ME04 - Lipid Transport and Storage Flashcards

1
Q

A biochemical assembly that contains both proteins and lipids

A

Lipoprotein

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2
Q

Why are lipids are transported in the plasma as lipoproteins?

A

Because lipids are insoluble in an aqueous medium

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3
Q

Plasma lipids components

A

TAG, phospholipids, cholesterol, and cholesteryl esters (CE), and free fatty acids

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4
Q

Classification of lipoproteins

A

Chylomicrons, VLDL, IDL, LDL, HDL

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5
Q

Carry triacylglycerol & other dietary lipids from the intestines to the liver and to adipose tissue

A

Chylomicrons

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6
Q

Carry newly synthesized triacylglycerol from the liver to adipose tissue.

A

Very low density lipoproteins (VLDL), pre- b -lipoproteins

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7
Q

Intermediate between VLDL and LDL. They are not usually detectable in the blood.

A

Intermediate density lipoproteins(IDL)

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8
Q

Carry cholesterol from the liver to cells of the body. Sometimes referred to as the “bad cholesterol” lipoprotein.

A

Low density lipoproteins (LDL), b -lipoproteins

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9
Q

Collects cholesterol from the body’s tissues, and brings it back to the liver. Sometimes referred to as the “good cholesterol” lipoprotein.

A

High density lipoproteins (HDL), a- lipoproteins

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10
Q

Lipid-binding proteins which are the constituents of the plasma lipoproteins

A

Apolipoproteins

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11
Q

Characteristic of Apolipoproteins

A

The amphipathic (detergent-like) properties

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12
Q

Function of Apolipoproteins

A

Solubilize the hydrophobic lipid constituents of lipoproteins
Serve as enzyme co- factors, receptor ligands, and lipid transfer carriers

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13
Q

Corresponding Apolipoproteins with Lipoproteins

A

Chylomicrons B-48
VLDL, IDL, HDL B-100

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14
Q

METABOLISM OF CHYLOMICRONS

A

Chylomicrons are synthesized in intestinal cells
The TAG is from dietary lipid
Major apoprotein is Apo B-48

  1. Chylomicrons travel through the lymph into the blood
  2. Apo C II , the activator of lipoprotein lipase (an enzyme which hydrolyzes lipids in lipoproteins), and Apo E are transferred to nascent (newly synthesized) chylomicrons from HDL.
  3. Mature chylomicrons are then formed
  4. In peripheral tissues (adipose and muscle), TAG is digested by lipoprotein lipase
  5. Chylomicron remnants interact with liver receptors and are taken up by endocytosis
  6. Contents of remnants are degraded by lysosomal enzymes and the products (amino acids, fatty acids, glycerol, cholesterol) are reutilized
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15
Q

METABOLISM OF VLDL

A
  1. VLDL synthesized in liver after a high- carbohydrate meal
  2. VLDL formed from TAG that are packaged with Cholesterol, Apo proteins (esp. Apo B- 100 w/c is recognized by hepatic receptors), and phospholipids, and are released to the bloodstream
  3. In peripheral tissues (adipose, muscle), VLDL TAG are digested by lipoprotein lipase, and VLDL is converted to IDL
  4. IDL returns to the liver and is degraded
  5. IDL may also be degraded by lipoprotein lipase to LDL
  6. LDL reacts with receptors on various cells, is taken up by endocytosis in the liver, and is digested by lysosomal enzymes
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16
Q

METABOLISM OF HDL

A

HDL synthesized by liver and released into blood

  1. HDL cholesterol is converted to cholesteryl ester by LCAT (lecithin-cholesterol acyltransferase) which is activated by Apo A I
  2. A fatty acid from position 2 of lecithin forms an ester with the 3-hydroxyl group of cholesterol, producing lysolecithin and cholesterol ester
  3. As choleterol ester accumulates, HDL becomes spheroidal
  4. HDL particles are taken up by the liver and hydrolyzed
17
Q

Major HDL protein

A

Apo A

18
Q

Apolipoprotein that activates lipoprotein lipase

A

Apo C II - which is transferred by HDL to chylomicrons and VDL

19
Q

Apolipoprotein that serves as recognition factor for cell surface receptors

A

Apo E

20
Q

Apolipoproteins that are transferred back to HDL after TAG digestion

A

Apo C II and Apo E

21
Q

Role of LIVER

A

(1) It facilitates the digestion and absorption of lipids by the production of bile, which contains cholesterol and bile salts synthesized within the liver de novo or from uptake of lipoprotein cholesterol
(2) It actively synthesizes and oxidizes fatty acids
(3) It synthesizes triacylglycerols and phospholipids
(4) It converts fatty acids to ketone bodies (ketogenesis)
(5) It plays an integral part in the synthesis and metabolism of plasma lipoproteins

22
Q

Main storage area of triacylglycerol

A

Adipose Tissue - Cannot utilize glycerol to synthesize TAG, since it has no glycerol kinase

23
Q

What factors stimulates and inhibits the main storage area of TAGs

A

Storage stimulated by insulin and nicotinic acid, PGE; and

Inhibited by glucagon, epinephrine, norepinephrine, thyroid hormone, growth hormone, and steroids

24
Q

MOA of Caffeine on the storage of TAGs

A

Caffeine, which inhibits phosphodiesterase, stimulates lipolysis

25
Q

Clinical Correlation on the Imbalance in the Rate of Triacylglycerol Formation & Export AND EXCESS USE OF ETHANOL

A

Fatty Liver&raquo_space; Leads to Cirrhosis

26
Q

Rationale why there is fatty liver result with imbalance in the rate of TAG formation and excess Ethanol

A

The NADH generated competes with reducing equivalents from other substrates, including fatty acids, for the respiratory chain, inhibiting their oxidation and causing increased esterification of fatty acids to form triacylglycerol, resulting in the fatty liver

27
Q

How does alcohol competes with drug metabolism

A

Acetaldehyde is also dehydrogenated to acetate, which will be converted to acetyl CoA
Increased NADH also leads to lactate accumulation

28
Q

An enzyme which becomes more active in chronic alcoholics.

A

cyt P450 enzyme called MEOS (microsomal ethanol oxidizing system) - utilizes NADPH and O2

29
Q

Other causes of Fatty Liver

A

Malnutrition (lack of protein) Abetalipoproteinemia
Drugs and toxins

30
Q

Types of adipose tissue that is present in many newborn or hibernating mammals as well as migratory birds
Its primary purpose is to generate body heat

A

Brown Adipose Tissue

31
Q

Difference of Brown and White Adipose Tissue

A

White adipocytes (fat cells), which contain a single, large fat vacuole, brown adipocytes contain several smaller vacuoles and a much higher number of mitochondria
Brown fat also contains more capillaries since it has a greater need for oxygen than most tissues.

32
Q

Effect of INSULIN on Lipid Transport

A

Reduce the release of free fatty acids into the bloodstream
Enhance glucose uptake into adipose tissues via the GLUT 4 transporter
Increases the activity of PDH and Acetyl CoA carboxylase, stimulating fat synthesis

33
Q

Hormones that accelerate the release of free fatty acids from adipose tissue stores

A

Epinephrine, glucagon, ACTH, TSH, GH, and vasopressin

34
Q

A newly discovered body weight regulatory hormone that stimulates lipolysis

A

Leptin

35
Q

Lipid droplet-associated protein
Protein involved in the formation of lipid droplets in adipocytes

A

Perilipin

36
Q

Function of Perilipin

A

Inhibits lipolysis by preventing access of lipases to the TAGs
With activation by protein kinase A, perilipins translocate away from the lipid droplet and allow hormone-sensitive lipase to hydrolyze the adipocyte triglycerides to release nonesterified fatty acids (NEFA).

37
Q

Stimulates/Activates Perilipin

A

Protein Kinase A

38
Q

SUMMARY

A

Cholesterol is produced mainly in the liver and intestine
Cholesterol and its esters are transported via lipoproteins
All the carbons of cholesterol come from Acetyl CoA
The TAG of the chylomicrons and VLDL are digested by lipoprotein lipase
LDL provides cholesterol to tissues
HDL picks up cholesterol from tissues