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Introduction
Principle of digestion
Digestion: Mechanical and chemical process in which food is broken down in the GI
tract, releasing many nutrients in forms the body can use.
1. Principle of change
2. Principle of wholeness
As a whole this represents overall more than 100 times the human genome, and
is called the ‘‘metagenome’’. Thus, the intestinal flora can be considered as
an ‘‘exteriorized organ’’ which contributes to our homeostasis with multiple
functions largely diversified.
The biological functions controlled by the intestinal flora are related to the
effectiveness of energy harvest, by the bacteria, of the energy ingested but not
digested by the host.
Among the dietary compound escaping to the digestion occurring in the upper
part of the human gastro intestinal tract, the polysaccharides constitute the
major source of nutrient for the bacteria.
A healthy intestinal flora provides a barrier between the epithelial cells of the colon and
pathogenic bacteria, known as colonization resistance. In other words, these probiotics
colonize the entire colon wall effectively reducing space for pathogenic bacteria to take hold
or even break through the intestinal wall.
These bacteria also synthesize certain vitamins, like B7, biotin, B12, folic acid and vitamin K.
In addition, the gut flora produces enzymes that are secreted into the epithelial cells of the
colon, allowing various bodily functions to take place.
The healthy bacteria within the intestines also create molecules for the brain, otherwise
known as metabolites. This contributes to healthy brain function, as healthy bacteria have an
effect on neurological function.
The intestinal flora receives its nutrients from mucin, a glycoprotein that is excreted by the
mucous membranes.
Bacteria also ferment indigestible carbohydrates, otherwise known as dietary fiber, like
pectin, cellulose and hemicellulose into short chain fatty acids. These fatty acids are a great
source of energy for the body and contribute to healthy epithelial cell proliferation.
Bacterial – Brain Connection: The gut flora also makes neurotransmitters like serotonin and
dopamine. It can therefore communicate with the brain and controls a large number of
processes within its realm. The gut has been considered the second brain, as it has more
neuron cells than the spinal cord. With that said, the next time you have a “gut feeling”, go
with it.
http://thescienceofeating.com/2017/06/28/gut-flora-holds-key-good-health-heres-keeps-
whole-body-healthy/
https://drjockers.com/6-steps-to-rebuild-gut-
flora-metabolism/
https://www.integrativepsychiatry.net/gut_bra
in_dysfunction.html
Metabolic functions
Colonic microoganisms also play a part in vitamin synthesis and in absorption of calcium,
magnesium, and iron.
Butyrate is almost completely consumed by the colonic epithelium, and it is a major source of
energy for colonocytes.
Acetate and propionate are found in portal blood and are eventually metabolised by the liver
(propionate) or peripheral tissues, particularly muscle (acetate).
Acetate and propionate might also have a role as modulators of glucose metabolism:
absorption of these short-chain fatty acids would result in lower glycaemic responses to oral
glucose or standard meal—a response consistent with an ameliorated sensitivity to insulin.
In fact, foods with high proportion of non-digestible carbohydrates all have a low glycaemic
index. However, results of one study showed no effect of colonic fermentation of
carbohydrates on insulin resistance.
Trophic functions
All three major short-chain fatty acids stimulate epithelial cell proliferation and
differentiation.
However, butyrate inhibits cell proliferation and stimulates cell differentiation in epithelial
cell
The intestinal mucosa is the main interface between the immune system and the
external environment. Thus, that gut-associated lymphoid tissues contain the largest
pool of immunocompetent cells in the human body is not surprising.
The dialogue between host and bacteria at the mucosal interface seems to play a
part in development of a competent immune system.
The large intestine (cecum, colon and rectum; primarily the colon)
is involved in the absorption and secretion of electrolytes and water.
Enterocytes possess an array of transporters and ion channels . The sodium-potassium ATPase, is located on the basolateral membrane (the
‘blood side’) and transports the sodium ion outside the cell in exchange for the potassium (3Na+ to every 2K+ ions). This creates a sodium
concentration gradient, and hyperpolarizes the membrane, increasing the intracellular negative potential and driving the passive transport
systems (and thus transcellular ion transport). Moreover, transport of sodium (and chloride) is accompanied by passive transport of water, which
is both paracellular (through the tight junctions) and transcellular (by membrane water transporters, the aquaporins).
Sodium co-transporters are a common mode of intestinal transport
Sodium co-transporters transport the sodium ion together with another molecule (Fig. 10.2A). For instance, glucose is absorbed
together with sodium by the sodium-glucose co-transporter present in the luminal membrane, known as SGLT-1 (Sodium/Glucose
Linked Transport-1). Glucose is subsequently extruded into plasma at the basolateral membrane by theGLUT2 transporter (Fig.
10.7 below). The discovery of the link between intestinal transport of sodium and glucose had enormous clinical consequences. It was
during a cholera epidemic in Manila, in the late 1960s, that researchers observed that patients who had been dehydrated because of
diarrhea did not absorb oral sodium chloride well during attempts at oral rehydration. However, they started to do so when glucose
was also provided. This observation led to the formulation of the WHO oral rehydration solution, which subsequently saved the lives
of millions of children affected by severe diarrhea worldwide.
Other modes of sodium transport are the electroneutral (Fig. 10.2B) and electrogenic transport
The electroneutral sodium transport is through sodium/hydrogen exchanger (NHE), usually combined with chloride transport via the
chloride/bicarbonate exchanger known as AE exchanger (Fig. 10.2C). The exchangers are present on both luminal and basolateral
membranes. This type of transport is responsible for most of the sodium chloride reabsorption in the colon. In the distal colon the NHE
exchanger is upregulated by glucocorticoids.
The electrogenic absorption of sodium occurs through the epithelial sodium channels (ENaCs, also known as amiloride-sensitive
sodium channels), which are present on the luminal side of the epithelium (Fig. 10.2D). ENaCs are regulated by steroids (aldosterone)
and are important particularly in the distal colon. Absorption of Na+ is accompanied by Cl− following through a chloride channel (which
could be the CFTR – see below). Aldosterone also upregulates the Na+/K+-ATPase.
Chloride transport: the cystic fibrosis transmembrane conductance regulator (CFTR)
Luminal secretion of chloride occurs via the cystic fibrosis transmembrane conductance regulator (CFTR; Fig. 10.2B). The CFTR is a
single-polypeptide membrane ion channel. It is also present in the epithelia of the lung and sweat glands. Its function is controlled by
the G-protein–cAMP-protein kinase A (PKA) signaling cascade (Chapter 40). Because the CFTR is activated by cAMP, prostaglandin
E2 (PGE2), serotonin, as well as the cholera toxin and the E. coli heat-stable enterotoxin, all activate chloride secretion. On the other
hand, the loss-of-function mutations of CFTR are the cause of cystic fibrosis, where the chloride transport is impaired or inhibited.
CFTR also has regulatory function: its phosphorylation inhibits the NHE exchanger, thus decreasing Na+ absorption. Interestingly CFTR is
also able to transport chloride in the opposite direction, aiding chloride reabsorption (above).
The basolateral C1− uptake occurs through the Na+ K+ C1− co-transporter (known as NKCC1) and through chloride/bicarbonate
exchangers.
Cystic fibrosis
Salivary amylase and pancreatic amylase digest starch and glycogen in the mouth and
intestine.
How, where and with what enzyme are disaccharides digested? Be specific with what
enzyme breaks down which dissarcharide/linkage.
Chyme is the acidic mixture in the stomach which is neutralized in the intestine by
bicarbonate secreted by the pancreas.
What kind of enzymes are amylases? What are the end products of amylase digestion?
What do amylases not degrade?
Endoglycosidases. They break only alpha 1-4 linkages in the middle of the chain at random
intervals, they never degrade at the end of the chain. Results in a mixture of short,
branched alpha 1-6 and unbranched oligosacchrides with limited dextrins. (dextins,
trisaccharaides, isomatloses, maltose). Amylases do not digest dissarchades into
monosaccharides, alpha 1-6 linkages, or cellulose (B1-4).
How much salivary amylase and pancreatic amylase do we make in one day? How are
they secreted?
1L and 1.5L. Into the mouth and mixed with food during mastication. And into the
duodenum via the pancreatic duct after chyme from stomach has been neutralized by
bicarbonate.
Where are most carbohydrates absorbed? Where do they go after?
BEFORE they enter the large intestine. Mostly in the duodenum and upper jejunum. They
are then transported to the portal system--> to the liver.
What are the main transporters for glucose absorption? Where are they found?
SGLT-1 and SGLT2 in the intestine and kidney. SGLT1 for all of intestinal glucose absorption.
SGLT2 for 90% of renal glucose reabsorption (in proximal convoluted tubule) and SGLT1 for
other 10% (in proximal straight tubule).
What are the main transporters for tranport of glucose into/out of tissue to blood? How do
they work?
GLUT transporters. Facilitated diffusion with gradient/no ATP used. Transport changes
conformation to bind sugar and then release sugar.
1. Primary active transport. Low concentration of Na in the cell maintained by Na/K ATPase
(Need ATP!). 2. Secondary active transport. Na/Glucose Symport (Na with gradient; glucose
against gradient to move glucose into the cell) on the apical side of the epithelium
SGLT2 inhibitors
Flozins (canagliflozin/dapaliflozin), are second-line or third line diabetes treatment (type
2) because they reduce renal tubular glucose reabsorption/ reduce blood glucose without
stimulating insulin release. Also weight loss, reduce bp, and increase high density
lipoproteins.
Glut1=RBC, Brain, fetal tissue; Basal uptake of glucose in tissues to sustain respiration
of cell.
Glut2 = Transports glucose in/out of liver, kidney, and b-pancreatic cells. sends Glucose,
Galactose, Fructose to the portal system to be absorbed by t Glut3.
Glut4= Most abundant in adipose and muscle glucose uptake/out of blood into tissue.
insulin sensitive/increased with insulin present!!! all others are not.
Due to lactase deficiency. Presents with diarrhea, bloating, cramps bc bacteria in large
intestine = H2, CO2, diarrhea. Some subpopulations and older people have it more
commonly. Secondary is because of injury; first to be lost and last to recover.
PROTEIN DIGESTION
Endopeptidases
Absorption of Amino Acids
Transport of Amino Acids into Cells
LIPID DIGESTION
What digestion of triacylglycerides occurs before the intestines? Describe what conducts
this process. Does any absorption occur in this area?
Where does digestion of long chain fatty acids occur? What molecule mediates this?
Pancreatic lipase - what does it do? What are the products? What other components are
required? What drug inhibits pancreatic lipase?
Have a glycerol backbone with 2 FA groups and a phosphate group. Phospholipids are
mainly digested by pancreatic phospholipase A2 (activated by trypsin/bile salts).
PLA2 takes away FA on position 2. PLA2 takes away P1, PLC hydrolyzes bond between
phosphate and glycerol.
PLD breaks bond between phosphate and head group. End result is lysophospholipid and 2
FA.
Add choline to the lysoPL to create lysoPC, absorbed from ileum in micelles
Digestion of cholesterol esters - what enzyme? What is the process and what receptors
are involved?
Free cholesterol is absorbed in the duodenum and jejunum with the aid of NPC1-L1
transporter protein. Cholesterol esters need to be broken down by pancreatic cholesterol
esterase to cholesterol + FA. Ezetimibe inhibits absorption of cholesterol by interfering
with NPC1-L1 receptors.
What makes up the majority of bile? What is the difference between gallbladder bile
and liver bile?
Bile is made in the liver, it mostly water. Organic comounds in bile include lecithin
(phosphatidyl choline), cholesterol, bile salts, and bilirubin). Majority of bile is stored in
gallbladder for times of need, can be recirculated 5-6 times times each day. Gallbladder
bile is a little more concentrated than liver bile, most of the organic components are
concentrated there. Released from gallbladder in response to CCK (produced from lower
duodenum and jejunum)
What is the purpose of bile salts? How do they achieve this? What other roles do they
have? How are they excreted?
Have detergent properties, which help emulsify fats during digestion in intestines to form
mixed micelles (many components). They also keep cholesterol from precipitating in the
gallbladder, activate pancreatic lipase, phospholipase A2, and cholesterol esterase, and are
needed for absorption and transport of fat-soluble vitamins (A, D, E, K). 5% of bile salts are
excreted in faeces, they are the only significant way for cholesterol to be removed from the
body.
Where is free cholesterol absorbed? Where are individual FA absorbed? What about 2-
MAG? Lysophospholipids? How are bile salts reabsorbed?
2-MAG is converted back to a TAG by the readdition of 2 FAs. Fatty acids have CoA
added. Cholesterol is esterified again. All three of these are packaged into chylomicrons,
then sent into lymphatic circulation.
What are some examples of pancreatic insufficiencies? What is cholestasis? What are
some inflammatory bowel diseases? Lipid malabsorption affects what other nutrient
absorption?
Inflammatory bowel diseases include celiac sprue (gluten sensitivity), Crohn disease
(autoimmune), and bowel resections.
Anti-obesity drug that inhibits pancreatic and gastric lipase. Prevents TAGs from being
digested to MAGs, so cannot be absorbed
Olestra
6-8 FA attached to sucrose, it is non-digestible. Wear dark pants, cause you will leave stains
Steatorrhea
http://www.dnatube.com/video/6151/The-Digestive-System
http://slideplayer.com/slide/3383047/
https://www.slideshare.net/enamifat/introduction-to-digestion-and-absorption-local-hormones-of-git-different-digestive-juices
http://www.authorstream.com/Presentation/drraghu74-1526731-control-gastric-secretions/
https://doctorlib.info/anatomy/ross-wilson-anatomy-physiology-health-illness/12.html
https://doctorlib.info/medical/biochemistry/12.html
http://www.tankonyvtar.hu/en/tartalom/tamop425/0010_1A_Book_angol_05_termeleselettan/ch06.html
http://download.nos.org/srsec314newE/PDFBIO.EL13.pdf
http://www.austincc.edu/sziser/Biol%202404/2404LecNotes/2404LNExV/m.Digestive%20System.pdf
https://www.integrativepsychiatry.net/gut_brain_dysfunction.html
http://thepowerofpoop.com/about/about-fecal-transplant/
http://thescienceofeating.com/2017/06/28/gut-flora-holds-key-good-health-heres-keeps-whole-body-healthy/
http://www.uofmhealth.org/news/archive/201611/high-fiber-diet-keeps-gut-microbes-eating-colon%E2%80%99s-lining
http://www.uofmhealth.org/news/archive/201611/high-fiber-diet-keeps-gut-microbes-eating-colon%E2%80%99s-lining
http://www.gutmicrobiotaforhealth.com/en/bacteria-celiac-patients-influence-glutens-digestion-ability-provoke-immune-response/
http://schaechter.asmblog.org/schaechter/2013/06/fine-reading-the-gut-microbiota-of-insects-diversity-in-structure-and-function.html
https://phys.org/news/2016-03-gut-microbiome-remarkably-stable.html