Correct Answer: B. Palmitic acid
Palmitic acid (16:0, a saturated fatty acid with 16 carbons) is the primary and most common end-product of de novo fatty acid synthesis in humans. The fatty acid synthase (FAS) complex catalyzes sequential condensation, reduction, and dehydration cycles, adding 2-carbon units (from malonyl-CoA) to a growing chain. The enzyme releases the product once the chain reaches 16 carbons—this is the inherent termination point of mammalian FAS. Palmitic acid is then either incorporated into triglycerides, phospholipids, and cholesterol esters, or undergoes further elongation and desaturation to form longer-chain and unsaturated fatty acids. In the Indian population, dysregulation of fatty acid synthesis (driven by high carbohydrate intake and sedentary lifestyle) contributes significantly to the rising prevalence of metabolic syndrome, NAFLD, and type 2 diabetes. The synthesis occurs primarily in the liver and adipose tissue, making palmitic acid a critical hub in lipid metabolism and a key driver of hepatic steatosis when overproduced.
Why the other options are wrong
A. Acetyl CoA — Acetyl CoA is the substrate (building block) for fatty acid synthesis, not the end-product. It is first carboxylated to malonyl-CoA by acetyl-CoA carboxylase, then condensed iteratively by FAS. Confusing substrate with product is a classic NBE trap in lipid metabolism questions. C. Arachidonic acid — Arachidonic acid (20:4, an omega-6 polyunsaturated fatty acid) is NOT synthesized de novo in humans; it must be obtained from dietary sources (meat, eggs, dairy) or derived from linoleic acid via elongation and desaturation. It is a secondary product, not a primary end-product of FAS. D. Oleic acid — Oleic acid (18:1, a monounsaturated fatty acid) is derived from palmitic acid via further elongation (palmitate → stearate → oleate) and desaturation by Δ9-desaturase. It is a secondary product downstream of palmitate, not the direct end-product of the FAS enzyme complex.
High-Yield Facts
- Palmitic acid (16:0) is the direct, obligatory end-product released by mammalian fatty acid synthase; no longer-chain products are made de novo.
- Acetyl-CoA carboxylase catalyzes the rate-limiting step (acetyl-CoA → malonyl-CoA); insulin activates it, glucagon/AMP inhibit it—key regulatory node in fed vs. fasted state.
- Fatty acid synthase operates as a homodimer with a 4′-phosphopantetheine arm; each cycle adds 2 carbons and requires 2 NADPH, making it energy-intensive.
- Palmitate elongation to stearate (18:0) and subsequent Δ9-desaturation to oleate (18:1) occur in the endoplasmic reticulum, not during initial FAS synthesis.
- In NAFLD and metabolic syndrome (rising in India), excess palmitate accumulation drives hepatic triglyceride synthesis and lipotoxicity; FAS inhibitors are under investigation as therapeutic targets.
Mnemonics
FAS = 16 (Sixteen) Fatty Acid Synthase releases its product at 16 carbons (palmitate). Remember: FAS stops at 16, then elongase takes over. Use this when asked 'what does FAS make?' — always palmitate. PAL → STOLE → OLE Palmitate (PAL) → Stearate (STE) → Oleate (OLE). This chain shows the post-FAS modifications: elongation then desaturation. Helps distinguish the primary product (PAL) from secondary products.
NBE Trap
NBE often pairs "acetyl-CoA" with "fatty acid synthesis" to trap students who confuse the substrate with the product. Additionally, listing oleic acid (a common dietary and tissue fatty acid) as an option lures those who conflate "common in the body" with "product of de novo synthesis."
Clinical Pearl
In Indian patients with metabolic syndrome and NAFLD, excess carbohydrate intake drives acetyl-CoA carboxylase and FAS activity, flooding the liver with palmitate. This palmitate is rapidly esterified into triglycerides, causing hepatic steatosis and insulin resistance—a key pathogenic mechanism in the rising epidemic of type 2 diabetes in India.
_Reference: Harper's Illustrated Biochemistry, Ch. 23 (Lipid Synthesis & Transport); KD Tripathi Essentials of Medical Pharmacology, Ch. 32 (Lipid-Lowering Drugs)_