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

phosphatidic acid.

Question 2

The enzyme system for adding double bonds to saturated fatty acids requires all of the following except:

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

Answer 2

ATP.

Question 3

Which of the following 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.

Answer 3

NADPH is produced in the nucleus by malic enzyme.

Question 4

Which of these statements 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 5

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).

Question 6

Which of these statements 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 7

All glycerol-containing phospholipids are synthesized from:

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

Question 8

Which one of the following statements best 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 above

Question 9

Palmitoyl-CoA,,is a direct precursor of:

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

Question 10

Which of the following 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 11

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 above

Question 12

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 13

Which of the following is not required in the synthesis of fatty acids?

A)Acetyl-CoA
B)Biotin
C)HCO₃^- (CO₂)
D)Malonyl-CoA
E)NADH

Question 14

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 15

Which of these 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 16

Which of the following 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 17

Which of the following 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 18

In comparing fatty acid biosynthesis with $\beta$ oxidation of fatty acids,which of the following statements 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 19

In E.coli the synthesis of phosphatidylethanolamine directly involves:

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

Question 20

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.

Question 21

Which of these statements 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 22

Cholesterol is synthesized from:

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

Question 23

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

Question 24

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

Question 25

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 26

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

Question 27

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 28

Which of the following 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 29

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

Question 30

Which of the following is derived from a sterol?

A)Bile salts
B)Gangliosides
C)Geraniol
D)Phosphatidylglycerol
E)Prostaglandins

Question 31

Which of the following 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 32

Which of these compounds 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 33

Which of the following contains the highest percentage of cholesteryl esters?

A)Chylomicrons
B)VLDL
C)LDL
D)HDL
E)None of the above contain any cholesteryl esters.

Question 34

Which of the following 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 35

CDP-diglyceride is not involved in the biosynthesis of:

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

Question 36

A 30-carbon precursor of the steroid nucleus is:

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

Question 37

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 38

Which of these statements 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 39

Lipoprotein particles in human blood do not contain:

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

Question 40

Chylomicrons carry in the .

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

Question 41

The synthetic compound mevinolinic acid,also called lovastatin,is a potent competitive inhibitor of HMG-CoA reductase (hydroxymethylglutaryl-CoA reductase).Predict and explain the effect of this drug on serum cholesterol levels in humans.

Question 42

Show the structure of isopentenyl pyrophosphate and of dimethylallyl pyrophosphate.Connect with a dotted line the two carbon atoms that will be joined when these two molecules condense to form the 10-carbon intermediate in cholesterol biosynthesis.

Question 43

Show the reaction that limits the rate of cholesterol synthesis from acetate,indicating the role of any cofactors that participate.

Question 44

Describe the formation of farnesyl pyrophosphate from activated isoprenyl units.

Question 45

The synthesis of cholesterol begins with the condensation of a four-carbon unit from _______________ with the two carbons of acetyl-CoA to form a six-carbon derivative.Give its structure,and circle the atoms that originated in the acetyl-CoA.

Question 46

When a 10-carbon unit and a 5-carbon unit condense to a 15-carbon intermediate in the pathway to cholesterol,the mechanism of condensation is basically different from that of the condensation of two 15-carbon units to the 30-carbon compound squalene.Describe the two condensations in enough chemical detail to illustrate the difference between them.(You should show relevant structures. )

Question 47

Describe (briefly)two classes of genetic defects in humans that could produce an elevated blood serum cholesterol level.

Question 48

Show the pathway from acetyl-CoA to mevalonate,indicating the roles of any cofactors.

Question 49

Describe the process by which cholesterol esters in the bloodstream enter cells.

Question 50

Explain briefly why we require fats in our diets.

Question 51

What are plasma lipoproteins? What is their general role in mammalian metabolism?

Question 52

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

Question 53

Describe briefly the four stages in the pathway from acetyl-CoA to lanosterol.

Question 54

Describe two basic strategies for activating precursors in the biosynthesis of phospholipids.

Question 55

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

Question 56

Show the two different biosynthetic pathways from phosphatidic acid to phosphatidylcholine.You may use shorthand notation for phosphatidic acid,but name any cofactors required in the path and show where they are involved.

Question 57

Show the pathway from mevalonate to dimethylallyl pyrophosphate,indicating where any cofactors participate.

Question 58

Shown below is a molecule of squalene,which is composed of 6 isoprene units.Draw lines to indicate the junctions between the six isoprene units.