Liver Biochemistry Flashcards
(42 cards)
What supplies most of the blood to the liver?
protal vein
What do hepatic stellate cells do?
store lipids and vitamin A
What are some functions of the liver?
- recycling center
- lipid biosynth and management
- make Albumin and IgG
- N metabolism , Urea cycle
- waste management: seonobiotic reactions
- bilirubin metabolism
- fuel management
What characteristics of the liver allow for greater access and increased contact b.w theliver and blood?
- no basement membrane between endothelial cells and hepatocytes
- gaps b/w endothelial cells
- fenestrations in endothelial cells
- low portal blood pressure
What are hepatocytes like?
well developed pasma membrane and ER, lots of mitochondria, lots of lysosomes
What is the building block of all isoprenoids and what is used to make it?
IPP
-3 acetyl coA’s go into it
What are some sources of Acetyl CoA?
generated in mitochondria from:
- oxidative decarboxylation of pyruvate
- B ox of fatty acids
- breakdown of aa’s
how is Acetyl CoA transported into the cytoplasm?
via citrate shuttle
What is the backbone of most steroid?
the tetracyclic sterane ring
-made up of six IPP’s
What is one important characteristic about the structure of cholesterol?
the OH group at C3
What does cholesterol make?
Bile acids and salts
Vit D
Steroid hormones
How many ATP go into making one Cholesterol?
18
that’s a lot of energy
What are the 2 phases of Cholesterol synthesis?
- Generation of IPP from Acetyl CoA
- Generation of cholesterol from IPP
What does HMG CoA synthase do?
Acetoacetyl CoA —> HMG CoA
*uses an Acetyl CoA here
What do HMG CoA reductase do?
HMG CoA—–> Mevalonate
*uses 2 NADPH’s… and a CoA pops off in this step
What is the rate limiting step?
The one involving HMG CoA reductase
- HMG CoA—–> Mevalonate
What enhances the rate limiting step of cholesterol synthesis?
Insulin and thyroxine
What inhibits the rate limiting step?
Glucagon, sterols, high AMP, Vit E, and Statins
What are some compounds derived from intermediates in cholesterol synthesis?
Quinol from ubiquinone
Heme A
List the intermediates in order in cholesterol synthesis.
Acetyl CoA, Acetoacetyl CoA, HMG CoA, Mevalonate, IPP, Squalene, Lanosterol, cholesterol
What happens to cholesterol after it is made?
gets packaged into VLDL and released into circulation
How is Cholesterol cynthesis mainly regulated?
HMG CoA reductase
- the rate limiting enzyme
- can happen by direct inhibition, covalent mod, transcriptional control, translational control, or post-translational control- protein turnover
How does direct inhibition go?
- HMG CoA reductase inihibited by Free FA’s , buile acids, and oxysterols
- also inibited by statins
What are statins,
competitive inihibitors of HMG CoA reductase
- compete w. HMG coA for binding to active site
- statin lacks the Methyl group*
- these are cholesterol lowering drugs
- bind more tightly to the active site