De novo synthesis of fatty acids (Palmitic acid) MCQs With Answer

Understanding de novo synthesis of fatty acids, especially palmitic acid, is essential for B. Pharm students studying lipid biochemistry and drug action. This concise guide covers key concepts: cytosolic pathway from citrate to acetyl‑CoA, ATP‑citrate lyase, acetyl‑CoA carboxylase (biotin‑dependent) forming malonyl‑CoA, and the fatty acid synthase (FAS) complex that iteratively builds palmitate (C16:0) using NADPH. You’ll learn stoichiometry (8 acetyl‑CoA, 7 ATP, 14 NADPH), regulation by citrate, insulin and AMPK, and links to beta‑oxidation via malonyl‑CoA’s inhibition of CPT‑1. Clinical and pharmacological relevance, including FAS/ACC inhibitors and cancer metabolism, are highlighted. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. Which organelle supplies citrate for cytosolic de novo fatty acid synthesis?

  • Mitochondrion
  • Endoplasmic reticulum
  • Golgi apparatus
  • Lysosome

Correct Answer: Mitochondrion

Q2. The enzyme that converts citrate to acetyl‑CoA and oxaloacetate in the cytosol is:

  • ATP‑citrate lyase
  • Acetyl‑CoA carboxylase
  • Citrate synthase
  • Malate dehydrogenase

Correct Answer: ATP‑citrate lyase

Q3. Acetyl‑CoA carboxylase (ACC) catalyzes the formation of which key intermediate for fatty acid synthesis?

  • Acetoacetyl‑CoA
  • Malonyl‑CoA
  • Palmitoyl‑CoA
  • Citrate

Correct Answer: Malonyl‑CoA

Q4. The prosthetic group required by acetyl‑CoA carboxylase for carboxylation reactions is derived from which vitamin?

  • Biotin (vitamin B7)
  • Pantothenic acid (vitamin B5)
  • Riboflavin (vitamin B2)
  • Niacin (vitamin B3)

Correct Answer: Biotin (vitamin B7)

Q5. How many acetyl‑CoA molecules are directly incorporated into one molecule of palmitate (C16:0)?

  • 7 acetyl‑CoA
  • 8 acetyl‑CoA
  • 16 acetyl‑CoA
  • 4 acetyl‑CoA

Correct Answer: 8 acetyl‑CoA

Q6. The fatty acid synthase (FAS) complex in mammals is best described as:

  • A multienzyme complex encoded by multiple separate genes (Type II)
  • A large homodimeric multifunctional polypeptide (Type I)
  • A monofunctional enzyme working independently
  • An enzyme localized exclusively in mitochondria

Correct Answer: A large homodimeric multifunctional polypeptide (Type I)

Q7. Which carrier protein transfers acyl intermediates during fatty acid synthesis?

  • Coenzyme A only
  • Acyl carrier protein (ACP)
  • Albumin
  • Fatty acid binding protein (FABP)

Correct Answer: Acyl carrier protein (ACP)

Q8. The 4′-phosphopantetheine prosthetic group of ACP is derived from which vitamin?

  • Biotin
  • Pantothenic acid (vitamin B5)
  • Thiamine (vitamin B1)
  • Folate (vitamin B9)

Correct Answer: Pantothenic acid (vitamin B5)

Q9. Which cofactor provides reducing equivalents for the two reduction steps in each FAS cycle?

  • NADH
  • NADPH
  • FADH2
  • ATP

Correct Answer: NADPH

Q10. Approximately how many NADPH molecules are required to synthesize one molecule of palmitate?

  • 8 NADPH
  • 14 NADPH
  • 7 NADPH
  • 16 NADPH

Correct Answer: 14 NADPH

Q11. Which two pathways are the major cytosolic sources of NADPH for fatty acid synthesis?

  • Glycolysis and TCA cycle
  • Pentose phosphate pathway and malic enzyme
  • Electron transport chain and beta‑oxidation
  • Urea cycle and gluconeogenesis

Correct Answer: Pentose phosphate pathway and malic enzyme

Q12. The first condensation reaction in FAS uses which two substrates?

  • Two acetyl‑CoA molecules
  • Acetyl‑ACP and malonyl‑ACP
  • Malonyl‑CoA and palmitoyl‑CoA
  • Acetoacetyl‑ACP and NADPH

Correct Answer: Acetyl‑ACP and malonyl‑ACP

Q13. Which enzymatic activity of FAS catalyzes the release of palmitate from the enzyme complex?

  • Thioesterase
  • Dehydratase
  • Ketoreductase
  • Acyltransferase

Correct Answer: Thioesterase

Q14. Which molecule allosterically activates acetyl‑CoA carboxylase (ACC)?

  • Palmitoyl‑CoA
  • Citrate
  • AMP
  • Glucagon

Correct Answer: Citrate

Q15. AMP‑activated protein kinase (AMPK) affects ACC by:

  • Phosphorylating and activating ACC
  • Dephosphorylating and activating ACC
  • Phosphorylating and inhibiting ACC
  • Increasing ACC gene transcription acutely

Correct Answer: Phosphorylating and inhibiting ACC

Q16. Malonyl‑CoA inhibits which mitochondrial transporter to coordinate synthesis and oxidation?

  • Carnitine palmitoyltransferase‑1 (CPT‑1)
  • ATP synthase
  • Mitochondrial pyruvate carrier
  • Acyl‑CoA dehydrogenase

Correct Answer: Carnitine palmitoyltransferase‑1 (CPT‑1)

Q17. Which hormone signaling promotes dephosphorylation and activation of ACC, favoring fatty acid synthesis?

  • Glucagon
  • Adrenaline
  • Insulin
  • Cortisol

Correct Answer: Insulin

Q18. The stoichiometric ATP requirement to synthesize palmitate (for malonyl‑CoA formation) is:

  • 14 ATP
  • 8 ATP
  • 7 ATP
  • 0 ATP

Correct Answer: 7 ATP

Q19. Which enzyme in the cytosol regenerates NADPH while converting malate to pyruvate?

  • Malate dehydrogenase (mitochondrial)
  • Malic enzyme (ME1)
  • Pyruvate carboxylase
  • Citrate lyase

Correct Answer: Malic enzyme (ME1)

Q20. In mammals, fatty acid synthase deficiency would most directly decrease synthesis of which fatty acid?

  • Linoleic acid (18:2, n‑6)
  • Palmitic acid (16:0)
  • Oleic acid (18:1)** only
  • Arachidonic acid (20:4, n‑6)

Correct Answer: Palmitic acid (16:0)

Q21. Which of the following statements about malonyl‑CoA is true?

  • It directly supplies two‑carbon units and its decarboxylation drives condensation
  • It is synthesized from palmitate by ACC
  • It is exclusively produced in mitochondria
  • It is a reducing cofactor for FAS

Correct Answer: It directly supplies two‑carbon units and its decarboxylation drives condensation

Q22. Which enzyme is the rate‑limiting step for de novo fatty acid synthesis?

  • Fatty acid synthase (FAS)
  • ATP‑citrate lyase
  • Acetyl‑CoA carboxylase (ACC)
  • Citrate synthase

Correct Answer: Acetyl‑CoA carboxylase (ACC)

Q23. Which statement distinguishes FAS Type I (mammalian) from Type II (bacterial)?

  • Type I is a single multifunctional polypeptide; Type II uses separate enzymes
  • Type I uses NADH; Type II uses NADPH
  • Type I synthesizes only odd‑chain fatty acids; Type II makes even‑chain
  • Type I is localized to mitochondria; Type II is cytosolic

Correct Answer: Type I is a single multifunctional polypeptide; Type II uses separate enzymes

Q24. Which desaturase is responsible for introducing the first double bond at the Δ9 position of stearoyl‑CoA?

  • Delta‑6 desaturase
  • Stearoyl‑CoA desaturase (Δ9)
  • Delta‑12 desaturase
  • Acyl‑CoA oxidase

Correct Answer: Stearoyl‑CoA desaturase (Δ9)

Q25. Elongation of palmitate to stearate (C18:0) primarily occurs in which cellular compartment?

  • Mitochondrial matrix
  • Endoplasmic reticulum (ER)
  • Peroxisome only
  • Nucleus

Correct Answer: Endoplasmic reticulum (ER)

Q26. Which molecules are direct products when ACC converts acetyl‑CoA to malonyl‑CoA?

  • Malonyl‑CoA and ADP
  • Malonyl‑CoA and Pi
  • Malonyl‑CoA, ADP and Pi via ATP consumption
  • Malonyl‑CoA and CO2 only

Correct Answer: Malonyl‑CoA, ADP and Pi via ATP consumption

Q27. Which of the following inhibits acetyl‑CoA carboxylase activity?

  • Citrate
  • Insulin signaling
  • Palmitoyl‑CoA
  • Active protein phosphatase

Correct Answer: Palmitoyl‑CoA

Q28. Cancer cells often show upregulated fatty acid synthase (FAS). Pharmacologically targeting FAS is considered because:

  • FAS inhibition increases cholesterol synthesis exclusively
  • Rapidly proliferating cells require de novo lipids for membranes
  • FAS is the primary source of ATP in tumors
  • FAS inhibitors boost fatty acid oxidation directly

Correct Answer: Rapidly proliferating cells require de novo lipids for membranes

Q29. Which enzyme supplies cytosolic acetyl‑CoA from citrate and is often upregulated in lipogenic tissues?

  • Citrate synthase
  • ATP‑citrate lyase (ACL)
  • Acetyl‑CoA synthetase
  • Pyruvate dehydrogenase

Correct Answer: ATP‑citrate lyase (ACL)

Q30. During one FAS cycle (2‑carbon elongation), which sequence of reactions occurs?

  • Condensation → dehydration → two reductions
  • Condensation → reduction → dehydration → reduction
  • Reduction → condensation → dehydration → reduction
  • Dehydration → reduction → condensation → reduction

Correct Answer: Condensation → reduction → dehydration → reduction

Q31. Which of the following is NOT an essential fatty acid (must be obtained from diet)?

  • Linoleic acid (18:2 n‑6)
  • Alpha‑linolenic acid (18:3 n‑3)
  • Palmitic acid (16:0)
  • None of the above

Correct Answer: Palmitic acid (16:0)

Q32. Which mitochondrial process is directly limited by increased malonyl‑CoA levels?

  • Gluconeogenesis
  • Beta‑oxidation of fatty acids
  • TCA cycle flux
  • Urea cycle

Correct Answer: Beta‑oxidation of fatty acids

Q33. Which domain of FAS is responsible for reducing β‑keto intermediates using NADPH?

  • Ketoreductase (KR)
  • Dehydratase (DH)
  • Thioesterase (TE)
  • Condensing enzyme (KS)

Correct Answer: Ketoreductase (KR)

Q34. Which experimental tracer is commonly used to measure de novo lipogenesis in cells?

  • 14C‑acetate or 3H‑water incorporation into lipids
  • 32P‑ATP incorporation into DNA
  • 14C‑glucose oxidation to CO2 exclusively
  • Urine ketone measurement

Correct Answer: 14C‑acetate or 3H‑water incorporation into lipids

Q35. In bacteria, fatty acid synthesis inhibitors such as triclosan target which enzyme system?

  • Type I FAS complex
  • Type II enoyl‑ACP reductase (FabI)
  • Mammalian ACC1
  • Stearoyl‑CoA desaturase

Correct Answer: Type II enoyl‑ACP reductase (FabI)

Q36. Which factor would most increase hepatic de novo lipogenesis?

  • High AMP and fasting state
  • High carbohydrate diet and hyperinsulinemia
  • Prolonged exercise and low insulin
  • Administration of AMPK activators

Correct Answer: High carbohydrate diet and hyperinsulinemia

Q37. The decarboxylation of malonyl‑ACP during the condensation step primarily serves to:

  • Provide reducing equivalents
  • Drive the Claisen condensation thermodynamically
  • Generate NADPH
  • Release CO2 for biosynthesis

Correct Answer: Drive the Claisen condensation thermodynamically

Q38. Which isoform of ACC is most directly linked to regulation of fatty acid synthesis in lipogenic tissues?

  • ACC1 (cytosolic)
  • ACC2 (mitochondrial membrane‑associated)
  • ACC3 (peroxisomal)
  • ACC4 (nuclear)

Correct Answer: ACC1 (cytosolic)

Q39. Which enzyme introduces double bonds into fatty acids and requires O2 and cytochrome b5?

  • Fatty acid elongase (ELOVL)
  • Desaturase (e.g., stearoyl‑CoA desaturase)
  • Acyl‑CoA oxidase
  • Acyl‑protein thioesterase

Correct Answer: Desaturase (e.g., stearoyl‑CoA desaturase)

Q40. Which substrate is the primer bound to the KS (ketoacyl synthase) active site at initiation of palmitate synthesis?

  • Malonyl‑ACP
  • Acetyl‑CoA (as acetyl‑KS or acetyl‑transfer)
  • Palmitoyl‑ACP
  • Acetoacetyl‑CoA

Correct Answer: Acetyl‑CoA (as acetyl‑KS or acetyl‑transfer)

Q41. A mutation that prevents ACP phosphopantetheinylation would most directly impair:

  • NADPH production
  • Acyl group tethering to ACP and chain elongation
  • Malonyl‑CoA synthesis by ACC
  • Carnitine shuttle function

Correct Answer: Acyl group tethering to ACP and chain elongation

Q42. Which enzyme activity is required to convert cytosolic oxaloacetate back to pyruvate while generating NADPH?

  • Malate dehydrogenase (cytosolic) only
  • Malic enzyme converting malate to pyruvate (ME1)
  • Pyruvate carboxylase
  • Isocitrate dehydrogenase (mitochondrial)

Correct Answer: Malic enzyme converting malate to pyruvate (ME1)

Q43. Which lipid product would you expect to decrease first after pharmacologic inhibition of ATP‑citrate lyase in the liver?

  • Cholesterol only
  • Cytosolic acetyl‑CoA derived lipids including fatty acids and cholesterol
  • Ketone bodies exclusively
  • Triglycerides in adipose only

Correct Answer: Cytosolic acetyl‑CoA derived lipids including fatty acids and cholesterol

Q44. Which of the following best describes the thermodynamic contribution of malonyl‑CoA decarboxylation to fatty acid elongation?

  • Decarboxylation is endergonic and consumes ATP
  • Decarboxylation releases CO2 and makes condensation exergonic
  • Decarboxylation generates NADPH for reduction
  • Decarboxylation removes a two‑carbon unit as CO2

Correct Answer: Decarboxylation releases CO2 and makes condensation exergonic

Q45. Which technique would best identify changes in expression of FAS protein in liver tissue?

  • RT‑PCR for mRNA only
  • Western blot for FAS protein
  • GC‑MS fatty acid profiling only
  • Enzyme histochemistry for ACC only

Correct Answer: Western blot for FAS protein

Q46. Which statement about palmitic acid is correct?

  • It is an essential polyunsaturated fatty acid
  • It is a 16‑carbon saturated fatty acid produced by FAS
  • It cannot be elongated or desaturated in cells
  • It directly inhibits ACC when present

Correct Answer: It is a 16‑carbon saturated fatty acid produced by FAS

Q47. In mammals, malonyl‑CoA for cytosolic fatty acid synthesis is synthesized by which cellular enzyme using ATP and bicarbonate?

  • Acyl‑CoA synthetase
  • Acetyl‑CoA carboxylase (ACC)
  • Pyruvate carboxylase
  • Citrate lyase

Correct Answer: Acetyl‑CoA carboxylase (ACC)

Q48. Which regulatory change would you expect after prolonged fasting to reduce hepatic lipogenesis?

  • Increased insulin and ACC activation
  • AMPK activation leading to ACC phosphorylation and inhibition
  • Upregulation of ATP‑citrate lyase activity
  • Increased citrate export from mitochondria

Correct Answer: AMPK activation leading to ACC phosphorylation and inhibition

Q49. Which fatty acid modification occurs in the endoplasmic reticulum and requires malonyl‑CoA and NADPH?

  • Fatty acid β‑oxidation
  • Elongation of long‑chain fatty acids (ELOVL enzymes)
  • De novo synthesis initiation
  • Glycerol backbone synthesis

Correct Answer: Elongation of long‑chain fatty acids (ELOVL enzymes)

Q50. Which best summarizes the overall stoichiometry for palmitate synthesis from acetyl‑CoA, ATP and NADPH?

  • 8 acetyl‑CoA + 7 ATP + 14 NADPH → palmitate + byproducts
  • 16 acetyl‑CoA + 14 ATP + 7 NADPH → palmitate
  • 4 acetyl‑CoA + 7 ATP + 14 NADPH → palmitate
  • 8 acetyl‑CoA + 14 ATP + 7 NADPH → palmitate

Correct Answer: 8 acetyl‑CoA + 7 ATP + 14 NADPH → palmitate + byproducts

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