Cholesterol Flashcards
Dietary Sterols
plant sterols > phytosterols (_____ most common)
_____ (shrimp, crabs)
eggs (yolk)
_____ (egg nog, pecan pie, etc.)
sitosterol
seafood
holiday foods
USDA view on Cholesterol
2015 Report
Cholesterol Limit _____ from 2015 Dietary Guidelines. The advisory panel has decided to eliminate warnings about dietary cholesterol, According to the report, “cholesterol is not a nutrient of concern for _____.”
removed
overconsumption
Dietary Sterols: Normal Physiology REWATCH
In humans- Cholesterol cannot be broken down
into its _____ EVER
So we shuttle de novo synthesized and dietary cholesterol
BUT
Cholesterol is the precursor to _____, _____, _____- so we can’t live without it
component parts
hormones
bile
Vitamin D3
Intestinal Absorption of Cholesterol
Cholesterol absorption by intestinal cells (enterocytes) is a key _____ in sterol metabolism.
The less we absorb the more we need to synthesize- not a _____
regulatory point
bad thing
Intestinal Absorption of Cholesterol
More dietary cholesterol we take in; the more cholesterol delivered to liver; absorb 20-80%, the vast majority goes into making _____
excreted; but 95% of bile returns to the _____(lose very little bulk cholesterol in biliary excretion)
regulate, based on the level of the _____ (the less we absorb, the more we have to synthesize > much easier to control the _____ than to control the _____ of cholesterol)
bile liver enterocytes synthesis absorption
_____ protein family necessary to regulate cholesterol absorption
• _____ Trans-membrane domains
• Couple ATP hydrolysis to the transport of
excess or unwanted _____ or _____ from enterocyte back into gut lumen.
• Mutations in genes encoding these proteins results in _____
• Sitosterolemia –leads to accumulation of cholesterol and phytosterols in enterocytes and bloodstream- formation of _____.
adenosine triphosphate (ATP) binding cassette (ABC) protein
6
cholesterol
plant sterols
sitosterolemia
artherosclerotic plaque
Intestinal Absorption of Cholesterol
Transport out of the enterocyte into gut lumen is mediated by members of the ATP binding cassette protein family, _____ and _____
55% of intestinal pool enters blood through enterocytes by _____ or via _____
ABCG5
ABCG8
diffusion
Niemann-Pick C1-like 1 protein (NPC1L1)
Intestinal Absorption of Cholesterol
_____ takes chol from lumen of SI into the enterocyte
as cholesterol enters in intestine; NPC1L1 takes into enterocyte (repackages) and transports into the blood
these two transporters act in concert in order to maintain homeostasis
drug: _____; inhibits NPC1L1, inhibit chol uptake > lowering chol bc you’re not _____; decreasing dietary cholesterol > now forcing the liver to _____ the cholesterol (which is easier to regulate)
NPC1L1
ezetimibe
absorbing
synthesize
Cholesterol
• Cholesterol- a _____ nucleus consisting of _____ fused rings.
• It is _____ due to the OH group on the #3 carbon and a hydrocarbon chain on C#17.
• Sterols are the precursors to biologically active compounds including, _____, hormones and _____.
high levels of free cholesterol (crystallize out, which attracts _____ > formation of plaque)
steroid four amphipathic bile acids vitamin D
hydroxyapatite
Features and Stages of Cholesterol Synthesis
- Mostly in _____
- Synthesis Rxns occur in _____ and _____
- Primary intermediate is the _____ unit
- All 27 carbons are provided by _____ units
- _____-reducing equivalent
- _____-energy soucr
liver cytosol ER isoprene acetate NADPH ATP
Features and Stages of Cholesterol Synthesis
STAGE 1 - condensation of 3 acetate units to form _____.
STAGE 2 - polymerization of 6, 5-carbon isoprene units to form linear _____.
STAGE 3 - _____ of squalene to form sterol ring and ultimately cholesterol.
mevalonate
squalene
cyclization
Features and Stages of Cholesterol Synthesis
entire structure derived from _____; from cytosolic acetyl CoA (may need breakdown of glucose/protein to have chol synthesis > more likely to be synthesized during a _____ stage (regulated by insulin + glucagon)
acetate
“fed”
Stage 1 of Cholesterol Synthesis
reverse reaction for FA > reaction for _____ synthesis
ketone body synthesis is within the _____; chol biosynthesis is _____
source of acetyl-CoA > high _____, _____ inhibited > citrate leaves the mitochondria > gives you elevated _____ in the cytosol
ketone body synthesis mitochondria cytosol blood glucose pyruvate dehydrogenase acetyl CoA
Regulated Step of Biosynthesis-HMGCoA Reductase
_____- cholesterol lowering drugs
Competitive inhibitor of _____.
Lowers serum cholesterol by approx. _____.
Side-effects; liver
problems, muscle pain, etc.
HMGCoA Reductase = _____ (2 NADPH’S)
statin’s prevent the synthesis of _____; bind the active site and competitively inhibit
statins
HMG CoA Reductase
50%
regulating step
mevalonate
Stage 2 Cholesterol Synthesis
Stage 2
• Activated _____ polymerize to form _____
• The 30C squalene molecule is synthesized from 6 molecules of 5 C _____
• Addition of the _____ keeps the molecules water soluble and drives subsequent reactions
isoprene units
squalene
isopentyl pyrophosphates
phosphate groups