T5. LIPID BIOSYNTHESIS

Question 1

Why must acetyl-CoA be transported outside mitochondria for FA and cholesterol synthesis?

Answer 1

Because FA and cholesterol synthesis occur mainly in the cytosol.

Question 2

Where does fatty acid synthesis occur?

Answer 2

In the liver, mammary glands, and adipose tissues.

Question 3

What are the three stages of fatty acid synthesis?

Answer 3

Synthesis of palmitate, elongation, and unsaturation.

Question 4

Where do the first and later steps of FA synthesis occur in the cell?

Answer 4

First step in the cytosol; elongation and desaturation in the ER.

Question 5

What are the requirements for FA synthesis?

Answer 5

8 Acetyl-CoA, 7 ATP, and 14 NADPH.

Question 6

Where does NADPH primarily come from for FA synthesis?

Answer 6

The pentose phosphate pathway.

Question 7

What is the immediate precursor for FA synthesis?

Answer 7

Malonyl-CoA (3C).

Question 8

What is the end product of fatty acid synthesis?

Answer 8

Palmitic acid (16C), later converted to palmitoyl-CoA.

Question 9

What happens to palmitoyl-CoA after synthesis?

Answer 9

Transported to ER for elongation and unsaturation.

Question 10

What are the sources of acetyl-CoA?

Answer 10

Lactic fermentation (via pyruvate), dietary proteins, and TAG lipolysis.

Question 11

Can pyruvate be used to make fatty acids?

Answer 11

Yes, glucose can be converted to fats through pyruvate.

Question 12

Can fatty acids be used for gluconeogenesis?

Answer 12

No, because the conversion of pyruvate to acetyl-CoA is irreversible.

Question 13

How is acetyl-CoA transported to the cytosol?

Answer 13

Converted to citrate in mitochondria, which crosses into cytosol.

Question 14

What happens to citrate in the cytosol?

Answer 14

Converted to oxaloacetate and acetyl-CoA by citrate lyase.

Question 15

What happens to oxaloacetate in the cytosol after citrate cleavage?

Answer 15

Reduced to malate by malate dehydrogenase.

Question 16

What are two possible fates of malate in the cytosol?

Answer 16

Transport back into mitochondria or converted to pyruvate via malic enzyme.

Question 17

What does malic enzyme generate during malate decarboxylation?

Answer 17

NADPH.

Question 18

What happens to cytosolic pyruvate?

Answer 18

Enters mitochondria and is carboxylated to oxaloacetate by pyruvate carboxylase.

Question 19

What is the rate-limiting step of palmitate synthesis?

Answer 19

Formation of malonyl-CoA from acetyl-CoA.

Question 20

Which enzyme catalyzes formation of malonyl-CoA?

Answer 20

Acetyl-CoA carboxylase.

Question 21

What cofactors are required for acetyl-CoA carboxylase function?

Answer 21

Biotin carried by biotin carrier protein (BCP).

Question 22

What are the three domains of acetyl-CoA carboxylase?

Answer 22

Biotin carrier, biotin carboxylase, and transcarboxylase.

Question 23

What enzyme in gluconeogenesis performs a similar role to acetyl-CoA carboxylase?

Answer 23

Pyruvate carboxylase.

Question 24

How does citrate regulate acetyl-CoA carboxylase?

Answer 24

High citrate promotes polymerization of the enzyme, activating it.

Question 25

How does fatty acid synthase affect acetyl-CoA carboxylase?

Answer 25

It acts as an allosteric inhibitor.

Question 26

How do glucagon and adrenaline affect acetyl-CoA carboxylase?

Answer 26

They inhibit it via AMPK activation.

Question 27

How does AMPK inhibit acetyl-CoA carboxylase?

Answer 27

By phosphorylating serine groups.

Question 28

How does insulin affect acetyl-CoA carboxylase?

Answer 28

It activates the enzyme by promoting dephosphorylation.

Question 29

Which molecule activates phosphatase 2A, enhancing acetyl-CoA carboxylase activity?

Answer 29

Xylulose-5-phosphate.

Question 30

What is fatty acid synthase?

Answer 30

A multifunctional enzyme complex with 7 different activities.

Question 31

What prosthetic group does ACP use?

Answer 31

4’-phosphopantetheine.

Question 32

To what does phosphopantetheine bind in ACP?

Answer 32

A serine residue.

Question 33

What is the role of ACP in fatty acid synthesis?

Answer 33

It binds malonyl-CoA.

Question 34

What does MAT (malonyl-CoA-ACP-transferase) do?

Answer 34

Transfers malonyl-CoA and acetyl-CoA.

Question 35

What does KS (β-ketoacyl-ACP synthase) do?

Answer 35

Binds acetyl-CoA and catalyzes condensation.

Question 36

What are the remaining activities of fatty acid synthase?

Answer 36

KR (reductase), DH (dehydrase), ER (reductase), and TE (thioesterase).

Question 37

Where is the acetyl group from acetyl-CoA transferred during synthesis?

Answer 37

To the Cys-SH group of KS.

Question 38

Where is the malonyl group from malonyl-CoA transferred?

Answer 38

To the -SH group of ACP.

Question 39

What are the 4 reactions in each cycle of FA synthesis?

Answer 39

Condensation, reduction, dehydration, and another reduction.

Question 40

What does KS do during condensation?

Answer 40

Combines acetyl and malonyl to form acetoacyl and release CO₂.

Question 41

What does KR do?

Answer 41

Reduces acetoacyl to hydroxybutyryl using NADPH.

Question 42

What does DH do?

Answer 42

Removes water from hydroxybutyryl.

Question 43

What does ER do?

Answer 43

Reduces the double bond to form butyryl using NADPH.

Question 44

What happens after 7 cycles of fatty acid synthesis?

Answer 44

Palmitoyl (16C) is released by TE (thioesterase).

Question 45

How many cycles are needed to synthesize palmitate?

Answer 45

Seven cycles.

Question 46

What substrates are needed for one cycle of fatty acid synthesis?

Answer 46

One acetyl-CoA and one malonyl-CoA.

Question 47

What enzymes perform elongation and desaturation?

Answer 47

Elongases and desaturases.

Question 48

Where does elongation occur?

Answer 48

In mitochondria and ER.

Question 49

Where does desaturation occur?

Answer 49

In the ER.

Question 50

Where can desaturases introduce double bonds?

Answer 50

At carbons 4, 5, 6, and 9.

Question 51

Can humans introduce double bonds beyond C9?

Answer 51

No.

Question 52

What important molecules are synthesized from essential fatty acids?

Answer 52

Prostaglandins, leukotrienes, and thromboxanes.

Question 53

Where does the elongation of palmitic acid take place and how?

Answer 53

In mitochondria through a reverse process of β-oxidation (except for the final reduction step), and in the ER where malonyl-CoA condenses with acyl-CoA followed by two NADPH-dependent reduction reactions using CoA instead of ACP.

Question 54

What are the enzymes involved in fatty acid desaturation and where are they located?

Answer 54

A complex of desaturase + cytochrome b5 + flavoprotein, located in the smooth ER.

Question 55

How does the desaturase complex function in introducing double bonds?

Answer 55

Acts like a mini ETC, oxidizing FA and NADH with molecular oxygen (4e- total: 2 from NADH, 2 from FA double bond formation).

Question 56

What is the final product of fatty acid desaturation?

Answer 56

A fatty acid with a newly introduced double bond (unsaturated FA).

Question 57

When does fatty acid synthesis get activated in the cell?

Answer 57

When the cell has sufficient energy and excess nutrients, which are converted into fatty acids (TAGs).

Question 58

What is the main regulatory enzyme in fatty acid synthesis and how is it regulated?

Answer 58

Acetyl-CoA carboxylase; regulated allosterically, through covalent modification, and gene expression.

Question 59

What hormones regulate acetyl-CoA carboxylase?

Answer 59

Insulin increases its activity; glucagon and malonyl-CoA regulate it through inhibition and feedback.

Question 60

How does malonyl-CoA regulate fatty acid metabolism?

Answer 60

Inhibits carnitine acyltransferase I (CAT I), thus blocking fatty acid oxidation during synthesis.

Question 61

Where does TAG synthesis occur in the body and in the cell?

Answer 61

In adipose tissue, liver, mammary glands; subcellularly in the ER and outer mitochondrial membrane.

Question 62

What are the two main stages of TAG synthesis?

Answer 62

Formation of DAG-3P and its conversion into TAG.

Question 63

How is G3P formed in tissues for TAG synthesis?

Answer 63

Mainly through reduction of DHAP using NADH and G3P dehydrogenase.

Question 64

Why can't all tissues use glycerol directly for TAG synthesis?

Answer 64

Glycerol kinase is only present in the liver and kidney; other tissues lack this enzyme.

Question 65

What forms when two fatty acids are added to G3P?

Answer 65

Phosphatidic acid.

Question 66

What prevents a third FA from binding to G3P initially?

Answer 66

The enzyme is phosphorylated, preventing the third FA from binding.

Question 67

How is DAG converted to TAG?

Answer 67

Phosphatidic acid loses a phosphate group via Lipin, then a third FA is added by acyl transferase to form TAG.

Question 68

How is TAG synthesis regulated?

Answer 68

By substrate availability, acyl transferase activity, and insulin.

Question 69

What substrates contribute to TAG synthesis and where do they come from?

Answer 69

Glucose from carbohydrates and amino acids from proteins in the diet.

Question 70

What role does insulin play in TAG synthesis?

Answer 70

Stimulates conversion of acetyl-CoA and fatty acids from glucose and amino acids.

Question 71

Where is cholesterol synthesized and how much comes from each site?

Answer 71

Liver (50–70%), adrenal cortex/sex glands (10–22%), intestine (7.18%), and some from diet.

Question 72

Can cholesterol be degraded?

Answer 72

No, it can only be converted into other molecules like steroid hormones and bile salts.

Question 73

What are key functions of cholesterol in the body?

Answer 73

Membrane component, precursor of bile salts, and steroid hormones.

Question 74

What is the first step of cholesterol synthesis and where does it happen?

Answer 74

Acetyl-CoA → HMG-CoA in the cytosol.

Question 75

What is the rate-limiting step of cholesterol synthesis?

Answer 75

HMG-CoA → Mevalonate via HMG-CoA reductase in the ER.

Question 76

How is Mevalonate processed in cholesterol synthesis?

Answer 76

Activated to isopentenyl (5C) using 3 ATP; then condensed to form squalene (30C) → lanosterol → cholesterol (27C) after 19 reactions.

Question 77

What are the 3 levels of cholesterol regulation covered in this topic?

Answer 77

Regulation of HMG-CoA reductase, LDL receptor synthesis, and esterification rate via ACAT.

Question 78

How is HMG-CoA reductase regulated allosterically?

Answer 78

High cholesterol levels inhibit the enzyme.

Question 79

How is HMG-CoA reductase regulated hormonally?

Answer 79

Insulin activates via dephosphorylation; glucagon activates AMPK, which phosphorylates and inactivates it.

Question 80

How does cholesterol level affect LDL receptor synthesis?

Answer 80

High cholesterol inhibits receptor synthesis.

Question 81

What long-term control regulates cholesterol esterification?

Answer 81

Phosphorylation of ACAT enzyme.

Question 82

How is expression of HMG-CoA reductase gene regulated?

Answer 82

By the intracellular cholesterol concentration.

Question 83

What are statins and how do they work?

Answer 83

Competitive, partial, reversible inhibitors of HMG-CoA reductase; mimic HMG-CoA with 1000–10000× higher affinity.