Cholesterol Metabolism Flashcards

1
Q

Cholesterol is a precursor of which substances

A
Bile acids (in liver) 
Steroid hormones (adrenal cortex, gonads) 
Vitamin D (skin)
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2
Q

Major tissue sites of cholesterol metabolism

A

Liver, intestine, adrenal cortex, ovaries, testes, placenta

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3
Q

Where in cells does cholesterol metabolism occur

A

cytosol and SER

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4
Q

Which molecule are all the carbons for cholesterol metabolism derived

A

Acetyl CoA

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5
Q

During cholesterol synthesis, which is the first sterol to be produced

A

Lanosterol (30C)

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6
Q

Cholesterol has how many carbons

A

27

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7
Q

Which sterol in cholesterol metabolism is needed for viitamin D3 production

A

7-dehydrocholesterol (27C)

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8
Q

Which enzyme converts 7-dehydrocholesterol to cholesterol

A

7-dehydrocholesterol 7-reductase

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9
Q

Which enzyme controls the rate-limiting step of cholesterol synthesis

A

HMG CoA reductase

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10
Q

What are the four regulatory steps in cholesterol synthhesis

A
  1. Sterol-dependent regulation of gene expression
  2. Sterol accelerated enzyme degradation
  3. Covalent modification (phosphorylationdephosphorylation)
  4. Hormonal regulation
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11
Q

The regulatory mechanisms in cholesterol metabolism act on which enzyme

A

HMG CoA synthase

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12
Q

Which transcription factor controls expression of the gene for HMG CoA reductase

A

SREBP-2 (sterol regulatory element-binding protein-2)

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13
Q

Sterol regulatory element-binding protein-2 is an integral protein in which organelle membrane

A

ER membrane

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14
Q

Sterols bind to which protein when cholesterol levels are high to inhibit cholesterol synthesis

A

SCAP (SREBP Clevage Activating Protein)

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15
Q

SCAP binds to which protein in the ER membrane when cholesterol levels are high retain SREBP in the ER

A

Insig proteins (Insulin induced gene products)

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16
Q

What does the SREBP-1 protein do

A

upregulates expression of genes involved in fatty acid synthesis in response to insulin

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17
Q

Which molecule can covalently inactivate HMG CoA reductase

A

AMP-activated protein kinase

18
Q

Which molecule can covalently activate HMG CoA reductase

A

Protein phosphatase

19
Q

Two hormones that induce the gene for HMG CoA reductase

A

insulin and thyroxine

20
Q

Two hormones that repress the gene for HMG CoA reductase

A

Glucagon and glucocorticoids

21
Q

Drugs that are competitive inhibitors of which enzyme are used to treat hypercholesterolemia

A

HMG CoA reductase

22
Q

Dietary cholesterol (Exogenous): Transported as _____________ from the intestine to the liver and EHT

A

chylomicrons

23
Q

De novo synthesis cholesterol (Endogenous):Transported as ______ and ________ from the liver to the EHT

A

VLDL and LDL

24
Q

Reverse Transport of cholesterol: Transported as _________ from the EHT to the liver

A

HDL

25
Q

What is the name of the molecule that cholesterol is stored as

A

cholesteryl esters

26
Q

what is the enzyme needed to convert cholesterol to cholesteryl esters

A

ACAT (acyl coA cholesterol acyl transferase)

Cholesterol + Acyl CoA —> cholesteryl ester + CoA

27
Q

Two way in which cholesterol is excreted

A

It is converted into bile acid and salts

it is secreted into bile and excreted in feces

28
Q

What are neutral fecal sterols

A

coprostanol & cholestanol together with cholesterol

29
Q

Smith-Lemli-Opitz syndrome (SLOSI is due to a partial deficiency in which enzyme

A

7-dehydrocholesterol-7-reductase

30
Q

What clinical presentation can result from a deficiency in 7-dehydrocholesterol-7-reductase

A

Multisystem embryonic malformations

  • microencephaly, short nasal root, high arched palate, cleft palate
  • CNS defects, polydactyly
  • Severe mental & growth retardation
31
Q

What are four causes of hyperchlesterolemia

A
  1. Diabetes mellitus
  2. Familial disorders (Lipoprotein metabolism)
  3. Hypothyroidism
  4. Nephrotic syndrome
32
Q

Where does the synthesis of bile acids occur

A

liver

33
Q

What is the starting molecule for bile acid synthesis

A

cholesterol

34
Q

Which enzyme is needed for synthesis of bile acids

A

7 alpha-hydroxylase

35
Q

Addition of which two molecules convert Cholic acid and Chenodeoxycholic acid to conjugated bile salts

A

Glycine and Taurine

36
Q

In which organ is bile concentrated

A

gall bladder

37
Q

Which vitamin is needed during bile acid synthesis

A

vitamin C

38
Q

What are the functions of bile acids/salts

A
  1. help in lipid emulsification during lipid digestion and absorption
  2. solubilize dietary lipids
  3. facilities action of pancreatic lipases
  4. lipids are more readily absorbed by the intestine
  5. Solubilizes cholesterol present in the bile
39
Q

What two processes do bile acids undergo in the intestine are they have been used

A

Deconjugation and dehydroxylation

40
Q

What are the two main secondary bile salts

A

deoxy cholic acid and lithocholic acid

41
Q

What are the two causes of cholelithiasis

A

increased excretion of cholesterol in bile

decreased availability of bile salt in the bile