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Biochemistry-Block 2 CC > Cholesterol, Lipoprotein Metabolism and Steroids > Flashcards

Cholesterol, Lipoprotein Metabolism and Steroids Flashcards

1
Q

____; organic compond with four fused rings arranged in a specific configuration (ABCD ring system)

A

steroids

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2
Q

____: subgroup of steroids with a hydroxyl group at the 3-position of the A-ring

A

Sterols

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3
Q

_____ is a highly hydrophobic compound, the major sterol in animal tissues

A

Cholesterol

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4
Q

Cholesterol is an essential ______ component of all animal cell membranes (~30%)

A

structural

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5
Q

Cholesterol is required to main both membrane structural ____ and ______ at different temperatures

A

integrity and fluidity

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6
Q

Cholesterol enables animal cells to dispense within the cell shape in order to ____ and ______

A

protect membrane integrity and cell viability

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7
Q

Cholesterol is a component of lipid rafts formation to facilitate _______

A

cell signaling

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8
Q

Cholesterol is the precursor for the synthesis of:
1)
2)
3)

A

1) Bile Salts
2) Steroid hormones
3) Vitamin D

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9
Q

____ cholesterol: found in membranes of all animal cell membranes

A

Free (unesterified)

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10
Q

________ cholesterol:

  • Not found in membranes
  • Most of the plasma cholesterol is in this form
A

Esterified cholesterol (cholesteryl esters)

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11
Q

Most cells have the ability to ________ ________

A

synthesize cholesterol

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12
Q

_____, _______, and _________ (adrenal cortex, testes, ovaries) contribute most significantly to the overall cholesterol pool

A

Liver, Intestine, Steroidogenic Tissues

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13
Q

_____ is the central organ that controls the overall cholesterol homeostasis (synthesis, distribution, elimination)

A

Liver

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14
Q

Name the sources of liver cholesterol:
1)
2)
3)

A

1) De Novo Synthesis
2) Diet (delivered from chylomicron remnants)
3) Delivered via HDLs (reverse cholesterol transport)

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15
Q

What is the route for cholesterol clearance from the liver?

A

Secretion into VLDL/LDL

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16
Q

In humans, _____ b/w cholesterol influx and efflux is not precise

A

the balance

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17
Q

The imbalance of cholesterol leads to a _______ of cholesterol in the tissues

A

gradual deposition

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18
Q

The gradual deposition of cholesterol particularly occurs in the __________

A

endothelial linings of blood vessels

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19
Q

Lipid depositions over time can lead to ______, causing the narrowing of blood vessels (atherosclerosis)

A

plaque formation

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20
Q

_______ leads to an increased risk of carido-, cerebro-, and peripheral vascular disease.
(making it potentially life threatening)

A

Plaque Formation/Atherosclerosis

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21
Q

Name the substrates for cholesterol synthesis: (3)

A
  • Acetyl CoA
  • Reducing equivalents NADPH
  • ATP is needed
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22
Q

When will synthesis occur? (2)

A
  • In well fed state (when all substrates are available)

- When cholesterol supply is low

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23
Q

____ of cholesterol is composed of multiple steps and broken up into 6 stages

A

Synthesis

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24
Q

List the Stages of the Synthesis of Cholesterol in Hepatocytes

A

1) Conversion of acetyl CoA to HMG CoA
2) Synthesis of mevalonate
3) Conversion of mevalonate to isoprenyl pyrophosphates w/loss of CO2
4) Conversion of isoprenyl pyrophosphates to squalene
5) Conversion of squalene to lanosterol
6) Conversion of lanosterol to cholesterol

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25
Q

What is the enzyme responsible for Stage 1) the Conversion of Acetyl CoA to HMG CoA?

A

HMG-CoA Synthase

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26
Q

Name the two isoenzymes (in the liver) for HMG-CoA Synthase

A

1) Cytosolic –for cholesterol synthesis

2) Mitochondrial–for ketone bodies

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27
Q

What is the enzyme responsible for Stage 2) Synthesis of Mevalonate?

A

HMG-CoA Reductase

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28
Q

What Step in the Synthesis of Cholesterol in Hepatocytes in Rate Limiting/Key Regulatory Step?

A

Stage 2) Synthesis of Mevalonate catalyzed by HMG-CoA reductase

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29
Q

The enzyme HMG-CoA reductase is inhibited by?

A

Statin Drugs

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30
Q

_____ is an integral membrane protein of the ER facing the cytosol

A

Mevalonate

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31
Q

____ molecules of mevalonate are required to make 1 molecule of cholesterol

A

6

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32
Q

Each molecule of mevalonate requires _____ molecules of acetyl CoA

A

3

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33
Q

Ultimately, _____ molecules of acetyl CoA are required to make 1 molecule of cholesterol

A

18

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34
Q

Many steps of the Synthesis of Cholesterol are _______

A

IRREVERSIBLE

humans lack enzymes to perform reverse reactions

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35
Q

Cholesterol ______ be metabolized to CO2 like sugars and fats

A

can NOT

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36
Q

Since the synthesis of cholesterol takes place in the ______, many intermediates are charged to make them soluble

A

cytoplasm

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37
Q

The intermediates of cholesterol are charged to make them soluble in the cytoplasm, until the formation of ______

A

squalene

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38
Q

At the point of Squalene formation, the molecule is associated with ________

A

carrier proteins

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39
Q

Regulation of Cholesterol Synthesis via HMG CoA Reductase:

Hormone Regulation:
_____ and _____ UPREGULATE HMG CoA Reductase expressions

A

Insulin and Thyroxine

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40
Q

Regulation of Cholesterol Synthesis via HMG CoA Reductase:

Hormone Regulation:
_____ and _____ DOWNREGULATE HMG CoA Reductase expressions

A

Glucagon and Glucocorticoids

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41
Q

Sterol-independent covalent modifications–> ________/_________ occurs via AMPK reflecting the energy state of the cell

A

phosphorylation/dephosphorylation

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42
Q

Describe the Sterol-DEPENDENT regulation–
1)
2)

A

enzyme gene transcription and expression via SREBP transcription factor

enzyme degradation via ubiquitination

43
Q

The intact sterol nucleus is eliminated by:
1)
2)

A

1) conversion to bile acids and bile salts (that are excreted in feces (2-3%)
2) secretion of cholesterol into the bile (transported to intestion for elimination as fecal cholesterol)

44
Q

Some of the cholesterol in the intestine is modified by ____ before excretion

45
Q

____ is a watery mix (greenish-yellow) or organic and inorganic compounds produced by liver to facilitate digestion of lipids in small intestine

46
Q

______ is the major constituent of bile produced in liver cells from bile acids

A

Bile Salts

47
Q

____ are the precursor for the synthesis of bile salts, produced in liver cells from cholesterol

A

Bile Acids

48
Q

Cholesterol –> ______ —> _______

A

Cholesterol –> Bile Acids –> Bile Salts

49
Q

_____ undergo a circulation where they are reabsorbed from the intestine and sent back to the liver to be used again

A

Bile salts

50
Q

Very small loss (

A

steroid nucleus

51
Q

_______ (gall stones) form in the gall bladder where bile is stored

A

Cholelithiasis

52
Q

Origin of gall stones: dervied from cholesterol and result from ____________ and/or ________ in the gall bladder (the bile salts are required to solubilize free cholesterol)

A

too little bile salts

too much cholesterol

53
Q

Name the possible causes of gall stones: (3)

A

1) inefficient enterohepatic cycling
2) liver dysfunction
3) other idiopathic reason

54
Q

______: spherical macromolecular complexes of lipids and specific proteins (apolipoproteins)

A

Lipoproteins

55
Q

Function of LIpoproteins

A

To transport cholesterol, fats and fat-soluble compounds in the plasma

56
Q

Types of Lipoproteins: (4)

A

Chylomicrons, VLDL, LDL, HDL

57
Q

____ transport of dietary lipid, produced in enterocytes

A

chylomicrons

58
Q

_____ - transport of newly synthesized lipids produced in hepatocytes

59
Q

______ - transport of cholesterol to the peripheral tissues

60
Q

_______ - transport of cholesterol from the periphery to the liver

61
Q

Core of Lipoproteins:

A

Neutral Lipids (TAG) and cholesteryl esters (hydrophobic)

62
Q

Lipoproteins have a ______- composed of phospholipid (PC and SM) and free cholesterol (hydrophilic)

A

polar lipid surface

63
Q

_________ _________: 11 different types of Apo proteins found in human (Apo A, ApoB, ApoC, ApoD, Apo(a)) specific for each class

A

Amphipathic Apolipoproteins

64
Q

______:

  • size varies on meal content
  • largest in size
  • least dense
  • contain highest percentage of fat
  • produced by gut cells
A

Chylomicrons

65
Q

_____:

  • similar to chylomicrons
  • produced by hepatocytes
  • smaller and more dense
  • contain high % of fat
66
Q

_______:

  • highest % of cholesterol
  • produced from VLDL via lipolysis in blood
  • carry the “bad” cholesterol
67
Q

_____:

  • contain highest % of protein
  • contain 2nd highest % of cholesterol
  • carry the “good” cholesterol
68
Q

The ____ and ____ of lipoproteins are routinely used in plasma lipid profiling as part of the separation process

A

size and density

69
Q

Metabolism of Chylomicrons:

1). Chylomicrons are formed in the ER and Golgi of intestinal mucosal cells, using _____ as scaffold protein

70
Q

Metabolism of Chylomicrons:

2). Lipids (TAG, cholesterol, PL) are transferred to ApoB-48 via _________________

A

Microsomal Transfer Protein (MTP)

71
Q

Metabolism of Chylomicrons:

3) “Nascent” chylomicrons containing DIETARY LIPIDS as well as FAT-SOLUBLE compounds (vitamins A, D, E, K) are excreted through ____________

A

plasma membrane into the lymph

72
Q

Metabolism of Chylomicrons:

4) From the lymph, they enter blood stream where chylomicrons undergo _______________ from HDL (ApoC and ApoE)

A

modifications and require additional Apo-Es

73
Q

Metabolism of Chylomicrons:

5) Peripheral cells expressing lipoprotein lipase (LPL) hydrolyze TAGS to _________.

A

FA and glycerol

74
Q

Metabolism of Chylomicrons:

6). The remaining is cleared from the blood stream by the ______ via ______

A

liver via endocytosis

75
Q

Which of the lipoproteins would you expect to vary based on recent meals?

A

Chylomicrons and VLDL

76
Q

Metabolism of VLDLs:

1) VLDLs are assembled in the ____ and ____ of liver cells
- full length Apo B-100 is used as scaffolding protein

A

ER and Golgi

77
Q

Metabolism of VLDLs:

2) VLDL are directly secreted into the blood stream, where they acquire ____ and ____ from HDLs

A

Apo C-II and Apo-E

78
Q

Metabolism of VLDLs:

3) ____ (activated by Apo C-ll) hydrolyzes VLDLs TAGs and release FA to the peripheral tissues

79
Q

Metabolism of VLDLs:

4) VLDL ______ in size and become ______ becoming VLDL “remnant” or IDL

A

decrease in size and become denser

80
Q

Metabolism of VLDLs:

5) Additional modifications transfer of cholesteryl esters from HDL to these particles transforming _____ into ____

A

VLDL into LDLs

81
Q

Metabolism of VLDLs:

6) _____ remaining in the LDL is a ligand recognized by the LDL Receptors (LDLR)
- taken up via endocytosis

82
Q

LDL-released cholesterol is immediately used for

______, _____ or ________

A

membrane assembly, steroid hormones or bile acid synthesis

83
Q

If cholesterol is not immediately used,
1)
2)

A

1) converted to CE by ACAT and stored

2) serves as major regulator of cholesterol homeostasis

84
Q

Oversupply of cholesterol will:
1)
2)
3)

A

1) Inhibit de novo synthesis of cholesterol
2) Inhibit expression of LDLR
3) Activate ACAT to produce CE

85
Q

Name the factors that increase modified LDL in circulation
1)
2)
3)

A

1) High Blood Sugar
2) Oxidative stress caused by (infection, smoking, drugs,e tc)
3) Chemicals present in tobacco smoke

86
Q

____ and _____ will have an increased risk of cardiovascular disease

A

smokers and diabetics

87
Q

It is thought that Vitamins A, E, C and other antioxidants can have a _______ effect

A

protective

88
Q

________: the efflux of cholesterol from peripheral tissues to HDL

A

Reverse Cholesterol Transport

89
Q

___(1)__ are considered “good” cholesterol. Elevated __(1)__ compared to __(2)___ are considered “good”, however the ratio of LDLs to HDLs is usually considered.

A

1) HDLs, 2) LDLs

90
Q

HDL’s _____ is produced within the liver and intestinal cells
secreted in the circulation as free apolipoprotein

91
Q

HDL;s serve as a reservoir of ______ and _____ for transfer to other lipoproteins

A

Apo CII and Apo E

92
Q

Lipoprotein Metabolism: Diseases

_____________: (familial hyperchylomicroenmia)

  • deficiency of Apo Cll or lipoprotein lipase (LPL)
  • rare, autosomal recessive
A

Type l hyperlipoproteinemia

93
Q

Lipoprotein Metabolism: Diseases

_____________: (familial hypercholesterolemia)

  • defect in LDL RECEPTOR
  • Autosomal dominant (1 in 500) VERY COMMON
A

Type lla hyperlipidemia

94
Q

What are the two types of steroid hormones?

A

Corticosteroids and Sex Hormones

95
Q

_____ is typically used in anti-inflammatory drugs

A

Cortisol (Corticosteroids)

96
Q

_______

  • control menstrual cycle
  • promote development of female secondary sex characteristics
97
Q

________

  • secretory phase of uterus and mammary glands
  • implantation and maturation of fertilized ovum
A

Progesterone

98
Q

___________

  • stimulates spermatogenesis
  • promotes development of male secondary sex characteristics
  • Promotes anabolism
  • Masculinization of the fetus
A

Testosterone

99
Q

Synthesis and secretions (of steroid hormones) occur in the: ______, _______ and ______

A

adrenal cortex, ovaries and placenta, and the testes

100
Q

What steroid hormones are produced by the adrenal cortex?

A

Cortisol, Aldosterone, Androgens

101
Q

What steroid hormones are produced by the ovaries and placenta?

A

Estrogens and Progestins

102
Q

Steroid Hormones are transported by the _____ from their sites of synthesis to their target organs

103
Q

Because of the hydrophobicity of the steroid hormones, they must be complexed with a plasma protein, _____

Biochemistry-Block 2 CC (13 decks)

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