Fox Chapter 18, figures from chapters 4, 6 & 19
(From intro bio)
break down long chain proteins, polysaccharides and nucleic acids into monomers
recall hydrolysis (opposite of dehydration synthesis) (hydro-water lysis-break
if not broken down, proteins which are non-self would make a big antigen
(From intro book)
Tube - Alimentary canal
Input - output
One emphasis will be on how the human digestive system invests many juices
(hydrolases = enzymes which catalyse hydrolysis)
Some glands have ducts and these are called exocrine glands.
This is in contrast with endocrine glands (ductless, for hormones, which
are also involved in digestion)
800 g food IN per day
1200 ml water
/ 7000 ml GLANDS
50 g solid OUT
100 g water
(from mouth to stomach)
Mouth - teeth, lubrication, salivary amylase to disaccharide maltose - starch
tastes sweet (only starch in mouth)
Esophagus - bolus, peristalsis
An integrative story
Rats cannot vomit (cardiac oriface cannot open for reverse peristalsis).
They are very good at learning, in one trial, to permanently avoid tastes
which make them sick. (You too may have developed a temporary dislike of
foods you ate before getting sick.) They can only be poisoned by chemicals
with a delayed reaction like Warfarin (warf = Wisconsin alumni research
foundation) which is an anticoagulant. (It is also used in lower doses to
prevent heart attack (coronary thrombosis).
Stomach - gastric mucosa - mucus protect
from parietal cell: HCl kill bacteria
From chief cell: pepsinogen ---(HCl, pepsin))--> pepsin (proteolytic)
optimum pH for pepsin is 2
(Inactive forms called zymogens)
Heartburn, antacids, ulcer (although it is now known that a specific bacterium,
Helicobacter pylori, is associated with ulcer)
very little absorption in stomach - exceptions: aspirin, alcohol
The optimum pH for pepsin (proteolytic enzyme in stomach) is acidic while
for trypsin (proteolytic enzyme in intestine) is slightly basic. And for
salivary amylase, it is neutral.
Fig. 18.5 again
Pyloric sphincter regulates emptying of acidic gastric juice to duodenum.
In duodenum, bile from liver and bicarbonate and enzymes from pancreas add
to enzymes from small intestine
enzymes - lactase, maltase, sucrase, others
mitosis - since cells digest themselves
absorption - food and water
Villi (big) increase surface area. Note mitoses in crypts.
Here is a micrograph
from our histology course dramatizing the tremendous increase in apical
surface area of intestinal cells caused by the microvillar brush border.
Signalling by G-protein involving cAMP (covered earlier) is disrupted by
cholera toxin - a life-threatening diarrhea, must replace fluids - salts
and glucose (as in the electrolyte coctails athletes drink like Gatorade)
facilitate water absorption
The microvilli in the intestines have a special name, the brush border.
Protease (enteropeptidase turns trypsinogen into trypsin which, in turn,
makes chymotrypsin and carboxypeptidase (and others)
How proteins are broken down and absorbed is complex.
Trypsin and chymotrypsin are endopeptidases.
Carboxypeptidase, exopeptidase, cuts carboxy terminal.
Aminopeptidase (shown on brush border) cuts amino terminal.
Di- and tri-peptidases are intracellular.
Intestinal cells digest themselves, and their enzymes go into intestinal
how glucose gets absorbed
same story as for kidney, and, in fact, notice "lumen of kidney tubule
or small intestine"
apical, cotransport with sodium
basolateral Na+-K+ATPase plus glucose facilitated transport
Pancreas is responsible for dumping in many of the enzymes
Unit of this exocrine gland is the acinus
Zymogen refers to precursor of enzyme.
"pro..." as in "procarboxypeptidase and "...ogen"
as in "chymotrypsinogen" --a peptide fragment is cut off from
a larger precursor protein to make active enzyme; there are many examples
like this in biology, for instance prohormones cleaved to make active peptide
Pancreas puts out bicarbonate (alkaline) to neutralize stomach acid.
Optimum pH for for trypsin is 8.
Pancreas and common bile duct (from liver and gall bladder) dumping into
When I took organic chemistry lab (1966-7) we used gall stones for a cholesterol
Note: Islets of Langerhans (endocrine tissue) in pancreas where alpha cells
make glucagon and beta cells make insulin.
Very few enzymes.
Eliminate some wastes to feces.
Portal blood veins (circulatory system "wired" in series is unusual,
another famous example being the hypothalamus of the brain which feeds to
the pituitary gland and kidney cortex to medulla). Via hepatic portal vein
pick-up from small intestine is first delivered to liver cels. There, "microsomal
fraction" (how biochemists view the smooth endoplasmic reticulum) has
enzymes to detoxify. Enzymes like those that detoxify drugs like barbiturates
are increased on exposure to toxins (inducible). Alcohol -(alcohol dehydrogenase
(ADH) )-> aldehyde - (aldehyde dehydrogenase)-> acetic acid. With
AcetylCoA, acetic acid can add to fatty acid chains 2 carbons at a time.
There is a fatty metamorphosis of the liver from one binge. Continued heavy
drinking leads to scarring and cirrhosis.
Erythrocyte iron recycling, bile pigment (bilirubin) ->urobilinogen turns
Also colors urine.
Hepatitis (disorder which spills bile into blood) - turns skin yellow (jaundice)
(feces are not as dark, urine is darker)
bile salts, salts of cholesterol, that emulsify fats
Liver contributes to fat digestion
Triglycerides are broken to monoglycerides and free fatty acids.
Despite this breakdown, fats are reassembled, put in droplets with proteins
and carried in lymph duct called lacteal.
Local hormones control digestion - Many found later in other places
food stimulates gastrin which, in turn, stimulates gastric juice until there
is a low (acidic) pH
Cholecystokinin (CCK) - liver and pancreas
Secretin for bicarbonate release
Enterogastrones to slow gastric emptying
It is worth mentioning that hunger and satiety are complex
In old work on brain lesions, LH (lateral hypothalamus) was called the hunger
center, while the VMH (ventromedial hypothalamus) was considered to be the
satiety center, but it never turned out to be so simple.
Hypothalamus is important in many motivated behaviors including thirst and
Affect (the aspect of perception of goodness or badness of a stimulus) is
linked through the nigrostriatal tract (bundle of nerve axons) which uses
the neurotransmitter dopamine and which is deficient in patients who have
Now it appears that there is a hormone which is called leptin which is released
by (well-fed) fat cells which causes the brain to decrease apetite.
Specific appetite for salt after adrenalectomy eliminates aldosterone.
JKElmquist & JSFlier, The fat-brain axis enters a new dimension Science
304, 63-64, 2004 (Perspectives)
SGBouret, SJDraper & RBSimerly, Trophic action of Leptin on hypothalamic
neurons that regulate feeding, Sci 304, 2004, 108-110
SPinto, AGRoseberry, HLiu, SDiano, MShanabrough, XCai, JMFriedman, TLHorvath,
Rapid rewiring of arcuate nucleus feeding circuits by leptin, Sci 304, 2004,
ob/ob mice are leptin deficient
arcuate nucleus of hypothalamus
orexigenic, Neuropeptide Y (NPY) and agouti-related protein (AgRP)
anorexigenic, proopiomelanocortin (POMC) and cocaine- and amphetamine-regulated
leptin regulates synaptic plasticity and axon guidance
Exam questions from 2004 - 2011 related to this outline
Say something about backward movement or reverse peristalsis at the
vomiting, rats cannot do it so they do not return to tastes that made them
What is the cause of stomach ulcer?
acid, bacterium Helicobacter pylori
What is the use of bicarbonate secretion from the pancreas?
neutralize acidy coming from stomach
"Salt and glucose facilitate the absorption of water across the intestinal
epithelium." Under what circumstances would this knowledge allow you
to save somebody's life?
give someone with Cholera Gatorade before EMS personnel come to hook up
In a healthy person, urobilinogen is eliminated via the urine and (how else?).
in the feces
Facilitated by bile salts and catalyzed by lipase, triglyceride plus two
water molecules is converted into (what three molecules?) in the intestinal
a monoglyceride plus two fatty acids
Obese mutant mice are deficient in leptin. Answer either (1) where (in a
normal animal) leptin is made or (2) what part of the brain it affects.
adipose tissue, arcuate nucleus of hypothalamus
Why would it be useful for chief cells to have pepsinogen rather than pepsin
in their secretory vesicles?
so it does not break down proteins until it is in the stomach
Proteins are broken into amino acids, and these are what move across the
basolateral border of the intestinal epithelium. How does this differ for
the apical surface?
di- and tri-peptides also move across the brush border
Why would a barbiturate have a stronger effect on a person who had not been
taking barbiturates than on a person who had been taking barbiturates?
detoxifying enzymes in smooth ER (microsomal fraction) of liver cells are
What, if any, type of polymer would be broken into monomers if given enough
time in the presence of salivary amylase?
Chief cells: answer EITHER (1) What is the name of the zymogen (precursor)
in the granules of these cells. (2) Acid secreted (from what cell?) helps
to form the active enzyme from the precursor?
A SEVERE stomach disorder was once attributed to excess stomach acid. A
further elucidation of this disorder was worthy of the 2005 Nobel prize
in medicine (awarded to Marshall and Warren). Answer either (1) What disorder?
Or (2) What was the cause of the disorder they discovered?
ulcer, bacterium (Helicobacter pylori)
Enzyme activity as a function of pH: describe the graphs for pepsin vs.
peaks are at 2 and 7 respectively
Say something about how or where trypsin is activated.
trypsin is activated in the intestinal lumen by chopping a fragment from
the zymogen under the influence of enderokinase on the brush border (or
by trypsin that has already been activated)
In reference to lipase in the intestinal lumen, tell me either (1) What
is the source of lipase? Or (2) What are the products when it acts on a
pancreas, monoglyceride plus two fatty acids
Why is the function of the hepatic portal vein so important?
It delivers materials absorbed from the intestines to the liver for detoxification
Amino acids stimulate G cells to release gastrin. State one of the secretions
that result from this.
One cell (ECL cell) puts out histamine causing parietal cell to put out
Using the correct terminology about the drug's affect on appetite (hunger),
tell me about amphetamine.
it is anorexogenic (it causes anorexia)
WARFarin: Answer EITHER (1) Why is a substance like this effective for poisoning
rats when, otherwise, it is difficult to poison a rat? Or (2) Why might
it be given, in lower than poisonous doses, to a person?
They will avoid the taste of something that makes them sick but the delayed
anticoagulant action is not noticed (until it is too late), anticoagulants
decrease the chance of a thrombus or an embolism
Absorption of what important substance from the gut is disrupted by cholera
Why is it useful to have a lot of mitosis in the crypts of intestinal villi?
Intestinal cells digest themselves and need to be replaced
"In digestion, we break proteins down into amino acids for absorption."
How would you modify that statement for the apical membrane of intestinal
Dipeptides and tripeptides also cross this membrane
Why is the function of the microsomal fraction of hepatocytes so important?
Detoxify drugs, alcohol, etc
Loss of what hormone would cause an adrenalectomized animal to crave salt?
What is the function of the "microsomal fraction" in liver cells?
Mitosis in the crypt of the villus is needed because of a short life expectancy
of which cells?
intestinal epithelial cells
Repeated fatty metamorphosis of liver from alcohol binges leads to what
In addition to facilitated diffusion at the basolateral cell surface, what
is necessary for glucose transport in kidney tubule and intestinal cell?
(Include process and location.)
apical cotransport with Na+
What hormone from adipose tissue contributes to weight regulation?
The opposite of dehydration synthesis (condensation reaction) happens in
digestion. What is this called?
What is the optimum pH for pepsin?
very acidic (2)
Recycling of what kind of cell contributes to the dark color of feces, the
yellow color of urine and the yellow skin in jaundice?
red blood cells
What is a zymogen?
inactive forms of digestive enzymes
Where does trypsinogen come from?
Cholera toxin affects the level of what famous "second messenger"
in the intestinal epithelium?
The portal vessel in the digestive system connects the intestine (where
absorption takes place) to that organ?
liver (its the hepatic portal vessel)
Jaundice is a symptom of a disorder of what organ?
What is the function of cholecystokinin (CCK)?
hormone in digestion, slows gastric emptying, cranks up pancreatic secretions
What is the function of salts of cholesterol made by the liver and secreted
into the small intestine?
In the intestine and the kidney tubule, three processes are needed for glucose
transport, (1) basolateral sodium pump, (2) basolateral facilitated diffusion,
and (3) apical... [your
Cholera toxin interferes with water transport in the intestines in a mechanism
utilizing what famous "second messenger?"
What is the name of the lymph vessel in the intestinal villus that is important
if absorption of fat?
Many factors including hormones control gastric emptying via what "valve?"
When I was in first grade, we were told to keep a saltine cracker in our
mouth and notice that eventually it tasted sweet. What enzyme is responsible
You swallow a bolus, and it gets broken apart and mixed with lots of fluid.
What is the name of the fluid mixture emptying into the intestine?
What do you call the inclusions in pancreatic acinar cells with reference
to the fact that they contain precursors of enzymes?
What is the name biochemists use for the smooth endoplasmic reticulum of
liver cells responsible for detoxifying toxins?
Where are the dipeptidases and tripeptidases responsible for the final breakdown
of proteins to amino acids in digestion?
inside the intestinal cell
If one glucose transporter is on the brush border, where (specific cell
surface) is the other?
In a healthy person, what is the fate of bilirubin after it arrives at the
converted and out in feces
What is the source of the digestive enzyme that converts fats to fatty acids
plus a monoglyceride?
lipase is from pancreas
What does it mean to say a substance is orexigenic?
makes you want to eat
Where is the median eminence?
Where hypothalamus connects to pituitary
Argue that the effect of a hypothalamic lesion on weight regulation might
result from loss of affect by interrupting the nigrostriatal tract. Be specific
about what effect you are talking about and/or what part of the hypothalamus.
weight loss from lateral hypothalamus lesion might be from not appreciatng
the "goodness" of food
List one (of the several) effect of gastrin.
make parietal cell secrete HCl or chief cell secrete pepsinogen (or ECL
cell secrete histamine)
Why is a portion of the hypothalamus referred to as "supraoptic?"
it is above optic chiasm
In what molecular form is fat absorbed from the intestinal cell (to the
triglycerides combined with protein in droplet called chylomicron
Name an enzyme derived from a pancreatic precursor that is an endopeptidase.
What are zymogen granules in pancreatic acinar cells?
contain precursors of digestive enzymes like trypsinogen
"Enterokinase on the brush border cleaves trypsinogen to activate trypsin."
the microvilli on intestinal epithelial cells activate the proteolytic enzyme
by cutting off a peptide fragment
What is the purpose of bicarbonate secretion by the pancreas?
neutralize stomach acid for intestine
"Proteins are hydrolyzed into singal amino acids to be absorbed by
intestinal epithelial cells and passed into the blood stream." Why
is this not the whole truth?
peptides of 2 and 3 aminoacids can be taken into cell for final breakdown
As heme is broken down, one of the products is bilirubin. What becomes of
conjugated to gluconuride, converted to uropilinogen, put out in feces and
The hepatic portal vein carries blood from the small intestine to where?
What happens to a monoglyceride inside a cell of the small intestine?
two fatty acids added (converted to fat (triglyceride)
Gastrin stimulates secretions of parietal and chief cells. Name these secrtetions.
What would be the cause of death if you had cholera, and how might you prevent
death if you were nowhere near medical help?
What specialization in the stomach regulates gastric emptying into the small
"Leptin causes a decrease of the orexigenic neuropeptide Y from the
arcuate nucleus." Translate.
neuropeptide Y from that part of the hypothalamus would cause the opposite
of anorexia, so the protein leptin should be good for weight loss
Go on a drinking binge and there will be fat in the liver the next day.
Biochemically, how did that fat get there?
alcohol -> aldehyde -> acetic acid (adds 2 carbons to a fatty acid)
The same sort of drug given to heart patients to decrease the likeliness
of a thrombus is very useful as a rat or mouse poison. Why?
rats avoid tastes of foods that made them sick and anticoagulants work so
slowly that they never make the association
Bilirubin results from what ativity in what organ?
derived from red blood cell hemoglobin, handled by liver
What molecules make up the chylomicrons that are transported to the lacteal?
triglycerides plus proteins
Why are ob/ob mice obese?
What is the word for the coordinated wave of smooth muscle contraction that
propels a bolus of food forward through the esophagus?
Baking soda would be a quick fix for what digestive ailment?
"heartburn" caused by excessive stomach acid
The appropriate signalling that involves cAMP for water absorption in the
intestine is disrupted by what toxin?
After enzymes act on proteins in the intestinal lumen, list every product
of that degradation that gets absorbed into the intestinal cell.
single amino acids, dipeptides, tripeptides
Conversion to what molecule explains why alcohol consumption can cause fat
deposits in the liver?
acetic acid (acetyl coA)
"Gastrin stimulates parietal cells to secrete HCl." In parallel,
it stimulates chief cells to secrete what?
Why might the nigrostriatal dopamine tract have to do with hunger/satiety?
contributes to motivation and affect
What indication of body energy stores would cause leptin to increase?
increased fat in adipose tissue
"Agouti-related protein (AgRP) is orexigenic." Translate.
this protein, oddly related to coat color, increases desire to eat
"The product of the parietal cells activates the product of the chief
parietal cell puts out acid which converts chief cell's pepsinogen into
Why do some people occasionally drink a spoonful of baking soda mixed in
baking soda = "bicarbonate of soda" = sodium bicarbonate, neutralizes
stomach acid, helps with "heart" burn
Away from emergency responders, what can you offer better than water to
rehydrate a cholera victim?
an electrolyte-glucose coctail such as Gatorade is absorbed better
The microvilli on the surface of the intestinal cells are so famous that
they have a name. What is that name?
Why, in terms of chemistry or process involved, does hepatitis lead to jaundice?
inflammation has hepatocytes spill bilirubin (from hemoglobin recycling)
into blood instead of feces
In terms of fat digestion, what is transported across the basolateral surface
of the intestinal epithelium into the lacteal?
chylomicrons are triglycerides bound to proteins
You were shown that amino acids stimulated the G cell to release gastrin
which caused the production of (what?) (also where?).
(via an intermediate ECL cell that releases histamine): acid in the stomach
"Agouti-related peptide (AgRP) is orexigenic." Explain to someone
who is not as sophisticated as you (are supposed to be) either: The meaning
of orexigenic. Or. How (in the heck) did we get on the topic of agouti?
opposite of anorexigenic, stimulating appetite. Although agouti has to do
with coat color, this protein which is orexigenic is like agouti, hence
that seemingly esoteric naming
For glucose absorption from the gut, what is the process on the basolateral
surface that requires energy?
The sodium pump
Sometimes endopeptidases will cut off fragments that are two amino acids
long. What becomes of these?
"In histology, you see zymogens located in acinar cells." What
does that have to do with digestion?
These granules house the precursors of digestive enzymes of the pancreas
Relate the hepatic portal vessel with the "microsomal fraction"
(smooth endoplasmic reticulum of the hepatocyte).
This gives the liver a chance to detoxify what is absorbed from the gut
before it gets to the systemic circulation
"A lesion in the lateral hypothalamus (LH) gives you a thin rat, hence
the LH is a hunger center." What have we learned since this conclusion
was first reached that gives us a different view of the role of the LH?
The LH has the dopamine tract that is useful in motivation (affect) in general
Make an argument that salivary amylase is not of significant value in the
overall hydrolysis of macromolecules for digestion.
swallow soon and inactivated in stomach
At what structure is gastric emptying controlled.
"Proteins are broken down into amino acids and that is what is absorbed."
Why is this not the whole truth regarding the apical surface of the intestinal
uptake of di and tri peptides
Why is jaundice one sign of hepatitis?
b/c bile pigments build up in blood
"Everybody knows about (what structure that feeds blood from the small
intestine to the liver?) if they took a course like this."
hepatic portal vein
What are the products when lipase acts on triglyceride in the lumen of the
2 fatty acids and monoacyl glycerol
With the G cell, the ECL cell, histamine, amino acids, and the vagus nerve,
answer either (1) What hormonal system?, (2) That hormone affects what cell
type? Or (3) That cell type releases what?
gastrin, parietal, HCl
Homozygous obese (ob/ob) ­p; Answer either (1) What is the protein
product of that gene that is missing? Or (2) What tissue releases this product
(in non-mutant mice)?
Why would it be useful to have the proteolytic enzymes in digestion stored
as inactive precursors in the granules (zymogens) in the cells that secrete
so enzymes do not digest their granules and cells
Why are enzymes on the brush border important for trypsin function?
they convert trypsinogen to trypsin
Heme is broken down to iron, carbon monoxide and (fill in the blank). (OK
if you say the immediate product or subsequent steps in the processing of
biliverdin, bilirubin, bilirubin glucuronide (conjugated bilirubin)
To bring fats into the lacteal, what, in fact, is transported across the
basolateral membrane of the intestinal epithelium cell?
chylomicrons (tryglycerides and proteins)
Why was it relevant to remind you about Parkinson's disease after saying
that lesions of the lateral hypothalamus caused the rat to lose weight?
lesions would interrupt nigrostriatal dopamine tract causing loss of affect
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