• Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
Front

How to study your flashcards.

Right/Left arrow keys: Navigate between flashcards.right arrow keyleft arrow key

Up/Down arrow keys: Flip the card between the front and back.down keyup key

H key: Show hint (3rd side).h key

image

PLAY BUTTON

image

PLAY BUTTON

image

Progress

1/47

Click to flip

47 Cards in this Set

  • Front
  • Back
What are the functions of cholesterol?
-Inserts in membranes
-Precursor of bile salts
-Precursor of steroids
-Precursor of vitamin D
Where does the bulk of De Novo cholesterol synthesis occur?
LIVER
How is cholesterol leaving the liver?
-Component of HDL's
-Component of VLDL's
-Free Cholesterol as bile salts and acids
Where do the carbons used for cholesterol synthesis arise?
Acetate, NADPH supplies e-'s
Where does cholesterol synthesis occur in the hepatocyte?
Cytosol and endoplasmic reticulum
Cholesterol synthesis starts the exact same way that ketone synthesis does with the exception of what?
It is occuring in the cytosol of the cell and not the matrix. (2) AcCoA are combined to form Acetoacetyl CoA and then HMG-CoA but in the cytosol. By the enzymes Thiolase, and HMG CoA synthase.
What is the product of HMG-CoA via the enzyme HMG-CoA reductase in cholesterol synthesis?
Hydroxymethyglutaryl CoA ("HMG-CoA")
What is important about the enzyme HMG-CoA reductase?
It is the rate limiting enzyme for cholesterol synthesis and is only found in the liver.
What inhibits the rate limiting enzyme HMG-CoA reductase?
Cholesterol
Whats important to note about the steps from Mevalonic acid in cholesterol synthesis to squalene?
There are many steps, intermediates are phosphorylated, ATP is used to the tune of 7 ~P's, and 1 NADH is consumed (worth 3 ATP)
How many NADPH's are used in the conversion of HMG-CoA to Mevalonic acid via HMG-CoA reductase?
2 NADPH are used, and (1) CoA is released
What is notable about the conversion of Squalene, a cholesterol synthesis intermediate, to Lanosterol?
(1) O2 and (1) NADPH are required, yielding (1) NADP and (1) H2O. Also, the structures from this point on are very hydrophobic and are bound to a carrier protein
What is the immediate precursor to cholesterol?
Lanosterol, there are no remarkable steps Tim would like us to know about this step.
What are Lovastatin & Metastatin?
Anti-Cholesterol (hypolipidemic) drugs that inhibit HMG-CoA reductase (the rate limiting enzyme of cholesterol synthesis)
Can cholesterol be used for energy? And what is its fate?
No, it cannot.

It is used in bile acids, which can be excreted in the feces, or free cholesterol in bile that remains in the feces.

-Also, cholesterol can be used to make steroid hormones.
How many classes of steroid hormones are there and what are they?
There are 5:
-Glucocorticoids (Cortisol)
-Mineralcorticoids (Aldosterone)
-Androgens (Testosterone)
-Estrogens (Estradiol)
-Progestins (Progesterone)
What determines the specific hormone a tissue produces?
What enzyme it contains, based on gene expression
Do both hormones and steroid hormones circulate in the blood freely?
Hormones circulate freely in the blood,

Steroid hormones are hydrophobic and are transported in the blood bound to: Albumin, Transcortin (in case of cortisol), and Sex Hormone Binding Protein for the sex hormones.
What is the rate limiting enzyme for steroid hormone synthesis?
Desmolase
What is desmolase?
It is the rate limiting enzyme for synthesis of all hormones
What is the function of desmolase?
Converts cholesterol to pregnenolone using (1) NADPH and (1) O2.
What are the many fates of Pregnenolone?
Corticosterone->Aldosterone

Progesterone--->Cortisol

Testosterone--->Estradiol
Can steroids be stored?
No, steroids are lipid soluble so they would pass through lipid membranes. They are made on-demand and automatically leave endocrine cells.
What is the "Demand" that is a regulatory polypeptide hormone responsible for stimulating desmolase activity in the endocrine cell?
ACTH in the example he gave us, binds the receptor stimulating a 2nd messenger which stimulates Desmolase activity which enzyme converts cholesterol to pregnenolone
How do steroids alter cell behavior?
The alter cell gene expression
What is the total activity of a protein?
Its specific activity multiplied by the amount or # or enzyme molecules
In addition to becoming steroids, what else can FA's become?
Intercellular signals called Eicosanoids (which contain 20 carbons)
What are eicosanoids?
20 carbon unit molecules derived from FA's:
-Prostaglandins
-Thromboxanes
-Leukotrienes
Why aren't Eicosanoids hormones?
They have a short life-expectancy and almost no time to circulate in blood to effect distant tissues/cells.
What are Eicosanoids also known as?
Paracrines. Compounds which aren't steroids or hormones but alter the behavior of neighboring cells. Paracrines are very potents and produced varied responses throughout the body.
What is an example of an eicosanoid?
Arachidonic acid
What is the precursor of arachidonic acid?
Linoleic acid, an essential FA. We also get dietary arachidonic acid.
What is the source of arachidonate for prostaglandin synthesis?
Phospholipids present in our diet.
Phospholipid in cell membranes is converted to arachidonic acid via which process?
Phospholipase A2 cleaves phospholipids yielding Arachidonic acid and a lysophospholipid
What inhibits the activity of Phospholipase A2?
Corticosteroids (cortisol, cortisone)
What is the fate of arachidonic acid?
Converted to 5-HPETE via 5-lipoxygenase

Converted to Prostaglandin G2 (PGG2) via cyclo-oxygenase found in microsomes
What is the fate of 5-HPETE from Arachidonic acid?
Becomes Leukotriene A4 and other Leukotrienes
What is the fate of Prostaglandin G2 (PGG2)?
Converted via peroxidase to PGH2, which can then become:

Thromboxane A2 via thromboxane synth.

PGI2 (prostacyclin)

PGE2--->PGF2alpha
What are leukotrienes?
Factors that respond to tissue damage.
What is the action of leukotrienes?
Smooth muscle contract
Bronchoconstriction
Slow anaphalaxis
Lysosomal release
White BC adhesion
What is Thromboxane A2 and its effects?
Mostly made by platelets and promote aggregation and vasoconstriction at wound sites.
What is PGE2 and its function?
Most tissues synthesize it but especially the kidney, causes vasodilation and is also used to promote labor.
What is PGF2 and its function?
Made in most tissues. A vasoconstrictor which stimulates smooth muscle and uterine contraction.
What is PGI2 and its function?
Prostacyclin; Primarily made by endothelial cells and causes vasodilation and inhibits platelet aggregation.
Are cyclo-oxygenase and peroxidase two separate enzymes?
No, they are two domains of the same protein complex called prostaglandin synthase
What inhibits cyclo-oxygenase activity?
Aspirin, other NSAIDS, Indomethacin, phenylbutazone. These factors provide their anti-inflammatory effects via this mechanism.
What does Dipyridamole do?
Inhibits Thromboxane synthase, inhibiting thromboxane production without affecting PG's (prostaglandins)