Lecture 35 Flashcards
(17 cards)
The 27 Carbons of Cholesterol are all derived from ____
ACETATE
The C-3 _____ group can be esterified.
HYDROXYL
The C-17 side chain can be modified with a ______carbon tail.
HYDROcarbon tail
Cholesterol is mostly reabsorbed in the intestines, but it can be converted into ____ salts and acids. It is stored in the ___ ______, secreted into the intestines to help with emulsification of fatty acids and absorption of liposoluble vitamins (A, D, E, K) and a small % (about 5%) can be excreted in the ____. We don’t actually need cholesterol in our diets bc it is produced in the ____ and intestines.
BILE Gall Bladder FECES Liver
The major form cholesterol is transported throughout the body in is the ______ form. It is ______ at C-3 with a fatty acid and packaged into _______.
ESTERIFIED ESTERIFIED Lipoprotein
In the first part of Cholesterol synth, 2 acetyl CoA molecules are converted to _____CoA.
HMG CoA
The rate limiting step of Cholesterol Synthesis is the conversion of HMG CoA to _____ acid via the enzyme _____ reductase (requires NADPH.) This occurs in the _____ reticulum of hepatocytes.
MEVALONIC acid HMG CoA reductase (requires NADPH.) ENDOPLASMIC reticulum.
How many ATP and NADPH are required to synthesize Cholesterol?
18 ATP and 14 NADPH
When intracellular Cholesterol levels are high, transcription of cholesterol synthesis enzymes is ______. The transcription factor responsible for this regulation is ____.
INHIBITED SREBP (Sterol Response Element Binding Protein)
When ER sterols are low, ____-SREBP moves to the golgi where two ____ cleave ____ from SREBP, making it soluble so it can translocate to the nucleus (remember SREBP is a TRANSCRIPTION factor)/
SCAP-SREBP PROTEASES SCAP
Regulation of Cholesterol synth can also be mediated by degradation of HMG CoA Reductase (HMGR.) When ER cholesterol levels are low, the HMGR is properly ______. When levels are high, HMGR is mis_____ and degraded.
Low cholesterol levels –> HMGR is properly FOLDED. High levels –> MISFOLDED and degraded.
When HMGR is ______, it is inactive. This process is mediated by AMP-activated Kinase, which should make sense bc cells are not going to synthesize cholesterol, which requires large amounts of energy, when ATP is low and AMP is high.
PHOSPHORYLATED
Statins act as ______ inhibitors of HMGR by mimicking Melvadyl-CoA
COMPETITIVE inhibitors
__-____-______ is the enzyme involved in the rate limiting step of bile acid synthesis from Cholesterol (cholesterol degradation and elimination pathway) . It is inhibited by ____ acid and stimulated by _____ in rodents (but not humans). Bile salts and acids are sequestered in the intestines by binding ____, and are thus excreted.
7-alpha-hydroxylase
CHOLIC
CHOLESTEROL
Fiber
How does the amount of cholesterol in membranes change as you move from the RER to the Golgi to Secretory vesicles to the Plasma membrane?
It increases as you move from the former to the latter.
How does Ezetimibe help lower cholesterol? Where does it act, and what does this mean for side effects?
It inhibits cholesterol absorption. It acts at the small intestine brush border, so it doesn’t enter the blood stream –> no side effects.
How does Vytorin act, and how does this affect statin side effects?
It is a combination of ezetimibe and simvastatin, so it acts by blocking absorption of cholesterol at the small intestine brush border, and it copetitively inhibits HMG CoA reductase. Bc it’s a combo, it can use a lowe dose of statin, reducing the side effects.
