Ch 25 - Lipid Transport And Storage Flashcards by AFD Alvarez

Fat absorbed from the diet and lipids synthesized by the _________ and adipose tissue must be transported between the various tissues and organs for utilization and storage.

liver

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Since lipids are insoluble in water, the problem of how to transport them in the aqueous blood plasma is solved by associating nonpolar lipids (triacylglycerol and cholesteryl esters) with amphipathic lipids (phospholipids and cholesterol) and proteins to make ___________________.

water-miscible lipoproteins

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In a meal-eating omnivore such as the human, excess calories are ingested in the _________ phase of the feeding cycle, followed by a period of negative caloric balance when the organism draws upon its carbohydrate and fat stores.

anabolic

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Lipoproteins mediate this cycle by transporting lipids from the intestines as ______________ —and from the liver as __________________—to most tissues for oxidation and to adipose tissue for storage.

chylomicrons

very low density lipoproteins (VLDL)

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Lipid is mobilized from adipose tissue as free fatty acids (FFAs) bound to serum _______________.

albumin

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Abnormalities of lipoprotein metabolism cause various hypo- or hyperli-poproteinemias. The most common of these is in _____________, where insulin deficiency causes excessive mobilization of FFA and underutilization of chylomicrons and VLDL, leading to ___________________.

diabetes mellitus

hypertriacylglycerolemia

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Most other pathologic conditions affecting lipid transport are due primarily to inherited defects, some of which cause _________________ and premature ______________.

hypercholesterolemia

atherosclerosis

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___________—particularly ______________ —is a risk factor for increased mor-tality, hypertension, type 2 diabetes mellitus, hyperlipidemia, hyperglycemia, and various endocrine dysfunctions.

Obesity

abdominal obesity

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Lipids are transported in the plasma as _____________.

Lipoproteins

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Plasma lipids consist of triacylglycerols (____%), phospholip-ids (____%), cholesterol (___%), and cholesteryl esters (____%) and a much smaller fraction of unesterified long-chain fatty acids (free fatty acids or FFA) (____%).

16%
30%
14%
36%
4%

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The _________ is metabolically the most active of the plasma lipids

FFA

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Since fat is less dense than water, the density of a lipoprotein _____________ as the proportion of lipid to protein __________.

Decreases

Increases

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Derived from intestinal absorption of triacylglycerol and other lipids.

Chylomicrons

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Derived from the liver for the export of triacylglycerol.

VLDL

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Representing a final stage in the catabolism of VLDL.

LDL

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Involved in cholesterol transport and also in VLDL and chylomicron metabolism.

HDL

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____________ is the predominant lipid in chylomicrons and VLDL.

Triacylglycerol

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Cholesterol and phospholipid are the predominant lipids in ______ and ______ respectively.

LDL and HDL

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Lipoproteins may also be classified according to their electrophoretic properties into ____ (HDL), ____- (LDL), and ______ (VLDL)-lipoproteins.

Alpha

Beta

Pre-beta

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___________ consists of nonpolar core and a single surface layer of ampiphatic lipids.

Lipoproteins

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The _____________ consists of mainly triacylglycerol and cholesteryl ester and is surrounded by a single surface layer of amphipathic phospholipid and cholesterol molecules.

nonpolar lipid core

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The protein moiety of a lipoprotein is known as an ___________________, constituting nearly 70% of some HDL and as little as 1% of chylomicrons.

apolipoprotein or apoprotein

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Some apolipoproteins are integral and cannot be removed (eg, __________), whereas others are bound to the surface and are free to transfer to other lipoproteins, eg, ___________).

apo B

apos C and E

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The major apolipoproteins of HDL (α-lipoprotein) are ________.

apoAs

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The main apolipoprotein of LDL (β-lipoprotein) is _________, which is found also in VLDL.

apo B (B-100)

Chylomicrons contain a truncated form of apo B (B-48) that is synthesized in the _________, while B-100 is synthesized in the ___________.

Intestine liver

____________ is one of the longest single polypeptide chains known, having 4536 amino acids and a molecular mass of 550,000 Da.

Apo B-100

___________ (48% of B-100) is formed after transcription of the apo B-100 gene by the introduction of a stop signal into the mRNA transcript by an RNA editing enzyme.

Apo B-48

__________, _________, and _______ are smaller polypeptides (molecular mass 7000-9000 Da) freely transferable between several different lipoproteins.

Apos C-I, C-II, and C-III

_________, found in VLDL, HDL, chylomicrons, and chylomicron remnants, is also freely transferable; it accounts for 5% to 10% of total VLDL apolipoproteins in normal subjects.

Apo E

Apolipoproteins carry out several roles: they can form part of the structure of the lipoprotein, for example ________.

Apo B

They are enzyme cofactors, for example: _____ for lipoprotein lipase _____ for lecithin:cholesterol acyltransferase or enzyme inhibitors, for example: __________ and _________ for lipoprotein lipase __________for cholesteryl ester transfer protein

CII A-I Apo A-II and Apo C-III Apo C-I

They act as ________ for interaction with lipoprotein receptors in tissues: ________ and ________ for the LDL receptor ________ for the LDL-receptor-related protein-1 (LRP-1) which has been identified as the remnant receptor ________ for the HDL receptor.

Ligands Apo B-100 and Apo-E Apo E Apo A-I

_____________ is believed to be an important factor in human neurodegenerative disorders.

apo D

The ____________ also termed _____________ arise in the plasma from the breakdown of triacylglycerol in adipose tissue or as a result of the action of lipoprotein lipase on the plasma triacylglycerols.

FFAs (also termed nonesterified fatty acids [NEFAs] or unesterified fatty acids)

They are found in combination with __________, a very effective solubilizer, in concentrations varying between 0.1 and 2.0 meq/mL of plasma.

albumin

Levels are low in the fully fed condition and rise to __________ meq/mL in the starved state

0.7 to 0.8

In uncontrolled diabetes mellitus, the level may rise to as much as ___ meq/mL.

FFAs are removed from the blood extremely rapidly and oxidized (fulfilling _________% of energy requirements in starvation) or esterified to form triacylglycerol in the tissues.

25%-50%

In starvation, esterified lipids from the circulation or in the tissues are oxidized as well, particularly in ___________ and ___________, where considerable stores of lipid are to be found.

heart and skeletal muscle cells

True or False: The FFA uptake by tissues is related directly to the plasmaFFA concentration, which in turn is determined by the rate of lipolysis in adipose tissue.

True

After dissociation of the fatty acidalbumin complex at the plasma membrane, fatty acids bind to a ___________ that acts as a transmembrane cotransporter with Na+.

membrane fatty acid transport protein

On entering the cytosol, FFAs are bound by intracellular ______________. The role of these proteins in intracellular transport is thought to be similar to that of serum albumin in extracellular transport of long-chain fatty acids.

fatty-acid-binding proteins

TRIACYLGLYCEROL IS TRANSPORTED FROM THE ____________ IN CHYLOMICRONS & FROM THE _______ IN VERY LOW DENSITY LIPOPROTEINS

INTESTINES | LIVER

By definition, chylomicrons are found in _______ formed only by the lymphatic system draining the intestine.

chyle

They are responsible for the transport of all dietary lipids into the circulation.

Chylomicrons

Small quantities of VLDL are also to be found in chyle; however, most VLDL in the plasma are of _____________. They are the vehicles of transport of triacylglycerol from the liver to the extrahepatic tissues.

hepatic origin

There are striking similarities in the mechanisms of formation of chylomicrons by intestinal cells and of VLDL by hepatic parenchymal cells perhaps because—apart from the mammary gland—the _____________ and ____________ are the only tissues from which particulate lipid is secreted.

intestine and liver

Newly secreted or “nascent” chylomicrons and VLDL contain only a small amount of ________________, and the full comple ment is acquired from HDL in the circulation.

apolipoproteins C and E

_________, however, is an integral part of the lipopro-tein particles, it is incorporated into the particles during their assembly inside the cells and is essential for chylomicron and VLDL formation.

Apo B

In ________________ (a rare disease) lipoproteins containing apo B are not formed and lipid droplets accumulate in the intestine and liver.

abetalipoproteinemia

CHYLOMICRONS & VERY LOW DENSITY LIPOPROTEINS ARE RAPIDLY _____________.

CATABOLIZED

The clearance of chylomicrons from the blood is rapid, the half-time of disappearance being under _______ in humans.

1 hour

Fatty acids originating from chylomicron triacylglycerol are delivered mainly to adipose tissue, heart, and muscle (80%), while ~20% goes to the ________.

liver

However, the liver does not metabolize native ____________ and ________ significantly; thus, the fatty acids in the liver must be secondary to their metabolism in extrahepatic tissues.

chylomicrons or VLDL

Triacylglycerols of Chylomicrons & VLDL Are Hydrolyzed by _________________ to Form remnant Lipoproteins

Lipoprotein Lipase

________________ is located on the walls of blood capillaries, anchored to the endothelium by negatively charged proteoglycan chains of heparan sulfate. It has been found in heart, adipose tissue, spleen, lung, renal medulla, aorta, diaphragm, and lactating mammary gland, although it is not active in ___________.

Lipoprotein lipase | adult liver

It is not normally found in blood; however, following injection of __________, lipoprotein lipase is released from its heparan sulfate binding sites into the circulation.

heparin

______________ is bound to the sinusoidal surface of liver cells and is also released by heparin. This enzyme, however, does not react readily with chylomicrons or VLDL but is involved in chylomicron remnant and HDL metabolism.

Hepatic lipase

Both _____________ and ___________ are required as cofactors for lipoprotein lipase activity, while ____________ act as inhibitors.

phospholipids and apo C-II apo A-II and apo C-III

_______________ takes place while the lipoproteins are attached to the enzyme on the endothelium.

Hydrolysis

Triacylglycerol is hydrolyzed progressively through a diacylglycerol to a ________________ and finally to FFA plus ____________.

Monoacylglycerol glycerol

Some of the released FFA return to the circulation, attached to ___________, but the bulk is transported into the tissue

albumin

____________________ has a low Km for triacylglycerol, about one-tenth of that for the enzyme in adipose tissue. This enables the delivery of fatty acids from triacylglycerol to be redirected from adipose tissue to the heart in the starved state when the plasma triacylglycerol decreases.

Heart lipoprotein lipase

A similar redirection to the mammary gland occurs during lactation, allowing uptake of lipoprotein triacylglycerol fatty acid for ________________.

milk fat synthesis

The ____________ plays an important part in the delivery of fatty acids from VLDL triacylglycerol to adipocytes by binding VLDL and bringing it into close contact with lipoprotein lipase.

VLDL receptor

In adipose tissue, _________ enhances lipoprotein lipase synthesis in adipocytes and its translocation to the luminal surface of the capillary endothelium.

insulin

Reaction with lipoprotein lipase results in the loss of ___________.of the triacylglycerol of chylomicrons and in the loss of apo C (which returns to HDL) but not _______, which is retained.

70% to 90% | apo E

The resulting ___________ is about half the diameter of the parent chylomicron and is relatively enriched in cholesterol and cholesteryl esters because of the loss of triacylglycerol.

chylomicron remnant

Similar changes occur to VLDL, with the formation of VLDL remnants (also called ________________).

intermediate density lipoprotein (IDL)

The __________ Is responsible for the Uptake of remnant Lipoproteins.

Liver

Chylomicron remnants are taken up by the liver by __________________ , and the cholesteryl esters and triacylglycerols are hydrolyzed and metabolized.

receptor mediated endocytosis

Uptake is mediated by apo E , via two apo E-dependent receptors, the ___________________ and ___________________.

LDL (apo B-100, E) receptor and LRP-1 (LDL receptorrelated protein-1).

it acts as a ligand to facilitate remnant uptake

Hepatic lipase

it hydrolyzes remnant triacylglycerol and phospholipid

Hepatic lipase

After metabolism to IDL, VLDL may be taken up by the liver directly via the ___________ receptor, or it may be converted to LDL.

LDL (apo B-100, E)

Only _______ molecule of apo B-100 is present in each of these lipoprotein particles, and this is conserved during the transformations.

one

Thus, each LDL particle is derived from a single precursor ______________.

VLDL particle

In humans, a relatively large proportion of _________ forms LDL, accounting for the increased concentrations of LDL in humans compared with many other mammals.

IDL

________ IS METABOLIZED VIA THE LDL RECEPTOR

LDL

The liver and many extrahepatic tissues express the ______________. It is so designated because it is specific for apo B-100 but not _______, which lacks the carboxyl terminal domain of B-100 containing the LDL receptor ligand, and it also takes up lipoproteins rich in apo E.

LDL (apo B-100, E) receptor | B-48

Approximately _______ of LDL is degraded in extrahepatic tissues and _______ in the liver.

30% | 70%

A positive correlation exists between the incidence of _____________ and the plasma concentration of LDL cholesterol.

atherosclerosis

The LDL (apoB-100, E) receptor is defective in _________________, a genetic condition which blood LDL cholesterol levels are increased, causing premature atherosclerosis.

familial hypercholesterolemia

_________ TAKES PART IN BOTH LIPOPROTEIN TRIACYLGLYCEROL & CHOLESTEROL METABOLISM

HDL

________ is synthesized and secreted from both liver and intestine

HDL

However, __________ and _________ are synthesized in the liver and transferred from liver HDL to intestinal HDL when the latter enters the plasma.

apo C and apo E

In adipose tissue, _____ enhances lipoprotein lipase synthesis in adipocytes and its translocation to the luminal surface of the capillary endothelium.

Insulin

Reaction with lipoprotein lipase results in the loss of ____ to _____% of the TAG of chylomicrons and in the loss of Apo C (which returns to HDL) but not Apo E which is retained.

70-90%

The resulting _________ is about half the diameter of the pareny chylomicron and is relatively enriched in cholesterol ans cholesteryl esters because of the loss of TAG.

Chylomicron remnant

VLDL remnants:

intermediate density lipoprotein (IDL)

The _______ is responsible for the uptake of remnant lipoproteins.

Liver

Chylomicron remnant are taken up by the liver by receptor-mediated ________ and the cholesteryl esters and TAG hydrolyzed and metabolized.

Endocytosis

Uptake is mediated by Apo E via two apo E-dependent receptors, the __________ and __________.

LDL (apo B-100, E) receptor | LRP-1 (LDL receptor-related protein 1)

It acts as a ligand to facilitate remnant uptake.

Hepatic lipase

It hydrolyzes remnant triacyclglycerol and phopsholipid.

Hepatic lipase

After metabolism to IDL, VLDL may be taken up by the liver directly via the _________ or it may be converted to LDL.

LDL (apo-B100, E)

True or False: Only 2 molecule of apo-B100 is present in each of these lipoprotein particles, and this is conserved during the transformations.

False: Only ONE MOLECULE

Thus each LDL particle is derived from a single precursor _______particle.

VLDL