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