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COM - GI Final > Liver Biochemistry > Flashcards

Liver Biochemistry Flashcards

1
Q

What are xenobiotic reactions?

A

Compounds w/no nutritional benefit but also may be toxic

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2
Q

What is the major role of the liver?

A

Monitor, synthesize, recycle, distribute, modify metabolites

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3
Q

How many acetyl CoAs make an IPP?

How many carbons is an IPP?

A

3

5

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4
Q

How is acetyl CoA generated and where?

A

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

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5
Q

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

A

Citrate shuttle

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6
Q

What makes up a sterane ring?

What is it the backbone of?

A

6 units of IPP forms 4-ring structure

Steroids (cholesterol, estradiol, cholic acid)

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7
Q

Where is the hydroxyl group located in cholesterol?

Double bond?

Where are the methyl groups located?

A

C3

Between C5-C6

C10 and C13

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8
Q

How many carbons does the sterane ring have?

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

A

17

17, 8

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9
Q

What is cholesterol a precursor to?

A

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

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10
Q

Describe phase 1 of cholesterol synthesis

A

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

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11
Q

Describe the phase 2 intermediates

A

6 IPP -> Squalene -> Lanosterol -> Cholesterol

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12
Q

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

A

HMG CoA -> Mevalonate

Enzyme is HMG CoA Reductase

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13
Q

What enzyme catalyzes Acetoacetyl CoA to HMG CoA?

A

HMG CoA synthase

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14
Q

What enzyme catalyzes the 1st step of cholesterol synthesis?

A

acetyl CoA - acetyltransferase

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15
Q

What stimulates the formation of Mevalonate?

A

Insulin

Thyroxine

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16
Q

What inhibits the formation of Mevalonate?

A 
Vit E
high AMP
glucagon
sterols and statins
VAGSS
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17
Q

How is cholesterol packaged and where does it go?

A

Into VLDLs and released into circulation

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18
Q

How is cholesterol used in the liver?

Skin?

Adrenals, ovaries, testes?

A

Synthesize bile acids

Synthesize Vit D

Synthesize steroid hormones

19
Q

Where is cholesterol located?

What kind of density?

Local centers for what?

A

Lipid rafts

Low buoyant density

Signal transduction processes

20
Q

Where are the sites of ubiquination of HMG-CoA Reductase

Which side does the catalytic domain face?

A

Lys 89 and 248

cytosol

21
Q

How is HMG CoA Reductase inhibited?

What is a competitive inhibitor of it?

A

Free F.A., bile acids, oxysterols
FBO

statins

22
Q

When is HMG CoA Reductase active?

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

A

Dephosphorylated

Insulin
HMGR phosphatase

23
Q

What inactivates HMG CoA Reductase?

A

Low energy/high AMP

Glucagon (prevents dePO4)

24
Q

Where is the SRE located?

Where does it bind?

A

Promoter

SREBP

25
Q

What does the SREBP bind to?

In the presence of cholesterol what happens to this complex?

A

SCAP

Retained in ER due to binding to INSIG, SLOW transcription

26
Q

How is HMG CoA Reductase translationally regulated?

A

Reduced by gamma-tocotrienol (Vit E) and oxylanosterols

27
Q

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

A

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

28
Q

How is degradation of HMG enhanced?

A

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

29
Q

How are dietary cholesterols delivered to the liver?

A

Chylomicron remnants

30
Q

What is the liver a major source of?

What does it synthesize?

A

Nascent HDLs

Bile acids, eliminates cholesterol into bile

31
Q

What are the side effects of statins?

What is the Ki for statins?

A

Myotoxic - decreased formation of ubiquonone and prenylated proteins

5-45 nM

32
Q

What else can CYPs do?

A

Detoxify xenobiotics and statins

33
Q

What do agents that inhibit CYP cause?

Examples of CYP inhibitors?

A

INC in statin levels -> toxic side effects

Clarithromycin, itraconozole, cycolsporine
Citrus juice, grapefruit juice

34
Q

What enzyme degrades sterane ring of cholesterol?

What is cholesterol converted to?

A

NONE

Bile acids

35
Q

Where is bile made?

What is a precursor to bile acids and salts?

A

Hepatocytes

Hepatic cholesterol

36
Q

Fx of bile?

A

Lipid emulsifier, aids in lipid digestion by forming micelles

37
Q

Describe the synthesis of bile acids starting with cholesterol

A

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

3a,7a,12a-Triol -> cholic acid

38
Q

Where are the OH groups located on Chenocholic acid?

A

C3 and 7

39
Q

Cholic is conjugated to what?

What is added?

Final end products?

A

Cholyl CoA

Taurine and Glycine

Taurocholic acid and Glycocholic acid

40
Q

Where are the OH groups located on cholic acid?

A

C3, 7, 12

41
Q

What are gallstone crystals made of?

What is cholelithiasis?

A

Bile supersaturated with cholesterol

Insufficient secretion of bile salts or phospholipids OR excess cholesterol secretion

42
Q

What is the Tx of gallstones?

A

Oral ursodeoxcholic acid (2ndary bile acid) reduces cholesterol secretion into bile

For small-medium sized stones

43
Q

How does the liver get its blood?

A

75% portal V via enteric circulation

25% hepatic A via periphery

44
Q

CYP enzymes are needed to convert what into what?

A

Linear isoprenoid Squalene into cholesterol

COM - GI Final (5 decks)

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