Liver Biochemistry

Question 1

What are xenobiotic reactions?

Answer 1

Compounds w/no nutritional benefit but also may be toxic

Question 2

What is the major role of the liver?

Answer 2

Monitor, synthesize, recycle, distribute, modify metabolites

Question 3

How many acetyl CoAs make an IPP?

How many carbons is an IPP?

Answer 3

3

5

Question 4

How is acetyl CoA generated and where?

Answer 4

In mitochondria via
Oxidative de carboxylation of pyruvate
Beta oxidation of F.A.
Breakdown of a.a.

Question 5

Biosynthesis occurs in the cytosol, how is acetyl CoA transported there?

Answer 5

Citrate shuttle

Question 6

What makes up a sterane ring?

What is it the backbone of?

Answer 6

6 units of IPP forms 4-ring structure

Steroids (cholesterol, estradiol, cholic acid)

Question 7

Where is the hydroxyl group located in cholesterol?

Double bond?

Where are the methyl groups located?

Answer 7

C3

Between C5-C6

C10 and C13

Question 8

How many carbons does the sterane ring have?

Where is the hydrocarbon side chain attached and how many carbons?

Answer 8

17

17, 8

Question 9

What is cholesterol a precursor to?

Answer 9

Bile acids and bile salts
Vitamin D
Steroid hormones (alcohols)

Question 10

Describe phase 1 of cholesterol synthesis

Answer 10

Acetyl CoA -> Acetoacetyl CoA -> HMG CoA -> Mevalonate -> IPP

Question 11

Describe the phase 2 intermediates

Answer 11

6 IPP -> Squalene -> Lanosterol -> Cholesterol

Question 12

What is the RLS of cholesterol synthesis and what is the substrate and product?

Answer 12

HMG CoA -> Mevalonate

Enzyme is HMG CoA Reductase

Question 13

What enzyme catalyzes Acetoacetyl CoA to HMG CoA?

Answer 13

HMG CoA synthase

Question 14

What enzyme catalyzes the 1st step of cholesterol synthesis?

Answer 14

acetyl CoA - acetyltransferase

Question 15

What stimulates the formation of Mevalonate?

Answer 15

Insulin

Thyroxine

Question 16

What inhibits the formation of Mevalonate?

Answer 16

Vit E
high AMP
glucagon
sterols and statins
VAGSS

Question 17

How is cholesterol packaged and where does it go?

Answer 17

Into VLDLs and released into circulation

Question 18

How is cholesterol used in the liver?

Skin?

Adrenals, ovaries, testes?

Answer 18

Synthesize bile acids

Synthesize Vit D

Synthesize steroid hormones

Question 19

Where is cholesterol located?

What kind of density?

Local centers for what?

Answer 19

Lipid rafts

Low buoyant density

Signal transduction processes

Question 20

Where are the sites of ubiquination of HMG-CoA Reductase

Which side does the catalytic domain face?

Answer 20

Lys 89 and 248

cytosol

Question 21

How is HMG CoA Reductase inhibited?

What is a competitive inhibitor of it?

Answer 21

Free F.A., bile acids, oxysterols
FBO

statins

Question 22

When is HMG CoA Reductase active?

What factors favor activation?
-What enzyme does this activator work through?

Answer 22

Dephosphorylated

Insulin
HMGR phosphatase

Question 23

What inactivates HMG CoA Reductase?

Answer 23

Low energy/high AMP

Glucagon (prevents dePO4)

Question 24

Where is the SRE located?

Where does it bind?

Answer 24

Promoter

SREBP

Question 25

What does the SREBP bind to? In the presence of cholesterol what happens to this complex?

Answer 25

SCAP Retained in ER due to binding to INSIG, SLOW transcription

Question 26

How is HMG CoA Reductase translationally regulated?

Answer 26

Reduced by gamma-tocotrienol (Vit E) and oxylanosterols

Question 27

In cases of high cholesterol what happens to the HMG CoA Reductase?

Answer 27

Interacts with INSIG --> polyubiquination --> removal from ER and degradation by 26S protea some

Question 28

How is degradation of HMG enhanced?

Answer 28

Sterols, methylated sterols, oxysterols, to orients, Mevalonate derivatives, Biphosphate SR-12813

Question 29

How are dietary cholesterols delivered to the liver?

Answer 29

Chylomicron remnants

Question 30

What is the liver a major source of? What does it synthesize?

Answer 30

Nascent HDLs Bile acids, eliminates cholesterol into bile

Question 31

What are the side effects of statins? What is the Ki for statins?

Answer 31

Myotoxic - decreased formation of ubiquonone and prenylated proteins 5-45 nM

Question 32

What else can CYPs do?

Answer 32

Detoxify xenobiotics and statins

Question 33

What do agents that inhibit CYP cause? Examples of CYP inhibitors?

Answer 33

INC in statin levels -> toxic side effects Clarithromycin, itraconozole, cycolsporine Citrus juice, grapefruit juice

Question 34

What enzyme degrades sterane ring of cholesterol? What is cholesterol converted to?

Answer 34

NONE Bile acids

Question 35

Where is bile made? What is a precursor to bile acids and salts?

Answer 35

Hepatocytes Hepatic cholesterol

Question 36

Fx of bile?

Answer 36

Lipid emulsifier, aids in lipid digestion by forming micelles

Question 37

Describe the synthesis of bile acids starting with cholesterol

Answer 37

Cholesterol -> 7alpha-hydroxycholesterol -> 3a,7a-Diol -> Chenocholic acid 3a,7a,12a-Triol -> cholic acid

Question 38

Where are the OH groups located on Chenocholic acid?

Answer 38

C3 and 7

Question 39

Cholic is conjugated to what? What is added? Final end products?

Answer 39

Cholyl CoA Taurine and Glycine Taurocholic acid and Glycocholic acid

Question 40

Where are the OH groups located on cholic acid?

Answer 40

C3, 7, 12

Question 41

What are gallstone crystals made of? What is cholelithiasis?

Answer 41

Bile supersaturated with cholesterol Insufficient secretion of bile salts or phospholipids OR excess cholesterol secretion

Question 42

What is the Tx of gallstones?

Answer 42

Oral ursodeoxcholic acid (2ndary bile acid) reduces cholesterol secretion into bile For small-medium sized stones

Question 43

How does the liver get its blood?

Answer 43

75% portal V via enteric circulation | 25% hepatic A via periphery

Question 44

CYP enzymes are needed to convert what into what?

Answer 44

Linear isoprenoid Squalene into cholesterol