Liver Biochemistry Flashcards
75% of the liver blood supply comes from what blood vessel?
25% of the liver blood supply comes from what blood vessel?
75% Portal V.
25% Proper Hepatic A.
Which of the following makes up 80% of the cells of the liver, and responsible for carrying out metabolic liver functions?
A. Kupffer cells
B. Hepatic Stellate cells
C. Pit cells
D. Cholangiocytes
E. Hepatocytes
Hepatocytes
NOTE: these cells also have regeneration capabilities
Which of the following are responsible for removing damaged blood vessels?
A. Kupffer cells
B. Hepatic Stellate cells
C. Pit cells
D. Cholangiocytes
E. Hepatocytes
A. Kupffer cells
Which of the following liver cells are best for protecting against viruses and tumor cells?
A. Kupffer cells
B. Hepatic Stellate cells
C. Pit cells
D. Cholangiocytes
E. Hepatocytes
Pit cells
Pit cells are Natural Killer Cells
Which of the following liver cells are responsible for controlling bile flow rate and bile pH?
A. Kupffer cells
B. Hepatic Stellate cells
C. Pit cells
D. Cholangiocytes
E. Hepatocytes
Cholangiocytes
- line the bile ducts
Which of the following liver cells serve as storage for Vitmaine A and other lipids
A. Kupffer cells
B. Hepatic Stellate cells
C. Pit cells
D. Cholangiocytes
E. Hepatocytes
Hepatic Stellate cells
Liver recieves blood from both the ______ circulation via the portal vein, and from ________ circulation via the hepatic artery
Liver recieves blood from both the enteric circulation via the portal vein, and from peripheral circulation via the hepatic artery
What are 3 structural adaptations allow greater access and contact b/w liver and blood?
Gap Junctions (b/w endothelial cells)
Fenestrations (in endothelial cell membrane)
Lacks a basement membrane
Bile acids are the _____ form, while bile salts are the ______ form.
A. Protonated; deprotonated
B. conjugated; unconjugated
C. Deprotonated; protonated
D. polar; non-polar
Protonated; deprotonated
Bile acids are the protonated form, while bile salts are the deprotonated form.
Bile acids are made from hepatic cholesterol in what liver cells?
Hepatocytes
Describe the emulsification of bile salts starting with cholic acid
- Cholic acid ionizes to form its conjugate bile salts
- the hydrophobic surface of the bile salt associates with the TAG and forms a micelle
- The hydrophilic surface faces outward and allows micelle to associate with pancreatic lipase/collipase
- The lipase/collipase frees FAs into smaller micelles that can be absorbed
The commited step of the synthesis of bile acids is the conversion of cholesterol –> 7a-Hydroxycholesterol.
What enzyme catalyzes this step and what does it do?
The presence of what substance inhibits the enzyme?
7a-hydroxylase; adds hydroxyl group to C7 site
Bile acids
NOTE: this enzyme is present in the ER (cytoplasm) of hepatocytes
Reduction, hydroxylation, and conversion of hydroxyls to alpha, transforms 7a-hydroxycholesterol to what 3a,7a-diol?
Oxidation of the side chain of the 3a,7a-diol produces what 3a,7a,12a-Triol?
Chenodeoxycholic acid
Cholic acid
Before bile acids are secreted, they are conjugated in order to become better emulsifying agents. When cholic acid is converted to Cholyl CoA, it has a pKa of 6, which isn’t good enough to yield a detergent effect in the intestines. List the two substances that are used to conjugate cholic acid, indicate the final product, and include their pkAs.
Taurine -> Taurocholic acid pKa 2
Glycine -> Glycocholic acid pKa 4
NOTE: 3:1 in favor of glycine
What are the two conjugated products of chenodeoxycholic acid when using taurine or glycine?
Taurochenodeoxycholic acid
Glycochenodeoxycholic acid
A mad genious makes a new conjugated bile acid with a pKa of 3, and calls it “Sauce”. From strongest to weakest, what would be the correct order of the following bile acids
A. Cholic acid > chenodeoxycholic acid > Taurocholic acid > Sauce
B. Taurocholic acid > Glycocholic acid > Sauce > Cholic acid
C. Taurocholic acid > Sauce > Glycocholic acid > Cholic Acid
D. None of the above
Taurocholic acid > Sauce > Glycocholic acid > Cholic Acid
Primary bile salts are used in the duodenum to emulsify dietary lipds to aid in thier digestion and absorption. What process is then used later in the ileum to turn primary bile salts into secondary or primary bile acids?
A. Bacteria cojugate and hydroxylate
B. Viruses deconjugate and dehydroxylate
C. Bacteria deconjugate and hydroxylate
D. Bacteria deconjugate and dehydroxylate
Bacteria deconjugate and dehydroxylate
What is the name of the Secondary bile acids derived from cholic acid?
What is the name of the secondary bile acid derived from chenodeoxycholic acid?
Deoxycholic acid
Lithocholic acid
Pay attention because the deoxycholic is not from chenodeoxycholic acid
What is the non-absorbable bile-acid binding resins that causes a large increase in excretion of bile acids, because it converts them to a form that cannot be absorbed?
A. 7a-hydroxylase
B. statin
C. cholestyramine
D. pancreatic lipase
cholestyramine
What is the effect of cholestyramine on 7a-hydroxylase? How does this interaction end up lowering plasma cholesterol levels?
Cholestyramine induces 7a-hydroxylase to incerase the rate of bile acid synthesis. This increase in bile acid synthesis depletes the liver’s cholesterol pool and increases the uptake of LDL by the liver, leading to lower plasma cholesterol levels
NOTE: this is why cholestyramine is a good alternative for folks who can’t take statins
Which of the following correctly describes cholelithiasis?
A. Insufficient secretion of bile salts or phospholipids into the gallbladder
B. Crystals made of bile supersaturated with cholesterol
C. Excess cholesterol secretion into bile
D. A malabsorption syndrome and deficinecy in fat soluble vitamins
E. A and C
A and C
Insufficient secretion of bile salts or phospholipids into the gallbladder
Excess cholesterol secretion into bile
NOTE: cholelithiasis can cause gallstones to develop
The liver is the primary site for conversion and degredation of metabolites and xenobiotics. Which of the following correctly describes xenobiotics?
A. Ingested compounds with high nutritional non-toxic value
B. Ingested compounds with no nutritional value or potentially toxic
C. Compounds made in the body
D. None of the above
Ingested compounds with no nutritional value or potentially toxic
The liver does inactivation and detoxification of xenobiotics, in a reaction that’s completed in 2 phases. What happens in phase 1 and phase 2, include any relevant enxymes?
Phase I: increase polarity of substnce using CYP enzyme
Phase 2: add a functional group to conjugate the substance for safe excretion
What are the 4 potential reactions that increase the polarity of the metobolite in Phase I of xenobiotic detoxification?
Reduction
Oxidation
Hydroxylation
Hydrolysis
What are the possible reactions in phase 2 of xenobiotic detoxification that form the secondary metabolite that’s safe and suitable for excretion?
Conjugation
Sulfation
Methylation
Glucuronidation
Come See Me Glock
NOTE: we add a functional group, so if it sounds like it’s adding somethinng (i.e. methyl-, sulfa- ation) that’s probs the one
T/F: Drug metabolism in the liver is due to liver enzymes having low substrate specificity
True
CYPs colocalize with NADPH and make which of the following rate-limiting enzymes?
A. cytochrome P450 reductase
B. CYPR
C. CYP
D. A and B
A and B
cytochrome P450 reductase is CYPR
Cytochrome P450 enzymes (CYPs) are a superfamily made of 18 families, but only 3 are responsible for most of the phase 1 drug metabolism. What are those 3 CYPs?
CYP 1, CYP2, CYP3
Taking a statin with which of the following would form a stable interaction with a CYP, causing it to inhibit the metabolism of statin so that we see more statin in the plasma?
A. Rifampicin
B. St. John’ s Wort
C. Carbamazepine
D. Grapefruit juice
Grapefruit juice
Taking a statin with which of the following would induce CYP, causing us to see less statin in the plasma?
A. Cyclosporin
B. Rifampcin
C. Itraconozole
D. Citrus juices
E. Clarithromycin
Rifampcin
What are the 5 CYP inhibitors Dr. Zaidi shared, and said would cause increased levels of drugs seen in the plasma?
Itraconozole
Clarithromycin
Cyclosporin
Citrus Juice
Grapefruit juice
Citrus and Grapfruit, It Clogs Cyps
What are the 3 CYP inducers that Dr. Zaidi shared and said would cause us to see decreased levels of drugs in the plasma?
Rifampcin
Carbamazepine
St. Johns Wort
In an acetominophen overdose, the livers capacity for normal conjugation gets overwhelemed, and instead acetominophen gets oxidized by CYP3A4 to become what product that produces free radicals that damage hepatocytes?
A. N-acetyl benzoquinoneimine (NABQ1)
B. Glutathione
C. N-acetyl cysteine
D. Sulphydryl compound
E. C and D
N-acetyl benzoquinoneimine (NABQ1)
In an acetominophen overdose, the livers capacity for normal conjugation gets overwhelemed, and instead acetominophen gets oxidized by CYP3A4 to a free radical producing compound. Which of the following compounds is stored in the liver, and becomes depleted during this overdose due to its ability to detoxify the substance?
A. N-acetyl benzoquinoneimine (NABQ1)
B. Glutathione
C. N-acetyl cysteine
D. Sulphydryl compound
E. C and D
Glutathione
Which of the following can be given as an antidote to acetominophin poisoning?
A. N-acetyl benzoquinoneimine (NABQ1)
B. Glutathione
C. N-acetyl cysteine
D. A Sulphydryl compound
E. C and D
C and D
N-acetyl cysteine is a Sulphydryl compound
What are the two transaminases that are involved in the interconversion of AAs and ketoacids and are located in the mitochondria. These transaminases are normally found in the liver, but if they are found in the blood you know the liver is having issues.
Indicate which one is more sensitive in biochemical testing due to it’s location in both the mitochondria and cytosol?
ALT (alanine transaminase)- more sensitive
AST (aspartate transaminase)
