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

I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.
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