Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Gastrointestinal System > Cholesterol and Bile Acid Metabolism - Abali 2/22/16 > Flashcards

Cholesterol and Bile Acid Metabolism - Abali 2/22/16 Flashcards

1
Q

composition of hepatic and gallbladder bile

A

bile acid

phospholipid

cholesterol

bilirubin (0.3%)

protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

summary of bile action in digestive system

A
  • synthesized from cholesterol in liver

when you have a fatty meal, CCK released by endocrine cells

  • contracts gallbladder
  • opens sphincter of Oddi, releasing bile into duodenum

bile is a detergent (it can solubilize fats/oils) → bile acids/salts form micelles with ingested lipids

  • micelles are digested by lipases and/or made into chylomicrons

bile salts absorbed in ileum, move back to liver via hepatic portal vein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

properties of bile acids and salts

why is this important?

A
  • planar
  • amphipathic (hydrophilic/phobic)
    • philic: all COOH and OH groups on one side

allows lipids to packaged in a way that lets them be transported in blood and sequesters them for lipase to go to work

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

cholesterol and role of liver in processing

A
  • chol is NOT required in diet (bc we can make it through de novo synth)
  • sources: dietary and de novo synthesis (mostly liver but also extrahepatic tissues)
  • liver is major regulator of chol metabolism
    • exports it in VLDL
    • coverts it into bile acids/salts
    • excretes it in bile

**cholesterol can only be excreted via bile acids/salts and bile in feces

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

cholesterol excretion

A

can’t degrade it to water and CO2 (no way to break it down to component parts)

  • either make it into other stuff (vitamin D, steroid hormones) or eliminated in feces as…
    • unmodified chol
    • bile acids
    • reduced chol (5% thats not picked back up into portal circ reduced via bacteria into cholestanol, coprostanol)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

primary and secondary bile acids

A

liver takes cholesterol, hydroxylates it to make primary bile acids (later modified via conjugation), which are then deconjugated/dehydroxylated by intestinal bacteria to become secondary bile acids

  1. cholic acid → deoxycholic acid
  2. chenodeoxycholic acid → lithocholic acid
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

committed step in bile acid synthesis [enzyme]

A

7-alpha hydroxylase

cytochrome P450 enzyme

  • *CYP7A**
  • shortens a side chain/adds a COO, reduces a double bond, adds OH at 7 and 12 positions to make…*

cholesterol → cholic acid

regulation via

  • substrate activation: cholesterol activates
  • product inhibition: cholic acid inhibits
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

CYP 7A

A

cytochrome P450 enzyme: 7alpha hydroxylase

regulates committed step in bile acid synthesis

shortens a side chain/adds a COO, reduces a double bond, adds OH at 7 and 12 positions to make…

cholesterol → cholic acid

regulation via

  • substrate activation: cholesterol activates
  • product inhibition: cholic acid inhibits
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

difference between cholic acid and chenodeoxycholic acid

A

both primary bile acids (CYP7A key in synth)

cholic acid: 3 OH groups (3, 7, 12 positions)

chenodeoxycholic acid: 2 OH groups (3, 7 positions)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

synthesis of bile acids from cholesterol

A

catalyzed by CYP 7A

  • OH groups added
  • side chain shortened, COO group added
  • double bond reduced

chenodeoxycholic acid lacks the C12 OH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

primary bile acids are modified through conjugation

  • define
  • why?
A

bile acids are emulsifiers, so we want them to be more charged so as to be better detergents

  • → cholyl CoA (pKa 6)
  • conjugation with glycine or taurine (made from Cys) lowers the pKa of bile acids
    • taurocholic acid/taurochenodeoxycholic acid (pKa 2)
    • glycocholic acid/glycochenodeoxycholic acid (pKa 4)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

conversion of primary bile acids (conjugated) to secondary bile acids

A

bacterial transformation (in intestine)

  • deconjugation → cholic/chenodeoxycholic acid
  • dehydroxylation at C7 → deoxycholic/lithocholic acid

makes them more insoluble

  • some absorbed through hydrophobic cell membranes
  • most released in feces
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

biliary bile acids [

vs

fecal bile acids

A

biliary bile acids leaving liver are virtually all conjugated

fecal bile acids are virtually all unconjugated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

bile acids vs bile salts

A

interchangeable terms - depends on whether they still have their proton (acids) or not (salts)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

conjugated bile acids

A
  1. glycocholic acid
  2. glycochenodeoxycholic acid
  3. taurocholic acid
  4. taurochenodeoxycholic acid

predominate in biliary bile acids (in bile duct)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

unconjugated bile acids

A
  1. cholic acid
  2. chenodeoxycholic acid
  3. deoxycholic acid
  4. lithocholic acid

predominate in fecal bile acids (in intestine)

17
Q

enterohepatic circulation

  • percentages
  • link to chol
A
  • approx 95% of conjugated bile acids: reabsorbed in distal ileum, returned to liver via portal vein (enterohepatic circulation)
  • remaining 5%: move into → secondary bile acids
    • eventually lost in feces
    • since bile acids/salts originate from cholesterol, this is the way the body excretes cholesterol

0.5 g excreted daily (out of approx 15-30 g secreted)

18
Q

BAS

  • definition
  • mech of action
  • application, ex
A

bile acid sequestrant/resin

  • bind to bile acids, prevent them from being reabsorbed in intestine
    • forces liver to up the synth of bile acids (i.e. use up stores of chol, take up more chol from plasma)

application

liver upregulates LDL receptor, effectively decreases LDL in circulation!

  • cholestyramine (Questran)
  • colesevelam (Welchol)
  • colestipol (Colestid)
19
Q

major bile acid transporters in enterohepatic circulation

A

hepatocyte to bile canaliculus:

BSEP (bile acid export pump) - ATP dependent

  • bile does its thing from duodenum on into ileum

from int lumen into/through distal ileal cell into portal circ:

ASBT (apical Na-dep bile acid transporter) - Na dep

OSTalpha-OSTbeta (basolateral organic solute and steroid transporter)

  • 95% of bile absorbed in distal ileum moves through portal vein and up into liver sinusoids

from sinusoids into hepatocytes:

NTCP (Na-dep taurocholate cotransporting polypeptide) - Na dep

OATP (organic anion transporting polypeptides)

  • 5% of bile that moves into colon either taken up (v small fraction) or excreted in feces
20
Q

cholelithiasis

A

formation of gallstones (more yellowish) via crystallization of cholesterol in bile

  • happens when you have extra chol secretion into biliary tract

caused by…

  • severe ileal disease: reduced enterohepatic circ: increased fraction of chol in bile (bc CYP7A can’t keep up with demand)
  • bile duct obstruction
  • severe hepatic dysfunction: messes with liver enzymes
  • genetic susceptibility (LITH genes)
21
Q

conditions in which gallstones favored

A

proportions of phosphatidylcholine/lecithin (phospholipid), bile salts, and chol determines the solubility of chol in bile

more gallstones if you:

reduce PL

reduce bile

increase chol

22
Q

formation of gallstones in biliary tree

  • locations
    • assoc symptoms
A

1. in cystic bile duct

  • painful gallbladder contractions

2. blocking common bile duct

  • no bile release into duodenum
    • failure to digest fats → steatorrhea, diarrhea
    • gray feces (no bile pigments)
  • failure to excrete bilirubin → jaundice

​3. blocking duodenal papilla

  • no bile/pancreatic secretion release into duodenum
    • serious malnutrition (can’t digest chyme)
  • acute pancreatitis
23
Q

morphological features of cholestasis

A

everything gets BIG for diff reasons

  • cholestatic hepatocytes are enlarged
  • bile canaliculus enlarged
  • Kupffer cells (macrophages in hepatocytes) engulf excess bile - seen with bile pigments
  • cell apoptosis

excess bile blocks stuff up

  • bile plugs in bile ducts
24
Q

steatorrhea

A

fat in feces due to malabsorption in intestines

25
Q

Zollinger Ellison syndrome

A

gastrin-secreting tumor or hyperplasia of the islet cells in the pancreas causing overproduction of gastric acid, resulting in recurrent peptic ulcers

26
Q

dumping syndrome

A

weakness, abdominal discomfort, and sometimes abnormally rapid bowel evacuation, occurring after meals in some patients who have undergone gastric surgery

27
Q
A

Gastrointestinal System (35 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions