PHYS: Metabolism Flashcards
What is the major site for both absorption and digestion in the GI tract?
small intestine
True or False: almost all digestion and absorption of carbs and protein is completed by the duodenum
FALSE: almost all digestion and absorption of carbs and protein is completed by the MID JEJUNUM
In which division are the vili the longest?
duodenum (where most absorption occurs)
What characteristic of the small intestine epithelium gives the greatest increase in surface area/absorption?
brush border (microvilli)
What are the two types of digestive enzymes?
1) luminal enzymes (secreted in salivary, gastric, and pancreatic juices)
2) Membrane bound enzymes (on apical membrane of intestinal epithelial cells)
What enzymes break down carbs and where are they made?
- Saliva/pancreas: amylase
- Intestinal mucosa: sucrase, maltase, lactase, alpha-dextrinase
What enzymes break down protein and where are they made?
- Stomach: pepsin
- Pancreas: trypsin, chymotrypsin, carboxypeptidase, elastase
- Intestinal mucosa: amino-oligopeptidase, dipeptidase, enterokinase
What enzymes break down lipids and where are they made?
- Saliva: lingual lipase
- Pancreas: lipase colipase, phospholipase A2, cholesterol ester hydrolase
List the endopeptidases.
Pepsin
Trypsin
Chymotrypsin
Elastase
List the exopeptidases.
carboxypeptidase A and B
How do endopeptidases and exopeptidases differ?
Endopeptidases hydrolyze the interior peptide bonds of proteins while exopeptidases hydrolyze 1 AA at a time from the C-terminal ends of proteins and peptides
What are the two major paths of absorption?
Cellular path
Paracellular path
What is the first barrier that must be crossed in the cellular path?
glycocalyx (unstirred water layer that is a barrier to fat-soluble molecules)
What is the paracellular path?
- substances move across the tight junctions between intestinal epithelial cells, through the lateral intercellular spaces, and into the blood.
Which part of the small intestine has the loosest epithelium/tight junctions?
duodenum (and it gets tighter as you move along
True or false: In order to be absorbed, all ingested carbohydrates must be in the form of monosaccharides
TRUE
List the three monosaccharides.
glucose
galactose
fructose
Does any starch metabolism occur in the stomach?
no (salivary amylase is broken down by the acid)
What is the MOA of alpha-amylase (pancreatic)?
Has the ability to cleave interior 1,4-glycosidic bonds of starches (but is unable to cleave beta-linkages of cellulose and other indigestible carbs) into disaccharides
List the disaccharides generated by pancreatic amylase?
alpha-limit dextrins, maltose and maltotriose
True or false: amylase can produce glucose.
FALSE
Where are the enzymes located that break disaccharides down into monosaccharides?
intestinal brush-border enzymes (alpha-dextrinase, maltase, sucrase)
What is trehalose broken down into?
2 glucose
What is lactose broken down into?
glucose + galactose
What is sucrose broken down into?
glucose and fructose
What two types of sugar does sucrase break down?
maltitriose and sucrose
What are the 3 disaccharides found in the diet?
trehalose
lactose
sucrose
True or false: trehalose, lactose and sucrose are NOT acted upon by amylase.
TRUE (they are already disaccharides)
Transport of monosaccharides across the lumen is dependent on what?
the concentration gradient set up by the sodium/postassium ATPase
What are the two apical membrane transporters that bring monosaccharides into intestinal epithelial cells?
SGLT-1
GLUT-5
What does SGLT-1 transport?
transports 1 glucose or galactose with 2 sodium ions into the cell (along the concentration gradient set up by the Na+/K+ ATPase)
What happens to the SGLT-1 transporter after bringing in sugar?
Na+ actively transported out allowing for the release of sugar and the transporter gets recycled back to the apical membrane
What does GLUT-5 do?
allows for facilitated diffusion of fructose along its concentration gradient
What is present on the basolateral membrane to allow monosaccharides to flow down their concentration gradients into the blood?
GLUT-2 transporters
What is released from chief cells in the stomach?
pepsinogen
How does pepsinogen get activated to pepsin?
low pH of stomach
What does pepsinogen do?
breaks down proteins into amino acids and oligopeptides
Where does pepsinogen function?
in the DUODENUM (HCO3- from pancreas)
True or false: pepsin is required for normal protein breakdown.
FALSE (not essential)
True or false: all proteases secreted by the pancreas are in “precursor” form.
TRUE
How does trypsinogen get activated to trypsin?
brush border enzyme enterokinase (initially only a small amount then it autocatalyzes itself)
How do all the other “precursor” proteases get activated?
tryspin activates all the other inactive precursors to their active forms
True or false: pancreatic proteases break down all proteins completely to amino acids.
FALSE: break the protein down into amino acids, dipeptides, tripeptides, and larger peptides (oligopeptides)
True or false: in order to be absorbed, protein must be in the form of free amino acids.
FALSE: must be in the form of free amino acids or di-/tri-peptides
What breaks down oligopeptides into smaller forms for absorption?
brush border peptidases
Which is more efficient, the free AA cotransporter or the dipeptide/ tripeptide cotransporter?
dipeptide/tripeptide cotransporter
What does free AA transport depend on?
cotransported with Na+ so depends on gradient established for Na+/K+ ATPase
True or false: There are different transporters for neutral, acidic, basic and imino amino acids
TRUE
What does dipeptide/tripeptide transport depend on?
cotransported with H+ along H+ gradient created by Na+/H+ exchanger in apical membrane
What happens to dipeptides and tripeptides within small intestine epithelial cells?
most are hydrolyzed by cystoplasmic peptidase within intestinal epithelial cells to amino acid form be transported into the blood (though a very small amount are absorbed into the blood unchanged)
True or false: most instances where an amino acid transporter is absent result in serous sequelae.
FALSE: if you are missing a carrier for amino acids, it is probably not clinically significant (because these can still be absorbed as di- and tripeptides).
Why does cystinuria occur?
lack of cysteine transporter so you cannot reabsorb cysteine from kidney –> stones
True or false: the diet composes a major fraction of the daily fluids that enter the small intestine
false, most is from secretions
List the fat soluble vitamins.
A, D, E, K
How does absorption of fat soluble vitamins differ from water soluble vitamins?
fat soluble uses diffusion, water soluble uses active mechanisms
What is an example of a water soluble vitamin with a very complicated uptake system?
Vitamin B12 (cobalamin)
Where is dietary B12 released?
in the stomach (by pepsin)
What does free vitamin B12 bind to (excreted by salivary juice)?
R proteins
What happens to the R-protein/cobalamin complex?
In the duodenum, pancreatic proteases break down R proteins→ shifting VitB12 over to intrinsic factor (from the gastric parietal cells)
Is IF/VitB sensitive to pancreatic proteases?
NO
Where does the IF/VitB complex get absorbed?
ileum
IF someone is missing intrinsic factor, how do you treat them to prevent pernicious anemia?
get vitamin B12 injections
How does vitamin D stimulate calcium absorption?
promotes calcium absorption from the small intestine by inducing the transcription of calbindin D-28K (transporter) to carry calcium from the lumen to the basolateral membrane
In what forms is iron absorbed from the intestine?
free ferous iron (Fe2+)
heme iron
What is responsible for conversion of ferric iron to ferrous iron for uptake?
gastric acid
What happens if heme iron is taken up by intestinal epithelial cells?
acted upon by lysosomal enzymes within cells to release free iron
What binds to free iron in epithelial cells and transports it to the basolateral membrane?
ferritin
What releases iron into the blood?
ferroportin (when stimulated by hepcidin)
What does iron travel in the blood bound to?
transferrin
What happens when iron in the blood is high?
ferritin is upregulated (store iron) and ferroportin is down-regulated (so no more iron is put into blood)
Are water and electrolytes absorbed more transcellularly or paracellularly?
paracellularly
Because the colon absorbs more water than electrolytes, how does isotonicity remain present?
bacterial breakdown products
What ions are mainly reabsorbed in the colon?
sodium and H+
What do you lose in diarrhea?
K+ and HCO3- (leading to hypokalemia and metabolic acidosis)
List the 4 types of transporters that bring Na+ into epithelial cells.
Na+ apical membrane pores
Na+/solute cotransporter
Na+/K+/2Cl- cotransporter
Na+/H+ exchanger
How do Cl- and water get reabsorbed in the smal intestine?
paracellularly along the electrochemical gradient set up by sodium absorption
How does Cl- get reabsorbed in the terminal ileum and colon?
Bicarbonate/chloride transporters send Cl- in for every HCO3- (made by Carbonic Anhydrase from products of oxidative metabolism) out—explains why stool water is alkaline.
Why is K+ secreted into colonic lumen which Na+ is avidly reabsorbed?
sodium/potassium ATPase on the basolateral membrane
How does aldosterone alter sodium absorption in the colon?
Aldosterone works on colon epithelial cells to increase Na+/K+ ATPases and to place more Na+ channels into the apical membrane
How do sodium and water get secreted by the intestines?
Opening of Cl- channels (CFTR) initiates Cl-Secretion. Sodium and water follow Cl- through paracellular pathways.
Why do apical membrane Cl-channels (CFTR) get activated?
Ach or VIP bind to the basolateral receptor, activate adenylyl cyclase→ cAMP→ opens the Cl- channels (CFTR)
Is metabolic acidosis in diarrhea normal anion gap?
yes (because Cl- is retained)
What type of diarrhea is caused by impaired absorption or the presence of non-absorbable solutes in the lumen of the intestine?
osmotic diarrhea
List 4 reasons for osmotic diarrhea.
- Lack of enzymes (ex. lactase)
- Decreased absorptive surface (ex. celiac disease)
- Precipitation of bile salts (leads to steatorrhea)
- Faster motility (less time for absorption
What type of diarrhea is caused by excessive secretion of fluid by crypt cells?
secretory diarrhea
List 2 causes of secretory diarrhea.
Bacteria
Verner Morrison syndrome
What type of bacteria cause secretory diarrhea?
Vibrio cholera
How does the vibrio cholera toxin work?
Catalyze ADP ribosylation of the alpha-s subunit of the Gs protein that is coupled to adenylyl cyclase. This permanently activates adenylyl cyclase and leads to high cAMP levels and constant opening of the Cl- apical membrane transporter. Cl- flows out, accompanied by Na+ and H2O leading to high volume of diarrhea.
What is Verner Morrison syndrome?
tumor produces VIP allowing for constant activation of adenylyl cyclase and secretory diarrhea
Where are the signals for hunger and satiety integrated?
arcuate nucleus of the hypothelamus
What receives long term signals that stimulate alpha-MSH to stimulate metabolism and inhibit food intake?
POMC
What stimulates POMC?
insulin and leptin
What leads to decreased metabolism and increased food intake and is inhibited by metabolic and satiety signals?
NPY
What inhibits NPY?
leptin
PYY (a bit)
What stimulates NPY?
ghrelin
What works to inhibit the alpha-MSH pathway to promote food intake and decreased metabolism; stimulated by hunger?
AgRP
What inhibits AgRP?
leptin
PYY
What stimulates AgRP?
Ghrelin
When is Ghrelin relased?
released from stomach before you eat to stimulate food intake
How does CKK alter appetite and metabolism?
decreases appetite and decreases metabolism
Where does lipid digestion start?
mouth (lingual lipase) and stomach (gastric lipase)
What do lipases do?
Break down TGs into glyceros and FFAs
Why is it important that the stomach releases chyme slowly into the small intestine?
allows enough time for pancreatic enzymes to digest lipids
What controls gastric emptying?
CCK
How doe lipid digestion products get emulsified to dietary lipid?
bile salts and lysolecithin surround them and produce small droplets of lipid dispersed int he aqueous solution of hte intestinal lumen
What activates procolipase to coplipase?
trypsin
What is the role of colipse?
has a binding site for pancreatic lipase (binds to fat and displaces bile salts to allow the lipase to digest fat)
What is the role of pancreatic lipase?
hydrolyzes TGs into 1 monoglyceride and 2 FAs
What enzyme hydrolyzes cholesterol ester to free cholesterol and fatty acids (and also breaks down monoglyceride into glycerol and FFA)?
cholesterol ester hydrolase
What enzyme is activated by trypsin and hydrolyzes phospholipids to lysolecithin and FAs?
phospholipase A2
What is the exception to the statement that all breakdown products of lipid digestion are hydrophobic and not soluble in water?
glycerol
How do all digestive products (minus sorbitol) become solubilized int he intestinal lumen?
in mixed micelles
What is a micelle?
cylindrically shaped disks with a core of lipid digestive products and an exterior of bile salts (ampipathic)
True or false: micelles enter intestinal epithelial cells.
FALSE: Micelles diffuse to apical membrane of intestinal epithelial cells and lipids are released from the micelle and diffuse down concentration gradient into the cell.
What happens to the products of lipid digestion within the intestinal epithelial cells?
- Bound by FA binding proteins
- Reesterified with FFAs on smooth ER to form original lipids, TGs, cholesterol, ester, and phospholipids
What happens to the re-esterified products?
packaged with apoproteins into chylomicrons
What is a chylomicron?
shell of phospholipids (80%) and apoproteins (20%) with a core of triglycerides and cholesterol
What condition leads to a failure of patients to absorb chylomicrons?
abetalipoproteinemia
Because chylomicrons are too big to enter the blood at capillaries, how do they get into the circulation?
enter lymphatic capillaries (lacteals) by moving between the endothelial cells that line the lacteals. Lymphatic circulation empties these into thoracic duct→ blood.
What would lead to TGs in stool?
- pancreatic insufficiency (not enough lipid digestion due to lack of pancreatic enzymes)
- overly acidified duodenum
What would lead to presence of FAs and monoglycerides in the stool?
- bile salt deficiency (unable to solublize lipid digestion products)
- bacterial overgrowth
- decreased pH
- celiac disease
