Deck 21: Lipid Biosynthesis

Question 1

The synthesis of both glycerophospholipids and triacylglycerols involves:

A) CDP-choline.
B) CDP-diacylglycerol.
C) phosphatidate phosphatase.
D) phosphatidic acid.
E) phosphoethanolamine.

Answer 1

D

Question 2

In the synthesis of phosphatidylcholine from phosphatidylethanolamine, the methyl group donor is:

A) a tetrahydrofolate derivative.
B) choline.
C) methanol.
D) S-adenosylmethionine (adoMet).
E) serine.

Answer 2

D

Question 3

If malonyl-CoA is synthesized from ¹⁴CO₂ and unlabeled acetyl-CoA, and the labeled malonate is then used for fatty acid synthesis, the final product (fatty acid) will have radioactive carbon in:

A) every C.
B) every even-numbered C-atom.
C) every odd-numbered C-atom.
D) no part of the molecule.
E) only the omega-carbon atom (farthest carbon from C-1).

Answer 3

D

Question 4

Which statement applies to synthesis of fatty acids in E. coli extracts?

A) Acyl intermediates are thioesters of a low molecular weight protein called acyl carrier protein.
B) CO₂ or HCO₃^- is essential.
C) Reducing equivalents are provided by NADPH.
D) The ultimate source of all the carbon atoms in the fatty acid product is acetyl-CoA.
E) All of the statements apply to synthesis of fatty acids in E. coli extracts.

Question 5

In comparing fatty acid biosynthesis with $\beta$ oxidation of fatty acids, which statement is INCORRECT?

A) A thioester derivative of crotonic acid (trans-2-butenoic acid) is an intermediate in the synthetic path, but not in the degradative path.
B) A thioester derivative of D- $\beta$ -hydroxybutyrate is an intermediate in the synthetic path, not in the degradative path.
C) Fatty acid biosynthesis uses NADPH exclusively, whereas $\beta$ oxidation uses NAD⁺ exclusively.
D) Fatty acid degradation is catalyzed by cytosolic enzymes; fatty acid synthesis by mitochondrial enzymes.
E) The condensation of two moles of acetyl-CoA in the presence of a crude extract is more rapid in bicarbonate buffer than in phosphate buffer at the same pH; the cleavage of acetoacetyl-CoA proceeds equally well in either buffer.

Question 6

The rate-limiting step in fatty acid synthesis is:

A) condensation of acetyl-CoA and malonyl-CoA.
B) formation of acetyl-CoA from acetate.
C) formation of malonyl-CoA from malonate and coenzyme A.
D) the reaction catalyzed by acetyl-CoA carboxylase.
E) the reduction of the acetoacetyl group to a $\beta$ -hydroxybutyryl group.

Question 7

Which compound is NOT required in the synthesis of fatty acids?

A) acetyl-CoA
B) biotin
C) HCO₃^- (CO₂)
D) malonyl-CoA
E) NADH

Question 8

Which statement about triacylglycerol synthesis is CORRECT?

A) Humans can store more energy in glycogen than in triacylglycerols.
B) Insulin stimulates conversion of dietary carbohydrate into triacylglycerols.
C) It is not a hormone-sensitive process.
D) Mammals are unable to convert carbohydrates into triacylglycerols.
E) Phosphatidate is not on the pathway of triacylglycerol synthesis.

Question 9

Which statement is NOT true of the fatty acid synthase and the fatty acid $\beta$ -oxidation systems?

A) A derivative of the vitamin pantothenic acid is involved.
B) Acyl-CoA derivatives are intermediates.
C) Double bonds are oxidized or reduced by pyridine nucleotide coenzymes.
D) The processes occur in different cellular compartments.
E) The processes occur in the mitochondrial matrix.

Question 10

The biosynthesis of triacylglycerols from acetate occurs mainly in:

A) animals but not in plants.
B) humans after ingestion of excess carbohydrate.
C) humans with low carbohydrate intake.
D) plants but not in animals.
E) None of the answers is correct.

Question 11

In E. coli the synthesis of phosphatidylethanolamine directly involves:

A) acyl carrier protein.
B) biotin.
C) CDP-choline.
D) phosphatidylglycerol.
E) serine.

Question 12

All glycerol-containing phospholipids are synthesized from:

A) cardiolipin
B) ceramide.
C) gangliosides.
D) mevalonate.
E) phosphatidic acid.

Question 13

Which statement is NOT true of the reaction producing malonyl-CoA during fatty acid synthesis?

A) It is stimulated by citrate.
B) It requires acyl carrier protein (ACP).
C) It requires CO₂ (or bicarbonate).
D) One mole of ATP is converted to ADP + P_i for each malonyl-CoA synthesized.
E) The cofactor is biotin.

Question 14

Palmitoyl-CoA, , is a direct precursor of:

A) cholesterol.
B) malonyl-CoA.
C) mevalonate
D) sphingosine.
E) squalene.

Question 15

Which statement is NOT true of the fatty acid elongation system of vertebrate cells?

A) It involves the same four-step sequence seen in the fatty acid synthase complex.
B) It is located in the smooth endoplasmic reticulum.
C) It produces stearoyl-CoA by the extension of palmitoyl-CoA.
D) It uses malonyl-CoA as a substrate.
E) The immediate precursor of the added carbons is acetyl-CoA.

Question 16

Which statement is NOT true about precursors required for fatty acid synthesis in animal cells?

A) NADPH is produced in the cytosol by the pentose phosphate pathway.
B) NADPH is produced in the nucleus by malic enzyme.
C) Acetyl-CoA is transported out of the mitochondrion via the citrate shuttle.
D) CoA is not transported across the mitochondrial membrane.
E) Malonyl-CoA is formed in the cytosol.

Question 17

A strategy that is NOT employed in the synthesis of phospholipids is:

A) condensation of CDP-alcohol with diacylglycerol.
B) condensation of CDP-diacylglycerol with alcohol.
C) condensation of CDP-diacylglycerol with CDP-alcohol.
D) exchange of free alcohol with head group alcohol of phospholipid.
E) remodeling of head group alcohols by chemical modification

Question 18

The enzyme system for adding double bonds to saturated fatty acids does NOT require:

A) a mixed-function oxidase.
B) ATP.
C) cytochrome b₅.
D) molecular oxygen (O₂).
E) NADPH.

Question 19

Which compound can be synthesized by plants but NOT by humans?

A) linoleate [18:2( $\Delta$ ^9,12)]
B) palmitate (16:0)
C) phosphatidylcholine
D) pyruvate
E) stearate (18:0)

Question 20

Which statement about eicosanoid synthesis is TRUE?

A) An early step in the path to thromboxanes is blocked by ibuprofen.
B) Arachidonate is derived mainly by hydrolysis of triacylglycerols.
C) Aspirin acts by blocking the synthesis of arachidonate.
D) Plants can synthesize leukotrienes, but humans cannot.
E) Thromboxanes are produced from arachidonate via the "linear" path.

Question 21

Which statement is NOT a step in the uptake of cholesterol from the bloodstream into cells?

A) LDL containing ApoB-100 is recognized by the LDL receptor.
B) LDL bound to the LDL receptor leads to endocytosis of the complex.
C) The cholesteryl esters in the LDL are hydrolyzed to release free cholesterol.
D) The internalized receptor is degraded.
E) The ApoB-100 protein is degraded.

Question 22

Which statement about cholesterol synthesis is TRUE?

A) Cholesterol is the only known natural product whose biosynthesis involves isoprene units.
B) Only half of the carbon atoms of cholesterol are derived from acetate.
C) Squalene synthesis from farnesyl pyrophosphate results in the release of two moles of PP_i for each mole of squalene formed.
D) The activated intermediates in the pathway are CDP-derivatives.
E) The condensation of two five-carbon units to yield geranyl pyrophosphate occurs in a "head-to-head" fashion.

Question 23

During fatty acid synthesis, malonyl-CoA becomes covalently attached to acyl-carrier protein via:

A) ester-bond formation to a serine.
B) thioester-bond formation to a cysteine.
C) amide-bond formation to a lysine.
D) ether-bond formation to a serine.
E) thioester-bond formation to a prosthetic group.

Question 24

Which compound(s) is/are derived from a sterol?

A) bile salts
B) gangliosides
C) geraniol
D) phosphatidylglycerol
E) prostaglandins

Question 25

Which statement is TRUE of sphingolipid synthesis?

A) All of the carbon atoms of palmitate and serine are incorporated into sphingosine.
B) CDP-sphingosine is the activated intermediate.
C) CO₂ is produced during the synthesis of ceramide from palmitate and serine.
D) Glucose 6-phosphate is the direct precursor of the glucose in cerebrosides.
E) Phosphatidic acid is a key intermediate in the pathway.

Question 26

Cholesterol is synthesized from:

A) acetyl-CoA.
B) choline.
C) lipoic acid.
D) malate.
E) oxalate.

Question 27

Which statement about the regulation of cholesterol synthesis is NOT true?

A) Cholesterol acquired in the diet has essentially no effect on the synthesis of cholesterol in the liver.
B) Failure to regulate cholesterol synthesis predisposes humans to atherosclerosis.
C) High intracellular cholesterol stimulates formation of cholesteryl esters.
D) Insulin stimulates HMG-CoA reductase.
E) Some metabolite or derivative of cholesterol inhibits HMG-CoA reductase.

Question 28

Which factor does NOT contribute to lowering the risk of atherosclerosis?

A) statin drugs
B) HDL
C) reverse cholesterol transport
D) ApoA-I
E) foam cells

Question 29

Which statement does NOT describe a difference between fatty acid synthase I (FAS I) and fatty acid synthase II (FAS II)?

A) FAS I is found in fungi, while FAS II is found in plants.
B) FAS I has no quaternary structure, while FAS II does.
C) Intermediates are not released in FAS I catalysis but are released in FAS II catalysis.
D) A single lipid product is produced from FAS I while multiple products may be produced by FAS II.
E) All of these statements describe differences between FAS I and FAS II.

Question 30

Which compound is NOT synthesized by a pathway that includes isoprene precursors?

A) natural rubber
B) plastoquinone
C) vitamin A
D) vitamin B₁₂
E) vitamin K

Question 31

Which compound(s) contain(s) the HIGHEST percentage of cholesteryl esters?

A) chylomicrons
B) VLDL
C) LDL
D) HDL
E) None of these compounds contain any cholesteryl esters.

Question 32

CDP-diglyceride is NOT involved in the biosynthesis of:

A) phosphatidylcholine.
B) phosphatidylethanolamine
C) phosphatidylglycerol.
D) phosphatidylserine.
E) sphingomyelin.

Question 33

Which compound is NOT an intermediate in the synthesis of lanosterol from acetyl-CoA?

A) isopentenyl pyrophosphate
B) malonyl-CoA
C) mevalonate
D) squalene
E) $\beta$ -hydroxy- $\beta$ -methylglutaryl-CoA (HMG-CoA)

Question 34

Lipoprotein particles in human blood do NOT contain:

A) an apolipoprotein B isoform.
B) cholesterol.
C) cholesteryl esters.
D) lecithin.
E) triglycerides.

Question 35

Which statement is FALSE concerning acetyl-CoA carboxylase?

A) It catalyzes the rate-limiting step in fatty acid synthesis.
B) This enzyme is inhibited by palmitate in mammals.
C) This enzyme is allosterically activated by citrate in mammals.
D) In mammals, this enzyme is inactivated under conditions when glycolysis is active.
E) This enzyme is classified as a ligase.

Question 36

What cofactor is required for acetyl-CoA carboxylase activity?

A) NADPH
B) thiamine pyrophosphate
C) lipoamide
D) biotin
E) both thiamine pyrophosphate and lipoamide

Question 37

A 30-carbon precursor of the steroid nucleus is:

A) farnesyl pyrophosphate.
B) geranyl pyrophosphate.
C) isopentenyl pyrophosphate.
D) lysolecithin.
E) squalene.

Question 38

Which enzyme activity is NOT part of FAS II?

A) a dehydratase
B) a thioesterase
C) a carboxylase
D) a transferase
E) a reductase

Question 39

Chylomicrons carry _____ in the _____.

A) triacylglycerols; cell
B) triacylglycerols; blood
C) cholesterols; blood
D) fatty acids; blood
E) fatty acids; cell

Question 40

Synthesis of malonyl-CoA from acetyl-CoA is MOST similar to what other reaction?

A) converion of malate into fumarate
B) conversion of pyruvate into acetyl-CoA
C) conversion of phosphoenolpyruvate into 2-phosphoglycerate
D) conversion of glutamate into $\alpha$ -ketoglutarate
E) conversion of pyruvate into oxaloacetate

Question 41

Which statement is FALSE regarding the conversion of dihydroxyacetone phosphate (DHAP) to glycerol-3-phosphate in the cytosol of adipose cells?

A) The reaction reduces C1 of DHAP.
B) This reaction creates a new chiral center.
C) This reaction requires the cofactor NADH.
D) This reaction is catalyzed by glycerol-3-phosphate dehydrogenase.
E) This reaction is catalyzed by an oxidoreductase.

Question 42

Synthesis of cardiolipin from phosphatidate, CTP, and glycerol-3-phosphate in E. coli consumes how many phosphoanhydride bonds?

A) zero
B) one
C) two
D) three
E) four

Question 43

How many phosphoanhydride bonds (net) are consumed in the conversion of mevalonate into the activated isoprene compound dimethylallyl pyrophosphate?

A) zero
B) one
C) two
D) three
E) four

Question 44

Biosynthesis of mammalian membrane phospholipids takes place in what cellular locations?

A) the lysosomal membrane and the plasma membrane
B) the plasma membrane and the smooth endoplasmic reticulum
C) the inner mitochondrial membrane and the plasma membrane
D) the smooth endoplasmic reticulum and the inner mitochondrial membrane
E) the inner mitochondrial membrane and the lysosomal membrane

Question 45

In one cycle of acetyl transfer from mitochondria to the cytosol via citrate, what other net change occurs?

A) net conversion of NADH to NADPH in the cytosol
B) net export of coenzyme A from mitochondria
C) net import of NADH from the cytosol into mitochondria
D) net consumption of 1 ATP
E) overall conversion of oxaloacetate into pyruvate

Question 46

What type of inhibitor is acetylsalicylic acid for COX-2?

A) a competitive inhibitor
B) a noncompetitive inhibitor
C) an uncompetitive inhibitor
D) a mixed inhibitor
E) None of the answers is correct.

Question 47

Which statement is FALSE regarding the formation of phosphatidylserine involving CTP activated intermediates in E. coli?

A) The nucleophile is the OH at C3 of diacylglyceol.
B) CMP acts as a leaving group.
C) This is a nucleophilic substitution reaction.
D) A product of the reaction is a phosphodiester.
E) Loss of a phosphoanhydride makes this reaction energetically favorable.

Question 48

After four rounds of fatty acid synthase activity, what size is the fatty acyl intermediate?

A) 4 carbons long
B) 5 carbons long
C) 8 carbons long
D) 9 carbons long
E) 10 carbons long

Question 49

Conversion of phosphatidylserine into phosphatidylethanolamine requires what chemical process?

A) dehydration
B) methylation
C) dehydrogenation
D) reduction
E) decarboxylation

Question 50

Which compound is NOT a substrate or product of lipin?

A) diacylglycerol
B) phosphatidic acid
C) water
D) lysophosphatidic acid
E) inorganic phosphate

Question 51

Which compound is NOT an intermediate in transfer of acetyl groups from mitochondria to the cytosol?

A) citrate
B) malate
C) oxaloacetate
D) fumarate
E) pyruvate

Question 52

Synthesis of sphingosine from palmitoyl-CoA and serine requires which enzymatic class?

A) transferases
B) oxidoreductases
C) hydrolases
D) ligases
E) All of these enzymatic classes are required.

Question 53

What is the net cost, in terms of high energy molecules, in the synthesis of squalene from acetyl-CoA?

A) 2 NADPH and 3 ATP
B) 6 NADPH and 9 ATP
C) 6 NAPDH and 18 ATP
D) 12 NADPH and 18 ATP
E) 13 NADPH and 18 ATP

Question 54

Which list ranks the compounds in order from the fewest to the greatest number of carbon atoms?

A) acetate, cholesterol, mevalonate, squalene
B) acetate, mevalonate, squalene, cholesterol
C) mevalonate, cholesterol, squalene, acetate
D) acetate, squalene, mevalonate, cholesterol
E) acetate, mevalonate, cholesterol, squalene

Question 55

Conversion of saturated fatty acyl chains to unsaturated fatty acyl chains by fatty acyl-CoA desaturase is accompanied by what other net change?

A) reduction of NAD⁺ to NADH
B) reduction of NADP⁺ to NADPH
C) reduction of O₂ to H₂O
D) reduction of oxaloacetate to malate
E) reduction of FAD to FADH₂

Question 56

Synthesis of a triglyceride from three fatty acids and glycerol costs how many ATP equivalents?

A) three
B) four
C) five
D) six
E) seven

Question 57

What effect will the presence of citrate have on the activity of acetyl-CoA carboxylase in mammals?

A) no effect
B) decreased K_0.5
C) increased K_0.5
D) decreased V_max
E) increased V_max

Question 58

Which statement is FALSE regarding acyl-carrier protein (ACP)?

A) ACP is transiently attached to malonyl-CoA during fatty acid elongation.
B) ACP contains a pantothenate-derived prosthetic group.
C) ACP carries reaction intermediates from one active site to the next in fatty acid synthesis.
D) ACP associates as a separate polypeptide with fatty acid synthase I in vertebrates.
E) Fatty acyl chains on ACP are transferred to a cysteine on $\beta$ -ketoacyl-ACP synthase during fatty acid synthesis.

Question 59

What is the source of the polar headgroup in the formation of sphingomyelin?

A) CDP-choline
B) phosphocholine
C) cardiolipin
D) phosphoserine
E) phosphatidylcholine

Question 60

Synthesis of phosphatidyl-choline from choline and diacylglycerol in mammals requires which nucleotides as other substrates?

A) ATP and UTP
B) CTP and UTP
C) ATP and CTP
D) CTP only
E) ATP, UTP, and CTP

Question 61

The reaction sequence that leads to fatty acid synthesis includes (1) condensation, (2) first reduction reaction, (3) dehydration, and (4) second reduction. Show the first reduction reaction, with any required cofactors.

Question 62

If you start with acetyl-CoA labeled with ¹⁴C in the methyl-carbon, where does the label end up in malonyl-CoA?

Question 63

Explain the triacylglycerol cycle and how drugs such as rosiglitazone (Avandia) promote this cycle and help lower fatty acid levels in the bloodstream.

Question 64

The synthesis of fatty acids and their breakdown by $\beta$ oxidation occur by separate pathways. Compare the two paths by filling in the blanks below. (Some blanks may require more than one answer.)

Question 65

Sketch the pathway from arachidonate to thromboxanes and explain how aspirin blocks the synthesis of thromboxanes.

Question 66

What statement is FALSE regarding the differences between chylomicrons and VLDL?

A) These two lipoproteins originate in different tissues.
B) Chylomicrons have a lower density than VLDL.
C) Chylomicrons contain ApoB-48 while VLDL contains ApoB-100.
D) Chylomicrons contain a lower percentage of protein compared to VLDL.
E) Chylomicrons contain an overall lower triacylglycerol percentage than VLDL.

Question 67

Conversion of VLDL into LDL is associated with what changes?

A) depletion of cholesteryl-esters
B) enrichment of the apolipoprotein ApoB-100
C) an increase in particle diameter
D) a decrease in the protein:lipid ratio
E) ApoE-mediated receptor interactions

Question 68

Show the structure of each intermediate in the conversion of $\beta$ -hydroxybutyryl-ACP to butyryl-ACP by the fatty acid synthetase complex. Show where cofactors participate. In your first intermediate, circle the carbon atoms that are derived from malonyl-CoA.

Question 69

If you perform fatty acid biosynthesis with CO₂ labeled with ¹⁴C, where does the label end up in a fatty acid?

Question 70

Explain briefly why we require fats in our diets.

Question 71

Describe the mechanism for moving acetyl-CoA produced in the mitochondrial matrix into the cytosol for fatty acid synthesis.

Question 72

What statement is FALSE regarding the regulation of HMG-CoA reductase?

A) HMG-CoA reductase is inhibited by phosphorylation.
B) Elevated levels of ATP will inhibit HMG-CoA reductase.
C) Elevated blood glucose will increase the activity of HMG-CoA reductase.
D) Statins act as competitive inhibitors for this enzyme.
E) Low cellular concentrations of cholesterol will increase expression of this enzyme and the LDL receptor.

Question 73

Which list CORRECTLY ranks the polarity, from most polar to least polar, for the listed substances?

A) cholesteryl-ester > bile salts > cholesterol
B) cholesterol > bile salts > cholesteryl-esters
C) bile salts > cholesteryl-esters > cholesterol
D) cholesteryl-esters > cholesterol > bile salts
E) bile salts > cholesterol > cholesteryl-esters

Question 74

Which lipoproteins do NOT originate from the liver?

A) chylomicrons and VLDL
B) VLDL and HDL
C) LDL and HDL
D) chylomicrons and HDL
E) VLDL and LDL

Question 75

Which statement is FALSE concerning bile salts?

A) They are more amphipathic than cholesterol.
B) They are secreted in response to fat ingestion.
C) They are synthesized in the gall bladder.
D) They are sterol derivatives.
E) They typically carry a negative charge.

Question 76

Reverse cholesterol transport is primarily associated with which lipoprotein?

A) chylomicrons
B) VLDL
C) IDL
D) LDL
E) HDL

Question 77

Which apolipoprotein is recognized by the LDL receptor?

A) ApoB-100
B) ApoC-I
C) ApoC-II
D) ApoD
E) ApoE

Question 78

Which apolipoprotein is found in chylomicrons but not in other lipoproteins?

A) ApoB-48
B) ApoB-100
C) ApoC-II
D) ApoC-III
E) ApoE

Question 79

Which protein is NOT typically found in HDL?

A) lecithin cholesterol acyl transferase (LCAT)
B) ApoE
C) ApoH
D) ApoC-I
E) ApoD

Question 80

Fatty acid synthesis and fatty acid breakdown occur by similar pathways. Describe, very briefly, four ways in which the synthetic and breakdown pathways differ.