Digestion

Fox Chapter 18, figures from chapters 4, 6 & 19

Chemistry

TRANSPARENCY (From intro bio)
Fig. 18.1
break down long chain proteins, polysaccharides and nucleic acids into monomers
recall hydrolysis (opposite of dehydration synthesis) (hydro-water lysis-break apart)
if not broken down, proteins which are non-self would make a big antigen invasion

TRANSPARENCY (From intro book)
Tube - Alimentary canal

Input - output

Fig. 18.2
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

Overall anatomy

(from mouth to stomach)

Mouth - teeth, lubrication, salivary amylase to disaccharide maltose - starch tastes sweet (only starch in mouth)
-ase enzymes
Pharynx swallowing
Esophagus - bolus, peristalsis
Cardiac oriface

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

Fig. 18.5
Stomach - gastric mucosa - mucus protect

Fig. 18.6
from parietal cell: HCl kill bacteria
stop amylase
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

Fig. 4.4
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

Intestine:

enzymes - lactase, maltase, sucrase, others
mitosis - since cells digest themselves
absorption - food and water

Fig. 18.10
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

Fig. 18.12
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)

Fig. 18.33
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 lumen.

Fig. 6.21
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

Fig. 18.27b
Pancreas is responsible for dumping in many of the enzymes
Unit of this exocrine gland is the acinus
Zymogen refers to precursor of enzyme.

Table 18.4
"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 hormones.
Pancreas puts out bicarbonate (alkaline) to neutralize stomach acid.
Optimum pH for for trypsin is 8.

Fig. 18.25
Pancreas and common bile duct (from liver and gall bladder) dumping into duodenum.
When I took organic chemistry lab (1966-7) we used gall stones for a cholesterol extraction.
Note: Islets of Langerhans (endocrine tissue) in pancreas where alpha cells make glucagon and beta cells make insulin.

Liver

Very few enzymes.
Emulsify fats.
Iron recycling.
Eliminate some wastes to feces.
Detoxify.

Detoxification

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.

Fig. 18.22
Fig. 18.23
Erythrocyte iron recycling, bile pigment (bilirubin) ->urobilinogen turns feces dark.
Also colors urine.
Hepatitis (disorder which spills bile into blood) - turns skin yellow (jaundice) (feces are not as dark, urine is darker)

Fat digestion

Fig. 18.24
bile salts, salts of cholesterol, that emulsify fats

Fig. 18.35
Liver contributes to fat digestion

Fig. 18.34
Triglycerides are broken to monoglycerides and free fatty acids.

Fig. 18.36
Despite this breakdown, fats are reassembled, put in droplets with proteins and carried in lymph duct called lacteal.

Hormones

Table 18.5
Local hormones control digestion - Many found later in other places

Fig. 18.30
from stomach:
food stimulates gastrin which, in turn, stimulates gastric juice until there is a low (acidic) pH
from duodenum:
Cholecystokinin (CCK) - liver and pancreas
Secretin for bicarbonate release
Enterogastrones to slow gastric emptying

Appetite

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 sex drive.
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 Parkinson's disease.

Fig. 19.3
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.

Recent literature

Leptin

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, 110-115.

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 transcript (CART)
leptin regulates synaptic plasticity and axon guidance

Exam questions from 2004 - 2008 related to this outline

Loss of what hormone would cause an adrenalectomized animal to crave salt?

aldosterone

What is the function of the "microsomal fraction" in liver cells?

detoxify

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 scarring disorder?

cirrhosis

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?

leptin

The opposite of dehydration synthesis (condensation reaction) happens in digestion. What is this called?

hydrolysis

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?

pancreas

Cholera toxin affects the level of what famous "second messenger" in the intestinal epithelium?

cAMP

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?

liver

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?

emulsify fats

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
turn].

glucose/sodium cotransporter

Cholera toxin interferes with water transport in the intestines in a mechanism utilizing what famous "second messenger?"

cAMP

What is the name of the lymph vessel in the intestinal villus that is important if absorption of fat?

lacteal

Many factors including hormones control gastric emptying via what "valve?"

pyloric sphincter

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 for this?

amylase

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?

chyme

What do you call the inclusions in pancreatic acinar cells with reference to the fact that they contain precursors of enzymes?

zymogen granules

What is the name biochemists use for the smooth endoplasmic reticulum of liver cells responsible for detoxifying toxins?

microsomal fraction

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?

basolateral

In a healthy person, what is the fate of bilirubin after it arrives at the liver?

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 body)?

triglycerides combined with protein in droplet called chylomicron

Name an enzyme derived from a pancreatic precursor that is an endopeptidase.

trypsin, chymotrypsin

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." Translate.

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 in cell

As heme is broken down, one of the products is bilirubin. What becomes of this substance?

conjugated to gluconuride, converted to uropilinogen, put out in feces and urine

The hepatic portal vein carries blood from the small intestine to where?

liver

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.

HCl, pepsinogen

What would be the cause of death if you had cholera, and how might you prevent death if you were nowhere near medical help?

dehydration, gatorade

What specialization in the stomach regulates gastric emptying into the small intestine?

pyloric sphincter

"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?

lack leptin

What is the word for the coordinated wave of smooth muscle contraction that propels a bolus of food forward through the esophagus?

peristalsis

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?

cholera

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?

pepsinogen

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 cells." Elabortate.

parietal cell puts out acid which converts chief cell's pepsinogen into pepsin

Why do some people occasionally drink a spoonful of baking soda mixed in water?

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?

Brush border

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


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