Liver Biochem Flashcards
functions of the liver (7)
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
structural features of liver
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
hepatocyte features
well developed plasma membrane with endocytic and exocytic system
well developed ER (rough and smooth)
metabolically active cells
lots of mitochondria and lysosomes
what is used to generate isopentenyl pyrophosphate (IPP)
3 acetyl coA makes 5-C IPP
IPP is building block for what?
1) steroids: cholesterol, bile acids, steroid hormones
2) lipid-soluble vitamins: ADEK
3) other: ubiquinone, dolichol, heme tails, lipid anchors
sources of acetyl CoA
from mitochondria
1) beta oxidation FA
2) oxidative decarboxylation of pyruvate
3) breakdown of amino acids
-transported into cytoplasm via citrate shuttle
six units of IPP form what?
tetracyclic (4-ring) sterane backbone of most steroids
cholesterol structure
- 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
cholesterol is precursor of what compounds (3 categories on this card)
bile acids and bile salts
vitamin D
steroid hormones ( progesterone, aldosterone, cortisol, testosterone, estradiol)
what is the synthesis of cholesterol regulated by?
dietary intake
compounds derived from intermediates in cholesterol synthesis
quinol form of ubiquinone CoQ10
Heme A
cholesterol is packaged into ____ and released into circulation
VLDL
fate of cholesterol in all tissues
incorporated into cell membranes
fate of cholest in liver
used to synthesize bile acids
fate of cholesterol in adrenal glands, ovaries, and testes
used to synthesize steroid hormones
fate of cholesterol in skin
used to synthesize vitamin D
lipid rafts
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
direct inhibition of HMG CoA reductase
inhibited by free fatty acids, bile acids, and oxysterols
-also inhbited by statins, which are competitive inhibtors of the enzyme
HMG CoA Reductase covalent mods active
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
insulin activates what which activates HMGR
HMGR phosphatase
translation of HMG CoA reductase is reduced by what
gamma-tocotrienol (vitamin E family) and oxylanosterols
liver packages cholesterol into ___ which is released into blood and metabolized to ___ by peripheral tissues
VLDL to LDL
liver is a major source of nascent ___ which does what
HDLs which helps to clear the bulk of lipoproteins from the blood
myotoxic side effects of statins
decreased formation of ubiquinone and prenylated proteins
cytochrome P450 enzymes convert
also detoxify?
linear isoprenoid squalene into cholesterol
- also detoxify xenobiotics and pharmacological agents (including statins)
agents that inhibit CYP (cytochrome P450) cause what
increase in statin levels leading to toxic side effects
-clarithromycin, itraconozole, cyclosporine, citrus juices, grapefruit juice
agents that induce CYP
decrease levels of statin in plasma
-rifampicin, carbamazepine, and st john’s wort
elimination of cholesterol
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
