6. Liver Biochemistry Flashcards
What is the precursor to cholesterol, lipid soluble vitamins, and other steroids?
Isopentenyl pyrophosphate (IPP).
What three methods are there for the generation of acetyl CoA?
Oxidative decarboxylation of pyruvate.
Breakdown of fatty acids (beta oxidation).
Breakdown of amino acids.
What is the general function of phase II of xenobiotic detoxification?
How might this be accomplished?
Making the molecule safer, so that it can travel to the kidney.
Conjugation with sulfates, methyl groups, or glucuronides.
What antifungal drugs inhibit what step in cholesterol synthesis?
The “azoles” inhibit the conversion of lanosterol to cholesterol.
What is the general function of phase I of xenobiotic detoxification?
How might this be accomplished?
Increasing the polarity of the molecule.
Reduction, oxidation, hydroxylation, hydrolysis.
Besides statins, what other molecules stimulate and inhibit HMG-CoA reductase?
Upregulate: insulin.
Inhibit: glucagon, AMP, vitamin E, sterols, thyroxine.
What is the rate limiting step of bile acid synthesis?
Cholesterol is hydroxylated at the seventh carbon by 7alpha-hydroxylase.
What is the name for the natural killer cells of the liver?
Pit cells.
What secondary bile acid corresponds to each of the two primary bile acids?
Cholic acid = deoxycholic acid.
Chenodeoxycholic acid = lithocolic acid.
Why might someone on a statin experience lethargy?
Statins inhibit HMG-CoA reductase, which produces isopentenyl pyrophosphate, which is used to make ubiquinone – a part of the electron transport chain in mitochondria.
Statins inhibit what vital enzyme in cholesterol synthesis?
HMG-CoA reductase.
What is the general, most basic, overall cause for gallstones?
Too much cholesterol, or too little bile salts.
Where is acetyl COA generated?
Where does cholesterol biosynthesis occur?
What is the shuttle between those two locations?
Acetyl COA is generated in the mitochondria.
Cholesterol biosynthesis occurs in the cytoplasm.
The citrate shuttle moves acetyl CoA from the mitochondria to the cytoplasm.
How do statins indirectly increase the reuptake of LDLs from the bloodstream?
The low-cholesterol environment causes INSIG to dissociate from SCAP, which causes SCAP to dissociate from SREBP.
This causes SREBP to release its N-terminus, which acts as a transcription factor for LDL-receptors. This then increases LDL-receptor mediated endocytosis.
What is isopentenyl pyrophosphate made of?
Three acetyl COA molecules.
What are the basic steps to get from cholesterol to cholic acid?
Cholesterol -> (7alpha-hydroxylase/addition of a hydroxyl group) -> 7alpha-hydroxycholesterol -> (addition of a carboxyl group) -> chenodeoxycholic acid -> (addition of a hydroxyl group) -> cholic acid.
Isopentenyl pyrophosphate forms a common backbone for most steroids. What is that common backbone called, and how many IPP molecules are needed to form it?
It is called a sterane ring, and is made of six units of isopentenyl pyrophosphate.
What is the general pathway from acetyl COA to isopentenyl pyrophosphate?
Acetyl CoA + acetoacetyl-CoA -> (HMG-CoA synthase) -> HMG-CoA
HMG-CoA -> (HMG-CoA reductase) -> mevalonate
mevalonate -> isopentenyl pyrophosphate
What is the function of hepatic stellate cells?
Storage of vitamin A and other lipids.
What all can be made from isopentenyl pyrophosphate?
“Isoprenoids”
Steroids, cholesterol, bile salts, lipid soluble vitamins (A, D, E, K), ubiquinone – among others.
What to amino acids can be conjugated with chenodeoxycholic acid and cholic acid?
Taurine and glycine.
What three specific things about the structure of cholesterol did Dr. Zaidi ask us to remember?
It has a hydrocarbon chain, it has a sterane ring, and it has a hydroxyl group at carbon three.
What are secondary bile acids?
The remnants of bile acids after commensal bacteria remove the glycine/taurine and a hydroxyl group.
What is the general pathway from isopentenyl pyrophosphate to cholesterol?
Isopentenyl pyrophosphate (6) -> squalene -> lanosterol -> cholesterol.
What are the two main possible products of initial synthesis of bile acids?
Chenodeoxycholic acid and cholic acid.
