Liver Biochem

Question 1

functions of the liver (7)

Answer 1

1) lipid biosynthesis and management (triacylglycerol, phospholipids, steroids
2) protein biosynthesis: albumin, IgG
3) nitrogen metabolism: urea cycle
4) waste management: xenobiotic reactions
5) Bilirubin metabolism
6) fuel management
7) primary receiving, distribution and recycling center

Question 2

structural features of liver

Answer 2

no basement membrane
gaps between endothelial cells
fenestrations in endothelial cells
low portal blood pressure
all allow greater access and increased contact between liver and blood

Question 3

hepatocyte features

Answer 3

well developed plasma membrane with endocytic and exocytic system

well developed ER (rough and smooth)

metabolically active cells

lots of mitochondria and lysosomes

Question 4

what is used to generate isopentenyl pyrophosphate (IPP)

Answer 4

3 acetyl coA makes 5-C IPP

Question 5

IPP is building block for what?

Answer 5

1) steroids: cholesterol, bile acids, steroid hormones
2) lipid-soluble vitamins: ADEK
3) other: ubiquinone, dolichol, heme tails, lipid anchors

Question 6

sources of acetyl CoA

Answer 6

from mitochondria

1) beta oxidation FA
2) oxidative decarboxylation of pyruvate
3) breakdown of amino acids

-transported into cytoplasm via citrate shuttle

Question 7

six units of IPP form what?

Answer 7

tetracyclic (4-ring) sterane backbone of most steroids

Question 8

cholesterol structure

Answer 8

• sterane ring has 17-C
  
  • sidechain has 8 hydrocarbons attached at C17
  • methyl groups at C10 and C13
  • hydroxyl group at C3
  • 1 double bond between C5 and C6

Question 9

cholesterol is precursor of what compounds (3 categories on this card)

Answer 9

bile acids and bile salts
vitamin D
steroid hormones ( progesterone, aldosterone, cortisol, testosterone, estradiol)

Question 10

what is the synthesis of cholesterol regulated by?

Answer 10

dietary intake

Question 11

compounds derived from intermediates in cholesterol synthesis

Answer 11

quinol form of ubiquinone CoQ10

Heme A

Question 12

cholesterol is packaged into ____ and released into circulation

Answer 12

VLDL

Question 13

fate of cholesterol in all tissues

Answer 13

incorporated into cell membranes

Question 14

fate of cholest in liver

Answer 14

used to synthesize bile acids

Question 15

fate of cholesterol in adrenal glands, ovaries, and testes

Answer 15

used to synthesize steroid hormones

Question 16

fate of cholesterol in skin

Answer 16

used to synthesize vitamin D

Question 17

lipid rafts

Answer 17

PM microdomains enriched in cholest, sphingolipids, and gangliosides

-detergent insoluble

local center for signal transduction processes

sites for abnormal processing of proteins in neurodegenerative disorders

Question 18

direct inhibition of HMG CoA reductase

Answer 18

inhibited by free fatty acids, bile acids, and oxysterols

-also inhbited by statins, which are competitive inhibtors of the enzyme

Question 19

HMG CoA Reductase covalent mods active

Answer 19

active when dephos, inactive when phosphorylated

-conditions of low energy with high AMP stimulates AMPK which phosphorylates and inactivates it

Glucagon inhibits enzyme by preventing dephosphorylation

insulin activates enzyme by promoting dephosphorylation

Question 20

insulin activates what which activates HMGR

Answer 20

HMGR phosphatase

Question 21

translation of HMG CoA reductase is reduced by what

Answer 21

gamma-tocotrienol (vitamin E family) and oxylanosterols

Question 22

liver packages cholesterol into ___ which is released into blood and metabolized to ___ by peripheral tissues

Answer 22

VLDL to LDL

Question 23

liver is a major source of nascent ___ which does what

Answer 23

HDLs which helps to clear the bulk of lipoproteins from the blood

Question 24

myotoxic side effects of statins

Answer 24

decreased formation of ubiquinone and prenylated proteins

Question 25

cytochrome P450 enzymes convert

also detoxify?

Answer 25

linear isoprenoid squalene into cholesterol

- also detoxify xenobiotics and pharmacological agents (including statins)

Question 26

agents that inhibit CYP (cytochrome P450) cause what

Answer 26

increase in statin levels leading to toxic side effects

-clarithromycin, itraconozole, cyclosporine, citrus juices, grapefruit juice

Question 27

agents that induce CYP

Answer 27

decrease levels of statin in plasma

-rifampicin, carbamazepine, and st john’s wort

Question 28

elimination of cholesterol

Answer 28

no enzyme can degrade sterane ring of cholesterol
cholest can be converted to bile acids and stored in bile
some cholesterol and bile are excreted in feces