Bile Metabolism Flashcards
(45 cards)
What is bile?
It’s an aqueous solution of bile acids and bile salts (BA ans BS = majority), phospholipids, cholesterol, and bilibubin. Made from liver.
What are the jobs of bile
- Lipid digestion and absorption, including fat soluble vitamins (ADEK)
- It’s a means fro excretion of cholesterol and bilirubin.
Where is bile made? What happens to it after it is made What causes bile to be released after storage in the gallbladder?
BA and BS are both made in hepatocytes from cholesterol in the liver. It then enters the common bile duct where it can go straight to second part of duodenum of turn into the gallbladder. it is normally stored during fasting and released when you eat through the stimulation of CCK, whcih contracts the gallbladder, pushing bile into the common bile duct.
What is the job of CCK?
Upon Fatty acid presence, it causes gallbladder to contract (increasing flow of bile into common bile duct and causes sphincter of oddi to relax (increasing flow of bile into duodenum.).
What is the main precursor of BA and BS?
Cholesterol (FOUR (4) linked ring structures…last of which is a pent, not a hex…with a tail and an OH at the other end.). Very hydrophobic, except for at the area near the OH.
What two products are made from cholesterol (C27, OH is only at 3 position)? AKA what are the primary bile acids?
The primary bile acids are:
1. Cholic acid (C24, OH at 7 and 12)
2. Chenocholic acid (C24, OH at 7)
Both these guys have more OH added to them, in addition to 1 COOH added to each one. These guys are thus more hydrophilic, and can dissolve better in water
What is significant about the location of the polar parts (COOH, OH) of the cholic and chenocholic acid?
The polar parts are all on one side of the molecule, so there is a designated polar and non-polar side. That makes them AMPHIPATHIC. This is what allows them to emulsify fats.
What is the FIRST step to making a bile acid? Include both names of the enzyme used. What does this step do? What energy is used to foster the reaction? Where is the enzyme found? What is the rate limiting step?
Cholesterol is converted to 7-alpha-hydroxycholesterol using the enzyme 7-alpha-hydroxylase = CYP7A1. This step adds OH to C7. It uses NADPH (converted to NADP). Enzyme is in the liver. Cholesterol presence is the rate limiting step. If it has a lot of cholesterol, it will make 7-alpha-hydroxycholeserol. If There is too much cholic acid present, the reaction will not go through (negative feedback).
What molecules does the liver use to conjugate cholic acid (or BA in general)? Compare the resulting pKa’s. What is the of adding these amino acids? What is another name for a conjugated bile acid?
Uses taurine (becomes taurocholic acid, pKa 2) or glycine (become glycocholic acid, pKa 4). Note pKa of cholic acid is 6. The goal is to make these bile acids more polar. These guys would be fully unprotonated (fully charged) at pH of 6. Note: these guys are officially bile salts when they lose their proton, and are thus charged.
At pH of 6, what is the status of cholic acid?
Half protonated and half unprotonated. The charge version is more hydrophilic.
Which of the following is the least soluble in water? cholesterol, cholic acid, chenodeoxylic acid, glycocholic acid. Which is the most hydrophilic?
- cholesterol (least polar)
2. glycocholic acid (most polar)
What makes BAs and BSs highly efficient detergents?
They help emulsify fats and fat-soluble vitamins. They also form mixed micelles essential for fat digestion and absorption. Breaks does fat globules into smaller fat droplets (emulsifies them) so that they can be digested by lipases. Without bile, you can’t absorb fats as well.
Describe the enterohepatic circulation of BAs.
When bile enters duodenum, runs through to distal ileum, most of the bile salts had been absorbed (90-95%) and sent to the liver then gallbladder for storage. This happens every time you eat. Can happen multiple times in one digestion. 5-10% of bile acids reach colon, where they are deconjugated and dehydroxylated by bacteria to become secondary bile acids.
Describe conversion process of primary to secdondary bile acids by gut bacteria.
- Remove conjugation (glysine, taurine, etc) (deconjugation). Becomes cholic acid and chenocholic acid
- Remove OH at C7 (dehydroxylation). Becomes deoxycholic acid and lithocholic acid (from chenocholic acid). These are now secondary bile acids…they are not something our body made…bacteria made it.
Which is more soluble in water? Cholesterol, primary bile acids, secondary bile acids?
CHolesterol = least solublem
Primary BA is most soluble due to conjugation. Secondary BA is in he middle because it lost the conjugation but still have more OH.
Where does hydroxylation and conjugation occur? Where does deconjugation and dehydroxylation occur?
- Liver, by hepatocytes
2. Colon, by bacteria
Difference between bile in our tissue and bile that is excreted?
Excreted bile lacks conjugations. We only use bile with conjugations added.
Lithocholic acid is a primary BA, secondary BA, or bile pigment?
Secondary BA.
When the distal ileum is removed, there will be an increase in bile acid: levels in hepatic venous blood, levels i portal venous blood, absorption by enterocytes, storage in gallbladder, synth by hepatocytes?
Synthesis by hepatocytes. Less distance for BS absorption, so the bile does not have as much space for absorption into the hepatic portal vein. So they get excreted more. Meaning, the liver has to make more bile to replace it. Level in portal venous blood would be lower. Less is stored in the gallbladder because the system is always using the bile that’s being made because the bile keeps getting excreted.
Consequences of ileal resections
- Bile salt pool shrinks (varies by dissection length)
- Fat malabsorption (due to less bile) and steatorrhea (fatty stool)
- Deficiency in fat soluble vitamins.
How do you manage patients who had an ileal resection?
- Limit dietary fat intake
2. Supplement diet with medium-chain triglycerides and fat soluble vitamins (ADEK)
What is the principal mech for eliminating cholesterol from body?
Excretion of BS.
What is the purpose of cholesterol?
- Steroid hormones
- BA, BS
- VItamin D
- Cell membrane
How is cholesterol eliminated in feces?
- As BA
- As unmodified cholesterol
- As a reduced cholesterol by bacteria (cholestanol and coprostanol)
