Biochemistry-test 4-cholesterol
On a low-cholesterol diet, the liver synthesizes about _____ mg cholesterol perday to replace ______ _____ and cholesterol lost from the __________ circulation into the feces.
800 bile salts, enterohepatic
Regulation by proteolytic degradation -high cholesterol levels induce proteolytic ________ of the HMG-CoA reductase.
degradation
Cholesterol is obtained from the ______ or synthesized by a pathway that occurs in most cell of the body. -Cholesterol absorption by ________ cells is a key regulatory point in human cholesterol metabolism. -In normal individuals, approximately ____% of the intestinal pool enters the blood through the ________ each day.
diet intestinal 55%, enterocyte (a cell of the intestinal lining)
A greater intake of ________ cholesterol suppresses the rate of hepatic cholesterol ________
dietary, synthesis
Cholesterol synthesis facts: -_________ pathway powered by the hydrolysis of high-energy ________(acetyl-CoA) and ____________(ATP) bonds.
endergonic thioester phosphoanhydride
Cholesterol is transported as cholesteryl _________ for delivery to tissues ________ cholesterol
ester, requiring
The bulk of synthesized cholesterol is secreted from the hepatocyte as: -cholesterol _________ -_______ cholesterol -_______ salts
esters biliary bile
SREBP is a transcription _______, which is an integral protein of the _________ reticulum (ER) and is bound to ________ protein in the ER membrane when cholesterol levels are _______
factor, endoplasmic, SCAP, high
When cholesterol levels drop, SREBP-SCAP complex is transported to the _______ apparatus. -Within the golgi, _________ cleavage releases the transcription factor domain (DNA-binding domain) of ________. THe activated transcription factor translocates to the ________, binds to _____, and activates transcription of the HMG-CoA reductase gene.
golgi proteolytic SREBP nucleus, SRE
Cholesterol esters are more __________ than the free cholesterol
hydrophobic
Cholesterol is present in the animal cell ________ only. The amount of cholesterol in an animal membrane regulates ________ of these membranes.
membrane fluidity
Regulation at the transcriptional level -The rate of synthesis of HMG-CoA reductase __________ RNA (mRNA) is controlled by a ________-regulatory element (SRE) sequence present in the __________ DNA. SRE _________ transcription of the HMG-CoA reductase gene.
messenger, sterol, nuclear, enhances
Cholesterol synthesis occurs in 4 stages -synthesis of ________ from acetyl CoA -Conversion of mevalonate to 2 __________ -Condensation of isoprene's to form _________ -Conversion of squalene to the ________ nucleus.
mevalonate isoprenes squalene steroid
Regulation by phosphorylation -Elevated glucagon levels increase __________ of the enzyme, thereby inactivating it -Insulin _________ the activity of the HMG-CoA reductase by activating _________, which dephosphorylates the reductase.
phosphorylation increases, phosphatase
The kinase that phosphorylates HMG-CoA reductase is the adenosine ___________ (AMP)-activated protein kinase (AMPK)
monophosphate
The structure of cholesterol suggests that its synthesis involves a _____-reaction pathway, and requires energy input and significant ______ power
multi, reducing
Stage 1-synthesis of mevalonate
...
approximately ___ of plasma cholesterol exists in the free, unesterified form. -The remaining 2/3 exists as cholesterol ______ in which a long-chain fatty acid (usually _______ acid) is attached by ester linkage to the hydroxy group at ____ of the A ring.
1/2 esters, linoleic, C3
In its "free" form, the cholesterol molecule contains: -_____ carbon atoms -hydroxyl group at ____ -a double bond between ___ and ___ -an ______-carbon hydrocarbon chain attached to carbon ___ in the D ring -a methyl group (carbon 19) attached to carbon ___ -a second methyl group (carbon 18) attached to carbon ____
27 C3 C5, C6 eight, 17 10 13
Diet ≈ ______ mg/day De novo (starting from beginning) synthesis in different tissues≈_______mg/day
300 1000
Acetyl CoA can be obtained from several sources: -The ___-________ of fatty acids -The oxidation of _________ amino acids, such as _______ and _______ -The oxidative decarboxylation of __________ in carbohydrate metabolism.
B-oxidation ketogenic, leucine, lysine pyruvate
Cholesterol cannot be degraded to ____ and _____ in humans. Sterol nucleus is eliminated through bile _____ and bile _____ and excreted in the ______
CO₂, H₂O, acids, salts, feces
The reducing equivalents are provided by ______
NADPH
The reducing power for cholesterol synthesis is supplied by _________, which is produced in the reactions catalyzed by ________-6-________ dehydrogenase and 6-____________ dehydrogenase of the _________ _______ pathway.
NADPH, glucose-6-phosphate, phosphogluconate, pentose phosphate
When cytoplasmic cholesterol levels rise, cholesterol binds to and inactivates _______-_______ complex, prevents its translocation to the golgi and activation, which decreases __________of the reductase gene and new protein synthesis.
SREBP-SCAP transcription
All the carbon atoms of cholesterol are provided by ________ groups
acetyl
All 27 carbons are derived from one precursor, ______ _____
acetyl CoA
Building blocks for cholesterol synthesis -Cholesterol synthesis is driven by the hydrolysis of _______-CoA and ______
acetyl, ATP
Cholesterol esters -Cholesterol ester production in the liver is catalyzed by _____ CoA-cholesterol _____ transferase (ACAT) -ACAT catalyzes the transfer of a fatty acid from _________ A to the _________ group on carbon 3 of cholesterol
acyl, acyl coenzyme, hydroxyl
Cholesterol is an _________ compound whose basic structure includes the sterol nucleus containing four fused rings.
alicyclic
Cholesterol is synthesized by ____ tissues smallest to biggest: -other tissues -________ organs -_________ -________
all reproductive intestines liver
VLDL(very low density lipoprotein) is secreted from the hepatocyte into the _______ and transports the cholesterol esters to the tissues that require greater amounts of cholesterol than they can ________
blood, synthesize
The liver packages some of the esterified cholesterol into the hollow ________ of lipoproteins, primarily _______
core, VLDL
The adrenal _______ and the _______ also synthesize cholesterol in significant amounts and use it as a precursor for _______ hormone synthesis.
cortex, gonads, steroid
The steroid hormones, derived from cholesterol, include: -the adrenal ________ hormones (e.g. cortisol, aldosterone, and the adrenal sex steroids dehydroepiandrosterone, DHEA, and androstenedione) and -the ________ hormones (e.g., the ovarian and testicular sex steroids, such as testosterone and estrogen)
cortical gonadal
The synthesis occurs in the ________ and on the __________ reticulum
cytosol endoplasmic
Bile acids are synthesized from cholesterol in the ________ in a multistep pathway in which ____ groups are inserted at specific positions on the sterol nucleus (_________ of the sterol nucleus). _________ side chain is cleaved
liver, OH, hydroxylation, hydrocarbon
The most active producers of cholesterol are the cells of the ________ (hepatocytes) and _______
liver, intestin
Thus, cholesterol synthesis decreases when ATP levels are _______ and increases when ATP levels are _____, similar to what occurs with fatty acid synthesis.
low, high
Cholesterol synthesis is regulated through HMG-CoA ___________-in multiple ways and many levels 1) gene _________ and new ________ synthesis 2) protein (enzyme) degradation by _________ 3) _________ modification (phosphorylation by _____-dependent kinase, AMPK) 4) _________ regulation 5) _________ inhibition-used by multiple pharmacotherapies
reductase 1) transcription, protein 2) proteolysis 3) covalent, AMP 4) allosteric 5) competitive
Bile ______ are the only route for cholesterol ________ from the body
salts, excretion
_________ are competitive inhibitors of HMG-CoA reductase, thereby decrease cholesterol synthesis. Statins are used to treat ___________. They resemble ________
statins, hypercholesterolemia, mevalonate
Cholesterol consists of the _______ nucleus (____ hydrocarbon rings) and a hydrocarbon ________ chain
steroid, 4, branched
The membrane domains of HMG-CoA reductase contain ______ sensing sites. Rising levels of cholesterol and _____ salts in cells cause a change in the __________ state of the HMG-CoA reductase, rendering the enzyme more susceptible to ________, thus decreasing the enzyme's activity in these cells.
sterol bile, oligomerization (joining monomers) proteolysis
The residual cholesterol esters not used in these ways are _______ in the liver for later us
stores
Cholesterol esters serve as the _______ form of cholesterol. They are packaged into _________ and delivered to tissues that require cholesterol _______ -Takes place in the _______ in hepatocytes.
transport, lipoproteins, import, liver
Precursors of cholesterol are converted to: -_______ -______, and -in the skin, to _________, the active form of vitamin D
ubiquinone dolichol cholecalciferol
As a major component of blood lipoproteins, cholesterol can appear: -in its free, ________ form in the _______ shell of these macromolecules, and as cholesterol _______ in the lipoprotein _______
unesterified, outer esters, core
Cholesterol, which is absolutely insoluble in ______, serves as: -a stabilizing component of cell ________ -a precursor of the _____ salts -a precursor of steroid _______, and -a precursor for vitamin _____
water membrane bile hormones D
