6. Liver Biochemistry

Question 1

What is the precursor to cholesterol, lipid soluble vitamins, and other steroids?

Answer 1

Isopentenyl pyrophosphate (IPP).

Question 2

What three methods are there for the generation of acetyl CoA?

Answer 2

Oxidative decarboxylation of pyruvate.

Breakdown of fatty acids (beta oxidation).

Breakdown of amino acids.

Question 3

What is the general function of phase II of xenobiotic detoxification?

How might this be accomplished?

Answer 3

Making the molecule safer, so that it can travel to the kidney.

Conjugation with sulfates, methyl groups, or glucuronides.

Question 4

What antifungal drugs inhibit what step in cholesterol synthesis?

Answer 4

The “azoles” inhibit the conversion of lanosterol to cholesterol.

Question 5

What is the general function of phase I of xenobiotic detoxification?

How might this be accomplished?

Answer 5

Increasing the polarity of the molecule.

Reduction, oxidation, hydroxylation, hydrolysis.

Question 6

Besides statins, what other molecules stimulate and inhibit HMG-CoA reductase?

Answer 6

Upregulate: insulin.

Inhibit: glucagon, AMP, vitamin E, sterols, thyroxine.

Question 7

What is the rate limiting step of bile acid synthesis?

Answer 7

Cholesterol is hydroxylated at the seventh carbon by 7alpha-hydroxylase.

Question 8

What is the name for the natural killer cells of the liver?

Answer 8

Pit cells.

Question 9

What secondary bile acid corresponds to each of the two primary bile acids?

Answer 9

Cholic acid = deoxycholic acid.

Chenodeoxycholic acid = lithocolic acid.

Question 10

Why might someone on a statin experience lethargy?

Answer 10

Statins inhibit HMG-CoA reductase, which produces isopentenyl pyrophosphate, which is used to make ubiquinone – a part of the electron transport chain in mitochondria.

Question 11

Statins inhibit what vital enzyme in cholesterol synthesis?

Answer 11

HMG-CoA reductase.

Question 12

What is the general, most basic, overall cause for gallstones?

Answer 12

Too much cholesterol, or too little bile salts.

Question 13

Where is acetyl COA generated?

Where does cholesterol biosynthesis occur?

What is the shuttle between those two locations?

Answer 13

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.

Question 14

How do statins indirectly increase the reuptake of LDLs from the bloodstream?

Answer 14

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.

Question 15

What is isopentenyl pyrophosphate made of?

Answer 15

Three acetyl COA molecules.

Question 16

What are the basic steps to get from cholesterol to cholic acid?

Answer 16

Cholesterol -> (7alpha-hydroxylase/addition of a hydroxyl group) -> 7alpha-hydroxycholesterol -> (addition of a carboxyl group) -> chenodeoxycholic acid -> (addition of a hydroxyl group) -> cholic acid.

Question 17

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?

Answer 17

It is called a sterane ring, and is made of six units of isopentenyl pyrophosphate.

Question 18

What is the general pathway from acetyl COA to isopentenyl pyrophosphate?

Answer 18

Acetyl CoA + acetoacetyl-CoA -> (HMG-CoA synthase) -> HMG-CoA

HMG-CoA -> (HMG-CoA reductase) -> mevalonate

mevalonate -> isopentenyl pyrophosphate

Question 19

What is the function of hepatic stellate cells?

Answer 19

Storage of vitamin A and other lipids.

Question 20

What all can be made from isopentenyl pyrophosphate?

Answer 20

“Isoprenoids”

Steroids, cholesterol, bile salts, lipid soluble vitamins (A, D, E, K), ubiquinone – among others.

Question 21

What to amino acids can be conjugated with chenodeoxycholic acid and cholic acid?

Answer 21

Taurine and glycine.

Question 22

What three specific things about the structure of cholesterol did Dr. Zaidi ask us to remember?

Answer 22

It has a hydrocarbon chain, it has a sterane ring, and it has a hydroxyl group at carbon three.

Question 23

What are secondary bile acids?

Answer 23

The remnants of bile acids after commensal bacteria remove the glycine/taurine and a hydroxyl group.

Question 24

What is the general pathway from isopentenyl pyrophosphate to cholesterol?

Answer 24

Isopentenyl pyrophosphate (6) -> squalene -> lanosterol -> cholesterol.

Question 25

What are the two main possible products of initial synthesis of bile acids?

Answer 25

Chenodeoxycholic acid and cholic acid.