Liver Biochemistry Flashcards
What protein made by the liver is a inflammatory marker and a marker for heart disease?
C reactive protein
What liver cells protect against viruses and tumors?
Pit cells (Lymphocytes)
What comes together to form IPP?
3 acetyl CoA’s
What are the sources of acetyl CoA?
- oxidative decarboxylation of pyruvate
- Beta oxidation of fatty acids
- Breakdown of amino acids
Acetyl CoA is transported into the cytoplasm via what?
Citrate shuttle
How many units of IPP form the tetracyclic (4 ring) sterane backbone of most steroids?
6
What carbon on cholesterol has a hydroxyl group?
C3
Where is the double bond on cholesterol?
Between C5 and C6
The liver packages cholesterol into what?
VLDL molecules
Enzyme from Acetyl CoA –> Acetoacetyl CoA
Acetyl CoA acetyltransferase
Enzyme for Acetoacetyl CoA –> HMG CoA
HMG CoA synthase
Enzyme for HMG CoA –> Mevalonate
HMG CoA reductase
What step is the rate limiting step in cholesterol biosynthesis?
HMG CoA –> Mevalonate using HMG CoA reductase
Name all the intermediates in cholesterol biosynthesis in order
Acetyl CoA –>Acetoacetyl CoA –> HMG CoA –> Mevalonate –> IPP –> Squalene –> Lanosterol –> Cholesterol
What 2 things accelerate or promote the reaction of HMG CoA to Mevalonate?
Insulin and thyroxine
What things inhibit or slow down the reaction of HMG CoA to Mevalonate?
Glucagon, Sterols, high AMP, Vitamin E, and statins
What inhibits conversion of Lanosterol to cholesterol?
Antifungal agents
What things are formed from side reactions from intermediates of cholesterol synthesis?
Ubiquitous and Heme A (in cytochromes)
Long term statin use for cholesterol regulation will inhibit the formation of what?
Ubiquinone which will mess up TCA cycle
Local centers for signal transduction processes and sites for abnormal processing of proteins in neurodegenerative disorders?
Lipid rafts
Where are the ubiquitination sites on HMG CoA reductase?
Lysine 89 and Lysine 248
What membrane is HMG reductase on?
ER
The catalytic domain of HMG CoA reductase faces what?
The cytosol
HMG CoA reductase is directly inhibited by what?
Free Fatty acids, Bile Acids, and oxysterols
These are pharmacological molecules that are competitive inhibitors and sit in the active site of HMG CoA reductase
Statins
Referring to covalent modifications, HMG CoA reductase is Active in what form?
Dephosphorylated
Low energy state does what to HMG CoA reductase?
Causes phosphorylation thus inactivation
Translation of HMG CoA reductase is reduced by what?
Gamma-tocotrienol (vitamin E family) and oxylanosterols
In the presence of high cholesterol, HMG CoA interacts with INSIG which causes what?
Polyubiquitination of HMG CoA reductase
Polyubiquitination of HMG CoA reductase leads to removal from the ER and degradation by what?
26S protea some
While synthesized cholesterol is packaged into VLDLs, dietary cholesterol is delivered to the liver via what?
Chylomicron remnants
In the synthesis of Bile Acids, cholesterol is converted to ________ by the enzyme ________.
7-alpha- hydroxycholesterol; 7-alpha-hydroxylase
Name the intermediates in bile acid synthesis in order.
Cholesterol –> 7-alpha-hydroxycholesterol –> chenocholic acid –> cholinergic acid