Skildum: Liver Biochem

Question 1

What type of cells are hepatic pit cells?

Answer 1

Natural killer lymphocytes!

Protect against viruses and tumor cells

Question 2

What are Phase I reactions?

Answer 2

The addition of a hydroxyl group to a xenobiotic!

1. Increase solubility
2. Add a potential reactive site to the molecule

Question 3

What do Phase II reactions do?

Answer 3

They conjugate another molecule to the xenobiotic! via the hydroxyl group;

Sulfate, methyl group, glutathione, or glucoronate

Question 4

What enzymes catalyze Phase I rxns?

Answer 4

Cyp450 enzymes

Question 5

What 2 things do all Cyp450 enzymes need?

Answer 5

NADPH

Oxygen

Question 6

What induces the expression of Cyp450 enzymes?

Answer 6

Their substrates!

*they have overlapping substrate specificity

Question 7

What does grapefruit juice contain that we have to keep in mind for drug metabolism?

Answer 7

Cyp3A4 inhibitor!

Question 8

If two statins are ingested, which one will be metabolized by Cyp3A4?

Answer 8

The one with the higher affinity

Question 9

_________ converts vinyl chloride to a reactive _______ that damages the liver.

This happens when the pool of __________ is low.

Answer 9

Cyp2E1

Epoxide

Reduced glutathione (for Phase II reactions)

Question 10

Most common cause of acute liver failure?

Answer 10

Acetaminophen toxicity

Question 11

What do sulfotransferases use as a sulfur donor?

Answer 11

PAPS

3’phosphoadenosine 5’phosphosulfate

Question 12

Ethanol induces the expression of what Cyp enzyme?

This increase the rate of production of what?

Answer 12

Cyp2E1

NAPQ1

Question 13

What does Cyp2E1 do?

Answer 13

Converts acetaminophen to NAPQI…this creates adducts on cell proteins and kills cells

Question 14

What drug can block Cyp2E1?

Answer 14

Cimetidine…an H2 antagonist

Question 15

What type of enzyme alters a xenobiotic so it can be excreted? (without it the xenobiotic is toxic)

Answer 15

Transferase

Question 16

What molecule is responsible for long term damage to the liver associated with ethanol consumption?

Answer 16

Acetaldehyde

Question 17

What is a major symptom of Glycogen storage diseases that affect the liver?

Answer 17

Fasting hypoglycemia

Question 18

Enzyme that intervonverts (both directions) Glucose-1-phosphate and glucose-6-phosphate?`

Answer 18

PGM1

Phosphoglucomutase 1

Question 19

Where do ureas 2 nitrogens come from?

Answer 19

Free ammonia

Aspartate

Question 20

In what form is excess nitrogen transported from peripheral tissues to the liver?

Answer 20

Glutamine

Alanine

Question 21

Describe what Acetaldehyde does to Kuppfer cells

Answer 21

Irritates them…they make cytokines, ROS, NO and activate the stellate cell to lay down collagen that impedes blood flow

Question 22

How is glutamine synthase expression regulated?

Answer 22

Glutamine synthase is transcriptionally acvtivated by beta catenin.

Question 23

Describe Wnt signaling!

Answer 23

Wnt interacts with the Frizzled receptor.

When Frizzled isn’t bound to Wnt, Beta-catenin gets phosphorylated and degraded by the proteosome.

When Wnt is around it inactivates the kinase that phosphorylates Beta-Catenin…goes into nucleus and regulates transcription!

Question 24

Where is glutamine synthase?

Answer 24

Perivenous hepatocytes

NOT periportal hepatocytes

Question 25

What cells secrete Wnt?

Answer 25

Central vein endothelial cells

Question 26

What enzyme is Wnt regulated?

Answer 26

Glutamine synthase

Question 27

Why does this whole Wnt pathway work the way it does in the liver?

Answer 27

Because free ammonia is a substrate for CPS1 but we don't want to let any ammonia get into the central vein!!

Question 28

The pentose phosphate pathway provides us with what 2 major things?

Answer 28

NADPH | Ribose

Question 29

What is done with the NADPH of the pentose phosphate pathway?

Answer 29

Used by Cyp enzymes to detoxify xenobiotics Used to synthesize and export cholesterol and tiracylglycerol

Question 30

Where does protein glycosylation occur?

Answer 30

lumen of ER

Question 31

What does glycosylation chain assembly begin on?

Answer 31

Dolichol

Question 32

Inheritance pattern of PGM1 deficiency?

Answer 32

Autosomal recessive

Question 33

What 2 major things is PGM1 essential for?

Answer 33

Glycogenolysis/glycogen synthesis Generating UDP-galactose--a glycosylation intermediate!

Question 34

What is an example of an important protein involved in iron regulation that has 2 glycosylated sites?

Answer 34

Transferrin

Question 35

What can elevated bilirubin mean?

Answer 35

Increased RBC breakdown OR Decreased conjugating capacity of liver

Question 36

How does bilirubin become conjugated?

Answer 36

It is glycosylated by the addition of 2 glucoronates in the form of UDP-glucoronate Enzyme= Glucoronosyl transferase

Question 37

Rate limiting step in bilirubin elimination?

Answer 37

Transport across canilicular membrane! | *Not conjugation

Question 38

What 3 things does NADPH gets used for?

Answer 38

FA synthesis Glutathione reduction CYP450 rxns

Question 39

2 main functions of PGM1?

Answer 39

Interconvert Glucose-1-phosphate and glucose-6-phosphate (glycogenolysis and glycogenogenesis) Generates UDP-Galactose--a glycosylation intermediate in the pathway for glycosylation of many other important things!

Question 40

ALT or AST more specific for liver damage?

Answer 40

ALT