Liver Biochemistry Flashcards
what are the two ways into the liver? (what are each rich in?)
way out?
75% through the portal vein (from the GI) –> nutrient rich
25% from the hepatic artery (systemically) –> oxygen rich
Hepatic Vein (three veins that meet up with the IVC)
Main cell type of the liver?
What’s between the lobules of the liver?
What are present between hepatocytes and sinusoids?what’s interesting to know about these?
what’s within the lobules?
hepatocyte
sinusoids (close contact between blood and liver cells)
endothelial cells. very loosely packed to facilitate exchange of material from blood to hepatocytes and the other way around too
Bile canniliculi!
What do endothelial cells have that allow for exchange of material from the liver to blood and vice versa?
pores/fenestrations in the plasma membrane!
Kupffer cells?
what do they have inside?
macrophages of the liver.. their function is to protect the liver from microbes!
they have lots of lysosomes to engulf and destroy them.
What are Hepatic Stellate Cells?
important factoid about hepatic stellate cells?
storage site for Vitamin A and other lipids.
if you’ve touched a liver it’s pretty squishy, the stellate cells contribute to the squishyness
Pit cells (lymphocytes)?
NK cells pretty much, protecting the liver against virus and tumor cells
Cholangiocytes?
Line bile duct, control bile flow rate and bile pH
What is the biggest function fo the liver?
what are the next biggest thing?
what does the liver do to toxins?
primary receiving, distribution, and recycling… any process in the body is presented to the liver. so it’s the gateway to distributing stuff and recycling.
Glucostasis (maintains glucose levels under fed, fasting, and starving state) –> remember we did most of our carbohydrate metabolism in the liver too!
Waste Management –> inactivation, detox, and biotransformation for secretion
What is the unique circulation of the liver?
what’s the blood pressure in the liver like? why is this important?
it gets all the blood from the enteric circulation via the portal vein and the periphery from the hepatic artery!
low, so it maximizes the exchange occurring!
What structural features of the liver are important to know? (3) (2 of them are regarding endothelial cells)
why are these important!
lack of a basement membrane and absence of tight junctions between hepatocytes and endothelial cells!
Gaps between endothelial cells
Fenestrations in endothelial cells
INCREASE A GREATER access and increased contact between liver and blood
What are Isoprenoids?
what do these do?
important one to know?
Acetyl Coa –> generates IPP, which is the backbone to many compounds.
IPP forms a bunch of compounds like steroids, lipid soluble vitamins, and ubiquinone, all of which are a broad category named isoprenoids
create a bunch of stuff
the important one to know is ubiquinone as well, but they also produce steroids, and lipid soluble vitamins.
Where do we get our acetyl coa
how do we get it? (3 ways)
where does it go once it’s made?
generated in the mitochondria from breakdown of pyruvate, or beta oxidation of fatty acids, or breaking down amino acids.
it’s then sent into the cytoplasm via the citrate shuttle!
What generates the sterane ring?
what is this common for?
6 units of IPP (from acetyl CoA) form the tetracyclic (4-ring) sterane ring
backbone of most steroids
What is the structure of cholesterol?
where’s the hydroxyl group located
it’s called an “allicyclic compound… hydrocarbon chain + sterane ring”
OH in the 3rd Carbon of the sterane ring.
Why is cholesterol so important?
component of plasma membranes
and
major precursor of bile acids, bile salts, vitamin d, steroid hormones.
in the biosynthesis to cholesterol, what’s important to know about dietary intake?
hint: counterintuitive
if you’re trying to lose weight so you ingest less, so your body makes more
Equation for cholesterol?
18 AcetylCoA + 18 ATP + 16NADPH + 16H + 4O2 –> Cholesterol
What is phase 1 of of cholesterol synthesis?
Acetyl CoA –> IPP
2 Acetyl CoA –> Acetoacetyl CoA
a third Acetyl coA comes in to form HMG CoA (by HMG CoA synthase)
NADPH comes in to form Mevalonate (HMG CoA reductase)
add 3 ATP and you form IPP
What’s the rate limiting step of cholesterol synthesis?
what is this also an important target for?
HMG CoA reductase
statins
if you are taking statins, what are you inhibiting?
statins inhibit HMG CoA reductase, which makes IPP… IPP makes all isoprenoids for cholesterol metabolism, but also lipid soluble vitamins ADEK and ubiquinone (which is for energy metabolism), so people are super tired all the time.
What is Phase 2 of cholesterol synthesis?
start with 6 IPP –> Squalene –> Lanosterol (here the cycling occurs)–> isomerizes to cholesterol
What inhibits lanosterol to cholesterol?
what are these used for usually?
what happens if you use them for long periods of time and at high doses?
(azoles) anti fungal drugs
they’re supposed to inhibit the fungal form, but at prolonged use and high concentration they can inhibit mammalian cholesterol
What kind of protein is HMG CoA reductase?
where does statins bind to?
located in the ER but kind of is an integral membrane weaving in and out.
the catalytic domain in the Cytosol!
What are Statins?
cholesterol lowering drugs
competitive inhibitors of HMG CoA reductase
Km for HMG CoA is 4 microMolar, Ki is 5-45 nM (1000x higher!!)
