but more highly branched
what is the % of disaccharides in our diet?
what are the diff kinds?
30-40% of dietary carbohydrates are disaccharides - sucrose and lactose
Sucrose: made up of fructose + glucose
Derived from sugar cane/sugar beets
Lactose: made up of glucose + galactose
Found in milk
what is the % of monosaccharides in our diet?
what are the diff kinds?
Remaining 5-10% of dietary carbohydrates are monosaccharides - Fructose and glucose
There is no evidence of any intestinal absorption of either starches or disaccharides -
the SI can only absorb monosaccharides - all dietary components must be digested to monosaccharides before absorption
digestive process for dietary carbohydrates is a two-step process, what are the 2 steps?
- Intraluminal hydrolysis of starch to oligosaccharides by salivary and pancreatic amylases
- Membrane digestion of oligosaccharides to
monosaccharides by brush-border disaccharidases.
what is Luminal Digestion (step 1)?
Involves the action of salivary amylase and pancreatic amylase
Both salivary and pancreatic acinar cells (when stimulated by CCK and Ach) synthesise and secrete active α amylases
Salivary amylase in the mouth initiates starch digestion, however this is inactivated by gastric acid
So, can’t participate in luminal hydrolysis
Pancreas is stimulated by CCK to produce Pancreatic α amylase which then completes starch digestion in the lumen of SI
Amylase is an endoenzyme (work within the polymer chain) that hydrolyses internal α-1,4 linkages
It does not cleave terminal α-1,4 linkages, α-1,6 linkages (i.e. branch points) or α-1,4 linkages that are immediately adjacent to α-1,6 linkages
Starch hydrolysis culminates in maltose, maltotriose + α-limit dextrins (contain alpha 1-6 linkage) (all non-absorbable)
Further breakdown of these products into monosaccharides is required
what is Membrane Digestion (jejunum) (step 2)?
This is the hydrolysis of oligosaccharides to monosaccharides by brush-border disaccharidases
The human small intestine has 3 brush-border oligosaccharidases which are all membrane proteins:
Lactase
Maltase
Sucrase-isomaltase (made up of 2 enzymes: sucrase + isomaltase)
Action of these enzymes:
Lactase has only one substrate, lactose which is broken down into glucose and galactose
Maltase can also degrade the α-1,4 linkages in straight-chain oligosaccharides to yield glucose (converts maltose into glucose)
Sucrase can split sucrose into glucose and fructose
Maltase, sucrase-isomaltase will all cleave the terminal α-1,4 linkages of maltose, maltotriose and α-limit dextrins
Isomaltase is the only enzyme that can split the branching α-1,6 linkages of α-limit dextrins
Peak oligosaccharidases distribution and activity occur in the proximal jejunum
Considerably less activity is noted in the duodenum and distal ileum
No activity in the large intestine
describe the 2 step process in which glucose, galactose and fructose (monosaccharides) are absorbed by the SI?
Through the actions of these enzymes you end up with a lot of glucose and some fructose and galactose!
Glucose, galactose and fructose are then all absorbed by the small intestine in a two-step process:
1. Uptake across the apical membrane (brush border) into the epithelial cell:
Na/glucose transporter SGLT1 is responsible for glucose + galactose uptake at apical membrane
This is active transport because glucose influx occurs against glucose concentration gradient → energized by the electrochemical Na+ gradient, which is maintained by the extrusion of Na+ across the basolateral Na-K pump
Na+-driven glucose transport is an example of secondary active transport
Apical fructose transport is via GLUT5 transporter (facilitated diffusion)
Exit of these monosaccharides across the basolateral membrane
This is done using a facilitated sugar transporter - GLUT2 (for all 3 monosaccharides)
what is lactase deficiency?
who does it affect?
Primary lactase deficiency is extremely common → 3% White Caucasians (low), 55% Asian, 82% Afro-Caribbean
After weaning the lactase levels decrease.
Historically in cultures where cattle farming did not exist, lactase deficiency is prevalent
When individuals from these cultures now ingest lactose usually in the form of milk/milk products it is associated with a range of gastrointestinal symptoms, including diarrhoea and cramps
what happens to plasma concentrations in lactase deficiency?
In individuals with primary lactase deficiency, the ingestion of lactose:
Results in a much smaller rise in plasma [glucose]
Colonic bacteria metabolise non-absorbed lactose in colon → releasing H2
H2 absorbed into blood and excreted by lungs → breath H2 ↑
Breath hydrogen is used as a indicator that if someone that has lactase deficiency
Treatment: Decreasing or eliminating milk/milk products from diet or using milk products treated with a commercial lactase preparation
In individuals with primary lactase deficiency, the ingestion of lactose - Much smaller rise in plasma [glucose]
how are proteins digested?
protein sources?
Proteins are first digested into their constituent oligopeptides and amino acids before enterocyte uptake
Exceptions:
Antigenic amounts of dietary protein are absorbed intact in the gut,
Neonates can absorb substantial amounts (up to 6 months) of intact protein from colostrum (1st form breast milk) through endocytosis
Protein sources are:
- Dietary (50%)
- Endogenous (50%) (enzymes, hormones, desquamated cells etc.)
what are the 4 major pathways by which digestion and absorption of proteins happen?
The digestion and absorption of proteins can occurs through four major pathways.
1. Luminal proteases produce by stomach/pancreas hydrolyses proteins to peptides and to amino acids, which are then absorbed by enterocytes
2. Luminal proteases digest proteins to peptides, but enzymes present at the brush border digest the peptides to amino acids, which are then absorbed
3. Luminal enzymes digest proteins to peptides, which are taken up as oligopeptides by the enterocytes → further digestion of oligopeptides by cytosolic enzymes yields intracellular amino acids, which are moved by transporters across the basolateral membrane into the blood
4. Luminal enzymes digest dietary proteins to oligopeptides, which are taken up by enterocytes and are moved directly into the blood
how are gastric and pancreatic proteases produced?
Luminal digestion of protein involves both gastric and pancreatic proteases → yielding amino acids and oligopeptides
Both gastric and pancreatic proteases are secreted as pro enzymes
Gastric Proteases
Gastric chief cells secrete pepsinogen which is activated to pepsin by a low intragastric pH
Pepsin is an endopeptidase (digests within chain) with primary specificity for peptide linkages of aromatic and larger neutral amino acids
Although pepsin in the stomach partially digests 10-15% of dietary protein, pepsin hydrolysis is not absolutely necessary due to pancreatic proteases.
Pancreatic Proteases
5 pancreatic enzymes (for protein digestion) are secreted as inactive proenzymes (zymogens).
When they end up in SI trypsinogen comes into contact with enterokinase to form trypsin which then autocatalytically cleaves all other enzymes to their active form.
what are exopeptidases and endopeptidases?
Pancreatic proteolytic enzymes are either exopeptidases or endopeptidases:
Endopeptidases (Trypsin, chymotrypsin + elastase) have an affinity for peptide bonds adjacent to specific amino acids, producing of oligopeptides with 2-6 amino acids
Cleave within the peptides
Exopeptidases (carboxypeptidase A and carboxypeptidase B) hydrolyse peptide bonds adjacent to the C-terminus (can be N-terminus), releasing individual terminal amino acids
Cleave at the ends of peptides to liberate the AA.
The coordinated action of these pancreatic proteases converts approximately 70% of luminal polypeptides to oligopeptides + ~30% become free amino acids
what are brush border peptidases?
Multiple peptidases are present the brush border of villous epithelial cells
Small peptides post-luminal digestion undergoes further hydrolysis by these brush border peptidases to form amino acids
Enterocyte apical transporters can take up small oligopeptides and once inside the cell they may be further digested by cytoplasmic peptidases
Brush-border peptidases have affinity for relatively larger oligopeptides (3-8 amino acids)
Like pancreatic proteases, each of the several brush-border peptidases is either an endopeptidase, an exopeptidase, or a dipeptidase and has affinity for specific peptide bonds.
Exopeptidases can be either C-or N terminal peptidases to release terminal aa’s.
Diagram:
30% AA
70% Oligo-peptides
Oligopeptides further digested by brush border peptidases e.g. AA4 –> AA3 –> AA2
How are individual brush border amino acids transported?
Epithelial amino acid transport systems and their mediators
The type of amino acid will determine how it is absorbed into the enterocyte.
- Transport activity for cationic amino acids + cystine → designated system b0,+
This involves using a Na+-independent transporter.
This is an Antiporter which couples the uptake of cationic amino acids and cystine to the efflux of neutral amino acids - Transport activity of neutral amino acids - designated system B0
This involves using a Na+-dependent transporter
This system mediates the uptake of all neutral amino acids - The transport of glycine and proline is mediated by the Na+-dependent IMINO system and the H+-dependent IMINO acid carrier.
- The transport activity for anionic amino acids was named system XAG (EAAT3), a Na+-dependent transporter for aspartate and glutamate.
The enterocyte uses ~10% of the intracellular AAs for protein synthesis.
The disorders above are autosomal recessive which effect the below transporters.
If you have one of the disorders it means you can’t absorb those particular classes of AA.
However the cell can still absorb these AA via the mechanism discussed previously – PEPT1 (oligopeptides are absorbed which contain lots of different types of AA) – this can compensate for the disorders).
how do amino acids enter the enterocyte?
Amino acid efflux from enterocyte:
Amino acids enter the enterocyte from either 2 processes:
Within the enterocyte multiple amino acid transport processes on basolateral membrane mediate amino acid exit from enterocyte into blood:
- Release of cationic amino acids mediated by heteromeric antiporter 4F2hc/y+LAT1
- Net efflux of neutral amino acids occurs via 4F2hcindependent LAT transporters of the SLC43 family
what can defects in apical amino transport cause?
Defects in apical amino transport:
Hartnup disease and cystinuria are autosomal recessive disorders of apical membrane amino acid transport
Hartnup disease:
Absorption of neutral amino acids by system B0 in the SI is markedly reduced
NB: oligopeptides containing neutral amino acids are absorbed normally in Hartnup disease
Clinical signs most evident in children → skin changes of pellagra, cerebellar ataxia + psychiatric abnormalities
Cystinuria:
As a result of this condition Cysteine + basic amino acid import by system B0+ or b0+ is abnormal
NB. absorption of oligopeptides containing basic amino acids is normal
Clinical signs: formation of kidney stones
The lack of evidence of protein deficiency in either disease suggests more than one transport system for different amino acids, as well as a separate transporter for oligopeptides!
how is fat absorption crucial to health?
Fats are the predominant energy source in the fasted state
The vast majority of our stored energy is in the form of adipose tissue (protein - glycogen)
Lipids are the most concentrated depot of energy storage:
Represents ~9.4 kcal/g
Contain 2x at much energy per gram than glycogen or protein
Non-polar which means they can be stored in an anhydrous state
1g dry glycogen has to bound to 2g of water as it is polar (not efficient)
Therefore they have evolved to be the storage depot of choice
how is fat distributed?
Most of the body’s fat depots exist in the subcutaneous adipose tissue layers
Fat also exists to a small extent in muscle
Fat can exist in visceral depots (obese/older people)
Visceral fat is more metabolically active
It is also associated with cardiovascular disease
Therefore, visceral fat is more dangerous to health than subcutaneous fat, therefore BMI is not always indicative of someone’s health
Typical 70-kg human carries about 15 kg of fat (compared to only 190g of glycogen)
555,000 kJ of energy stored in adipose tissue which theoretically can sustain the body’s entire resting metabolic requirement for in excess of 50 days
what is vitamin A important for?
lack of it results in..?
Vitamin A
Important for vision
Deficiency leads to → night blindness, corneal drying (xerosis), corneal degeneration, blindness (xerophthalmia), impaired immunity, hypokeratosis, keratosis pilaris.
Overdosing can occur as Vitamin A is fat-soluble. Therefore disposing of any excesses taken in through diet is much harder than with water-soluble vitamin. This can lead to hypervitaminosis A
Hypervitaminosis A: This can lead to → hair loss, nausea, jaundice, irritability, vomiting, blurry vision, headaches, muscle + abdominal pain
what is vitamin D important for?
lack of it results in..?
Vitamin D
Not really a vitamin as sunlight can generate Vitamin D3 in the skin of animals
Therefore individuals with adequate exposure to sunlight do not require dietary supplementation.
Form in skin is 7-dehydrocholesterol.
Sunlight converts this into VitmainD3
Vitamin D3 then undergoes further hydroxylation in the liver (25D3) and then in the kidneys to produce the active form 1,25D3
1,25D3 then binds to VDR and impacts on gene expression associated with proteins for calcium transport
Regulates calcium via calcium pumps + calbindin
1,25D3 then goes to the intestine which causes an increase in the absorption of calcium and phosphate
Dietary sources are in the form vitamin D3 (cholecalciferol)
Found in egg yolk, fish oil and a number of plants
Must be hydroxylated twice to 1,25-dihydroxycholecalciferol
Vitamin D3 deficiency can result from inadequate intake of D3 coupled with inadequate sunlight exposure. This leads to:
Impaired bone mineralisation → bone softening diseases, rickets in children and osteomalacia in adults, possibly contributes to osteoporosis
Vitamin D may also be linked to many forms of cancer, and important in cancer prevention e.g. higher VD, less likely to develop cancer.
what is vitamin E important for?
lack of it results in..?
Vitamin E
Otherwise known as tocopherol
There are 8 different forms, alpha-tocopherol most biologically active.
Most abundant food sources: vegetable oils - e.g. palm oil, sunflower, corn, soybean and olive oil.
Antioxidant - role in protection against cardiovascular disease and cancer
Vitamin E deficiency usually results in neurological problems due to poor nerve conduction.
what is vitamin K important for?
lack of it results in..?
Vitamin K
Found in various foods in the diet, and it is also produced by intestinal bacteria
Involved in the carboxylation of specific glutamate residues in proteins to form gamma-carboxyglutamate residues (abbreviated Gla-residues).
Gla-residues are usually involved in binding calcium.
14 human Gla-proteins have been discovered and they play key roles in regulation of 3 physiological processes:
Blood coagulation - risk of massive uncontrolled internal bleeding
Bone metabolism - cartilage calcification and severe malformation of developing bone
Vascular biology - deposition of insoluble calcium salts in arterial vessel walls
name a few essential fatty acids
what are their roles?
Fats are important sources of essential fatty acids.
Fatty acids are an essential dietary requirement because they cannot be derived endogenously
The following fatty acids are very important:
- Linoleic acid
- Linolenic acid
- Arachidonic acid
They are Important in cellular and organ processes:
- Production of Eicosanoids, e.g. prostaglandins
- Regulating immune and inflammatory responses
- Formation of healthy cell membranes
- Development and functioning of the brain and NS
- Responsible for regulating BP, blood viscosity, vasoconstriction,
what is dietary fat mainly and least made up of?
Of consumed dietary fat:
More than 90% is in the form of triglycerides, usually long-chain fatty-acyl esters of glycerol
~5% come from cell membranes and are therefore phospholipids
Most phospholipids are glycerolipids:
Esterified at the first 2 positions to fatty acids
Esterified at the 3rd position → phosphate
This phosphate is then esterified to a head group, i.e. phosphatidylcholine
These phospholipids are both hydrophobic and hydrophilic
The other major class of membrane phospholipid is the sphingolipid, which has a serine rather than a glycerol backbone
Also diet contains ~0.5 g of (un)esterified cholesterol
Total = 90% Triglycerides + 5% Phospholipids + <5% Cholesterol + lipovitamins
what is the main way to get energy from fat?
explain the steps
β-oxidation is the main pathway to liberate energy from fat (used in fasting periods)
Steps:
The majority of fat in our bodies is in form of triglycerides.
Triglyceride is broken down to 3 fatty acids
The fatty acids are primed to form fatty acyl-CoA using one molecule of ATP
Fatty acyl-CoA enters β-oxidation:
Oxidation step to produce energy in form of FADH2 (used in oxidative phosphorylation)
Hydration step
Oxidation stop to produce energy in form NADH+ (used in Oxidative phosphorylation)
1 cleavage step → Acetyl CoA (2 carbons) is cleaved off a fatty acyl-CoA.
The acetyl CoA can then enter Krebs’ cycle
Long fatty acids go through the cycle many times, each time becoming 2 carbons shorter. Therefore longer fatty acids liberate more energy
What prevents these lipid particles from coalescing?
Coating the emulsion droplets with: membrane lipids, biliary phospholipids + cholesterol, denatured protein, dietary polysaccharides, products of digestion (e.g. fatty acids and monoglycerides),
The polar (hydrophilic) groups of the phospholipids project into the water, allowing for the droplets to be miscible with aqueous environment
This also prevents coalescence of the emulsion particles because charged heads repel each other
Now the core of the emulsion particle is composed of non-polar lipids - fatty acid/triglyceride (non-polar hydrophobic tail), which also contains cholesteryl esters + other
what is the second step of the digestive processing of fats?
- Lingual and gastric lipase initiate lipid digestion → liberate fatty acids
In mouth: lipid digestion begins, mediated by lingual lipase (released by salivary glands)
In stomach: both lingual lipase and [gastric lipase (produced by chief cells in response to gastrin/Ach)] digest large amounts of lipid
Lingual + gastric lipase begin to break down triglyceride into diglyceride, releasing single free fatty acid
In stomach
The released medium/short-chain fatty acids are ionised at acidic gastric pH –> remain in solution –> passively absorbed across gastric mucosa into portal blood
The released Long-chain fatty acids however are NOT absorbed as they are insoluble at acidic pH –> remain in core of triglyceride droplets
You can therefore digest a reasonable about of fat this way → in healthy adults ~15% of fat digestion occurs in stomach
what is the function of co-lipase?
Like many other pancreatic enzymes, co-lipase is secreted in the pro- form (i.e. pro-colipase)
Activation is as normal by trypsin
Pancreatic lipase is active only at the oil-water interface of a triglyceride droplet.
Co-lipase is probably crucial in:
Acting as an anchor for the binding of the lipase
And/or by first forming a colipase-pancreatic-lipase complex that can then bind to the lipid interface
Therefore pancreatic lipase can then break down fat (either digest triglyceride or diglyceride within fat droplets) into 2-monoacylglyceride and fatty acids
what is the fourth step of the digestive processing of fats?
- Action of bile to stabilise and emulsify fat
Adsorption of biliary lipids and lipases onto Emulsion droplets now leaving stomach into SI
Many of the lipolytic products (such as monoglycerides, fatty acids, phosphatidylcholine) all act as additional emulsifiers
As surface triglycerides are hydrolysed, they are replaced by triglycerides from the core of the emulsion particle resulting in an ever-decreasing emulsion droplet
Fat droplets begin to bud off main droplet → forming multilamellar vesicles (several lipid bilayers). This occurs due to fatty acids, monoglycerides and bile salts building up on the surface
Addition of more bile salts to multilamellar vesicles → thins out lipid coating and coverts it into unilamellar vesicles (single-lipid bilayer) which are then converted into mixed micelles composed of bile salts and mixed lipids
All the time, fat is being digested by pancreatic lipase
what is the fifth step of the digestive processing of fats?
- Lipolytic products entering enterocytes
Barriers to overcome:
- The mucous gel layer that lines the intestinal epithelial surface
- The unstirred water layer
- The apical membrane
Short/medium-chain fatty acids:
Readily soluble in water
The diffusion of these monomers through unstirred water layer and into enterocyte is efficient.
As fatty-acid chain length ↑, solubility in water ↓ whereas its partitioning into micelles ↑
Short/medium chain just go straight into enterocyte
Long chain, stay in micelle, then through one of 3 processes below also enter
When the fatty acid/bile salt mixed micelles reach the enterocyte surface, they encounter a low pH generated by Na-H exchange at the brush-border membrane The fatty acids are protonated and leave the mixed micelle to enter the enterocyte by:
Non-ionic diffusion
Collision and incorporation of the fatty acid into the cell membrane
Novel evidence of active carrier mediated processes
After entry, remaining bile salts are absorbed at the terminal ileum and colon
They are redirected to the liver in the portal blood
This is known as the enterohepatic circulation
Bile acids are recycled 6-8 times a day
what is the sixth step of the digestive processing of fats?
- Fatty acids once in the enterocyte and re-esterification
Short/medium chain fatty acids diffuse straight into blood
Long-chain fatty acids are re-esterified back into triglycerides in the SER and are in the form of fat droplets.
The re-esterification to form triglycerides occurs within the SER, using either absorbed 2-MG or glycerol-3-phosphate as a substrate.
Apoproteins are synthetised in RER are transported to SER.
The Apoproteins then associate with the lipid droplets.
These are further processed through the Golgi to produce vesicles called Chylomicrons
Chylomicrons are fat drops coated in apoproteins
These chylomicrons are then exocytosed across basolateral membrane into lymph and then eventually into the blood.
what is the seventh step of the digestive processing of fats?
What happens to the exported chylomicrons?
After a meal, chylomicrons find their way to the endothelial surface of capillaries of select tissues.
Here they encounter lipoprotein lipase
This hydrolyses triglycerides in the chylomicrons to fatty acids + glycerol, leaving behind remnant chylomicrons
Products go to:
Fatty Acid + glycerol → muscle + adipose tissue (where fatty acid is then re-esterified)
Remnants → liver (hepatocytes) and are recycled
Chylomicrons are just one type of lipoprotein → others are VLDL, LDL + HDL
Lipid transport pathway can be exogenous or endogenous
