Chol

Question 1

What are the main phases of cholesterol biosynthesis?

Answer 1

1. Synthesis of Mevalonate from Acetate 2. Conversion of Mevalonate to Activated Isoprenes 3. Condensation of Activated Isoprene Units to Form Squalene 4. Conversion of Squalene to Four-Ring Steroid Nucleus

Question 2

What is the role of Cyt P450 in cholesterol metabolism?

Answer 2

Cyt P450 enzymes function as mixed-function oxidases, facilitating hydroxylation reactions that increase water solubility of substrates.

Question 3

What are the main cholesterol derivatives?

Answer 3

• Steroid hormones * Bile acids * Vitamin D * Cholesteryl esters

Question 4

Fill in the blank: Cholesterol is synthesized from _______.

Answer 4

Acetyl-CoA

Question 5

What is the first step in the synthesis of Mevalonate?

Answer 5

2 Acetyl-CoA → Acetoacetyl-CoA, catalyzed by acetyl-CoA acyl transferase.

Question 6

What is the rate-limiting step in cholesterol synthesis?

Answer 6

Conversion of HMG-CoA to Mevalonate, catalyzed by HMG-CoA reductase.

Question 7

What are the activated isoprene units produced from mevalonate?

Answer 7

• Δ3-isopentyl pyrophosphate * Dimethylallyl pyrophosphate

Question 8

How many ATP molecules are required to create each of the six activated isoprenes?

Answer 8

Three ATP molecules are used.

Question 9

What is the cyclization product of squalene in animals?

Answer 9

Lanosterol

Question 10

What leads to the formation of atherosclerosis?

Answer 10

Pathological accumulation of cholesterol leading to obstruction of blood vessels.

Question 11

What is the function of bile acids?

Answer 11

They aid in the digestion of fats and act as emulsifiers.

Question 12

What regulates cholesterol metabolism at several levels?

Answer 12

• Covalent modification of HMG-CoA reductase * Transcriptional regulation of HMG-CoA gene * Proteolytic degradation of HMG-CoA reductase * Activation of ACAT * Transcriptional regulation of LDL receptor

Question 13

What is familial hypercholesterolemia characterized by?

Answer 13

Extremely high blood levels of cholesterol due to a defective LDL receptor.

Question 14

What do statin drugs inhibit?

Answer 14

HMG-CoA reductase

Question 15

What process protects against atherosclerosis?

Answer 15

Reverse cholesterol transport by HDL

Question 16

Fill in the blank: Steroid hormones synthesis occurs in the _______.

Answer 16

Mitochondria of steroidogenic tissues

Question 17

What are the two classes of steroids synthesized in the adrenal gland?

Answer 17

• Mineralcorticoids * Glucocorticoids

Question 18

What is the primary transporter of cholesterol in the blood?

Answer 18

Plasma lipoproteins

Question 19

What happens to cholesteryl esters in terms of solubility?

Answer 19

They are more nonpolar than cholesterol.

Question 20

What activates ACAT?

Answer 20

Cholesterol

Question 21

What is the function of apolipoproteins?

Answer 21

They are specific carrier proteins that transport lipids in the blood.

Question 22

True or False: Insulin leads to the phosphorylation and inactivation of HMG-CoA reductase.

Answer 22

False

Question 23

What is the metabolic fate of cholesterol after synthesis?

Answer 23

• Export as bile acids * Used for membrane synthesis in liver * Used as a precursor for steroid hormones and vitamin D

Question 24

What is the effect of glucagon and epinephrine on HMG-CoA reductase activity?

Answer 24

They lead to phosphorylation and reduce its activity.

Question 25

What is the primary role of HDL in cholesterol metabolism?

Answer 25

To remove cholesterol from peripheral tissues and transport it to the liver.

Question 26

What process increases the water solubility of substrates?

Answer 26

Hydroxylation ## Footnote Hydroxylation makes substrates easier for transport in blood and excretion by urine.

Question 27

Where does steroid hormone synthesis occur?

Answer 27

In mitochondria of steroidogenic tissues: placenta, ovaries, testes, and adrenal cortex ## Footnote These tissues are responsible for producing steroid hormones.

Question 28

What is the role of Cytochrome P450s in steroidogenic tissues?

Answer 28

Used to hydroxylate intermediates in the conversion of cholesterol to steroid hormones ## Footnote P450s are found associated with the inner mitochondrial and microsomal membranes.

Question 29

What is the function of P450 in the liver?

Answer 29

Hydroxylates intermediates in the conversion of cholesterol to bile acid and hydroxylates cholecalciferol to 25-hydroxycholecalciferol ## Footnote This process is crucial for the metabolism of cholesterol and vitamin D.

Question 30

What does hydroxylation affect in foreign compounds and drugs?

Answer 30

Activation or inactivation, changing its level of toxicity and solubility ## Footnote Hydroxylation is important for drug metabolism.

Question 31

What is the role of P450 in the kidney regarding vitamin D3?

Answer 31

Hydroxylates vitamin D3 to its biologically active 1,25-dihydroxylated form ## Footnote This activation is essential for vitamin D's biological functions.

Question 32

What is an activated precursor in the biosynthesis of many biomolecules?

Answer 32

Isopentenyl pyrophosphate ## Footnote This compound is involved in the synthesis of cholesterol, vitamins A, E, and K, and ubiquinone.

Question 33

What is prenylation?

Answer 33

Anchoring of proteins to the inner surface of cellular membrane by covalent attachment to an isoprenoid ## Footnote This process is important for protein localization and function within the cell.

Question 34

precursor for all steroids

Answer 34

Cholesterol

Question 35

Cholesterol Structure

Answer 35

27 carbon atoms Four fused rings • Peripheral side chain • Only one double bond (C=C)

Question 36

All of its carbon atoms are provided by

Answer 36

acetate

Question 37

Synthesis of Mevalonate from Acetate

Answer 37

2 Acetyl-CoA Acetyoacetyl-CoA – Catalyzed by acetyl-CoA acyl transferase Acetyl-CoA + Acetoacetyl-CoA  -hydroxyl--methylglutaryl-CoA HMG-CoA – Catalyzed by HMG-CoA synthase HMG-CoA + 2 NADPH Mevalonate – Catalyzed by HMG-CoA reductase

Question 38

The two activated isoprenes join ———- displacing one set of diphosphates  forms

Answer 38

head-to-tail, Geranyl

Question 39

Six Activated Isoprene Units Condense to Form Squalene

Answer 39

two isoprenes join head-to-tail, Geranyl pyrophopshate • Geranyl pyrophosphate + isopentenyl pyrophosphate forms 15-C Farnesyl pyrophosphate • Two farnesyl pyrophosphates join head-to-head to form phosphate- free Squalene

Question 40

Enzyme: Two farnesyl pyrophosphates join head-to-head to form phosphate- free Squalene

Answer 40

Squalene synthase

Question 41

Conversion of Squalene to Four-Ring Steroid Nucleus

Answer 41

Squalene monooxygenase adds one oxygen from O2 to the end of the squalene chain  forms squalene 2,3-epoxide  A mixed-function oxidase  requires NADPH

Question 42

correlate with atherosclerosis

Answer 42

Very high LDL-cholesterol

Question 43

associated with heart disease

Answer 43

Low HDL-cholesterol levels

Question 44

Statins

Answer 44

competitive inhibitors of HMG-CoA reductase