Liver Biochem 1&2 - Skildum

Question 1

How do N-acetyl cystein fight acetaminophen toxicity?

Answer 1

It increases glutathione-s-transferase. This enzyme converts NAPQUI to Mercaptouric acid

Question 2

How does alcohol affect acetaminophen toxicity?

Answer 2

It lowers the threshold for toxicity. EtOH increases CYP2E1 activation, which causes more acetaminophen to be converted into NAPQI, the toxic metabolite.

Question 3

ACetaldehyde produced by ADH and CYP2E1 is responsible for long-term liver damage from EtOH use.
What happens between Kupffer and Stellate cells for this to occur?

Answer 3

• Kupffer cell is activated by acetaldehyde
• Activated Kupffer cell stimulates stellate cell to lose its Vitamin A and grab some collagen
• Deposition of these cells creates fibrosis and cirrhosis

Question 4

We all know glutamine is what carries excess nitrogen from protein breakdown that the body wants to excrete. What two enzymes in the liver are necessary to remove and prepare the nitrogen for excretion? Periportally located or perivenous?

Answer 4

Glutaminase and CPS-1

Their expression is highest periportally

Question 5

What enzyme is found perivenously so that it can be used if NH4 is overwhelming the liver’s capacity to prepare it for excretion? Located where?

Answer 5

Glutamine synthetase is located perivnously in order to convert free NH4 back into glutamine, in order to avoid NH$ toxicity when the enzymes are overwhelmed.

Question 6

Wnt is found in a gradient in the liver. Where are concentrations highest and lowest? What is the mechanistic reason for that?

Answer 6

Wnt is found in increased amounts perivenously.

Wnt can then act on cells to stabilize beta-catenin and allow transcription of genes that will make glutamine synthetase!