Cholesterol Metabolism Flashcards
Cholesterol is synthesized from ____ ___ in the cytosol or taken up from the diet. Cholesterol is a very ____ structure, who is rigidity plays an important role in regulating the fluidity of membranes.
Acetyl Coa
Insoluble
Cholesterol is the precursor of ___ ___, ___ hormones, and ___ _.
Bile salts
Steroid
Vitamin D
In the body cholesterol can be ___ or ____ to a fatty acid.
Free
Esterified
Cholesterol has one precursor: ___ ___, from the cytosol and is generated primarily from the citrate lyase reaction
Acetyl CoA
Four stages of cholesterol synthesis:
1. Three acetyl CoAs make ____ (6C)
2. Mevalonate is converted to ____ (5C)
3. Six isoprenes condense to form _____ (30 C)
4. Squalene is cyclized and converged to ____(27 C)
Mevalonate
Isoprene
Squalene
Cholesterol
The key regulatory enzyme in cholesterol synthesis:
Beta-hydroxy-beta-methylglutaryl CoA reductase (HMG CoA reductase)
Cholesterol synthesis occurs in the ____ and requires a lot of ____.
Cytosol
Energy
Cholesterol synthesis: first step:
3 acetyl CoAs condense to form ___ ___. Then ___ ___ ____ removes coenzyme A and reduces the aldehyde to an alcohol forming ____.
HMG-CoA
HMG CoA reductase
Mevalonate
HMG CoA reductase is an important drug target for managing ___ ___.
High cholesterol
Transcriptional regulation of HMG CoA reductase:
When cholesterol is abundant, the transcription factor sterile response element binding protein ( _____) is sequestered in intracellular membranes in complex with SREBP cleavage activating protein (______). When cholesterol levels drop, _____ cleaves the DNA binding domain of ____, which then translocate to the nucleus and regulates transcription of HMG CoA reductase
SREBP
SCAP
SCAP
SREBP
High ____ levels promote proteolysis and degradation of HMG CoA reductase
Sterol
In fasted conditions, HMG CoA reductase is phosphorylated and inactivated by ____. AMP-K is activated by ___ and ___.
AMP-K
AMP
sterols
Insulin promotes cholesterol synthesis by activating ____ that dephosphorylates HMG CoA reductase
Phosphatases
Three ____ are added to Mevalonate to form 3-phospho 5-pyrophosphomevalonate, which is dephosphorylated and decarboxylated to form 3-isopentenyl pyrophosphate which can then isomerize to dimethylallyl pyrophosphate.
Phosphates
Three isoprenes condense to form two ___ ____, which join together to form thirty carbon ____.
Farnesyl pyrophosphate
Squalene
Farnesyl pyrophosphate is a common precursor of ____, ____ (coenzyme Q), and ____.
Cholesterol
Ubiquinone
Dolichol
The thirty carbon Squalene is hydroxylated and cyclized to form ____. Subsequent reactions reduce the acyl chain and remove methyl groups to form the 27 carbon ____.
Ianosterol
Cholesterol
The liver can export cholesterol in the form of cholesterol esters in ___ particles into the blood, bile acids, and the lumen of the gut
VLDL
To be effective detergents that emulsify dietary fat, bile acids must be ____. Rate limiting step in bile acid synthesis is ____ of C7 of ____.
Amphipathic
Hydroxylation
Cholesterol
Bile salts act as detergents and make dietary fats ___ and accessible to ____.
Soluble
Lipase
Dietary fat and cholesterol are packaged as ___ ____ by intestinal epithelial cells. The ___ enter the lymphatic circulation first and then are transported to the blood.
Nascent chylomicrons
Chylomicrons
Cholesterol is transported into intestinal epithelial cells through the ___ ___ ___ -like-1 protein (NPC1L1). The cholesterol lowering drug ___ blocks cholesterol transport through NPC1L1.
Niemann Pick C1
Ezetimibe
In the blood, ____ particles transfer ApoCII to nascent ____ to make mature Chylomicrons. ApoCII activates ___ ___ (___).
HDL
chylomicrons
Lipoprotein lipase (LPL)
____ are the largest and least dense of the lipoprotein particles
Chylomicrons
