Do novo F.A synthesis

Flashcard 1 Q: What is the definition of de novo fatty acid synthesis, and where does it occur in the cell?

A: De novo fatty acid synthesis is the anabolic pathway that converts acetyl-CoA to long-chain saturated fatty acids (primarily palmitic acid, C16:0) via repetitive addition of two-carbon units. It occurs in the cytosol of cells (liver, adipose tissue, and lactating mammary glands).

Flashcard 2 Q: What are the physiological conditions and hormonal signals that activate fatty acid synthesis?

A: The fed state (high glucose → increased insulin) activates it. Insulin stimulates lipogenesis by increasing gene expression and activating acetyl-CoA carboxylase via dephosphorylation. Glucagon, adrenaline, and cortisol inhibit lipogenesis.

Flashcard 3 Q: List three key differences between fatty acid synthesis and β-oxidation.

A: 1) Location: Cytosol vs. mitochondrial matrix.

Coenzymes: NADPH vs. NAD⁺ and FAD.

Carrier: ACP vs. CoA.

Flashcard 4 Q: Write the complete reaction for the formation of acetyl-CoA from pyruvate, including the enzyme and coenzymes.

A: Pyruvate + CoA-SH + NAD⁺ → Acetyl-CoA + CO₂ + NADH + H⁺. Enzyme: Pyruvate dehydrogenase complex (PDC). Coenzymes: TPP, Lipoate, CoA-SH, FAD, NAD⁺.

Flashcard 5 Q: In which intracellular compartment does the pyruvate dehydrogenase complex function, and why is this important?

A: It functions in the mitochondrial matrix. This is important because the acetyl-CoA produced there cannot cross the inner mitochondrial membrane and must be transported to the cytosol via the citrate shuttle for fatty acid synthesis.

Flashcard 6 Q: What is the committing step of fatty acid synthesis? Write the complete reaction.

A: The carboxylation of acetyl-CoA to malonyl-CoA. Reaction: Acetyl-CoA + HCO₃⁻ + ATP → Malonyl-CoA + ADP + Pi.

Flashcard 7 Q: What is the full name and abbreviation of the enzyme that catalyzes the committing step, and what is its prosthetic group?

A: Enzyme: Acetyl-CoA carboxylase (ACC). Prosthetic group: Biotin (binds CO₂ as carboxybiotin intermediate).

Flashcard 8 Q: What metal ion is required for acetyl-CoA carboxylase activity, and what is the source of the carboxyl group?

A: Mg²⁺ or Mn²⁺ is required for ATP binding. The source of the carboxyl group is bicarbonate (HCO₃⁻).

Flashcard 9 Q: Describe the two-step mechanism of acetyl-CoA carboxylase.

A: Step 1: Biotin + ATP + HCO₃⁻ → Carboxybiotin + ADP + Pi (catalyzed by Biotin carboxylase domain). Step 2: Carboxybiotin + Acetyl-CoA → Malonyl-CoA + Biotin (catalyzed by Carboxyltransferase domain).

Flashcard 10 Q: How is acetyl-CoA carboxylase regulated allosterically and hormonally?

A: Allosteric: Activated by citrate; inhibited by palmitoyl-CoA. Hormonal: Activated by insulin (dephosphorylation); inhibited by glucagon and adrenaline (phosphorylation via AMPK/PKA).

Flashcard 11 Q: Describe the overall structure of the fatty acid synthase (FAS) complex in animals.

A: FAS is a homodimeric (α₂) complex. Each subunit is a multifunctional polypeptide (~270 kDa). The dimer is arranged in a head-to-tail orientation, forming an X-shaped structure.

Flashcard 12 Q: List all seven enzymatic domains of the animal FAS complex, their full names, and abbreviations.

A: KS – β-Ketoacyl-ACP synthase; AT – Acetyl/Malonyl-CoA transacylase; DH – Dehydratase; ER – Enoyl-ACP reductase; KR – β-Ketoacyl-ACP reductase; ACP – Acyl carrier protein; TE – Thioesterase.

Flashcard 13 Q: What is the role of the acyl carrier protein (ACP) domain and its phosphopantetheine prosthetic group?

A: The ACP domain acts as a "swinging arm" that carries the growing fatty acyl chain between catalytic domains. The phosphopantetheine group (derived from vitamin B₅) has a terminal thiol (-SH) that forms a high-energy thioester bond with the acyl chain, driving the elongation reactions.

Flashcard 14 Q: Write the initiation (priming) reaction for fatty acid synthesis.

A: Acetyl-CoA + ACP → Acetyl-ACP + CoA-SH. (Catalyzed by the AT domain).

Flashcard 15 Q: Write the reaction for loading malonyl-CoA onto the FAS complex.

A: Malonyl-CoA + ACP → Malonyl-ACP + CoA-SH. (Catalyzed by the AT domain).

Flashcard 16 Q: What are the four reactions of one elongation cycle in palmitic acid synthesis? Name the enzymes and coenzymes.

A: 1) Condensation (KS) – no coenzyme.

Reduction (KR) – NADPH.

Dehydration (DH) – no coenzyme.

Reduction (ER) – NADPH.

Flashcard 17 Q: Write the net reaction for the synthesis of palmitic acid from acetyl-CoA and malonyl-CoA.

A: Acetyl-CoA + 7 Malonyl-CoA + 14 NADPH + 14 H⁺ → Palmitic acid (C16:0) + 7 CO₂ + 14 NADP⁺ + 8 CoA-SH + 7 H₂O.

Flashcard 18 Q: How many cycles of elongation are required to synthesize palmitic acid (C16:0), and how does the chain grow?

A: 7 cycles are required. Each cycle adds 2 carbons from malonyl-CoA: C2 (acetyl) → C4 → C6 → C8 → C10 → C12 → C14 → C16.

Flashcard 19 Q: What terminates fatty acid synthesis, and which enzyme is responsible?

A: After 7 cycles, the completed palmitoyl-ACP (C16) is cleaved by thioesterase (TE): Palmitoyl-ACP + H₂O → Palmitic acid + ACP.

Flashcard 20 Q: What is the total ATP cost for synthesizing palmitic acid, and why?

A: 7 ATP are consumed. Each malonyl-CoA requires 1 ATP for its synthesis via acetyl-CoA carboxylase.

Flashcard 21 Q: Why is NADPH essential for fatty acid synthesis, and in which two steps is it used?

A: NADPH provides the reducing equivalents. It is used in the KR (β-ketoacyl-ACP reductase) and ER (enoyl-ACP reductase) steps of each elongation cycle.

Flashcard 22 Q: What are the two main pathways that generate cytosolic NADPH for lipogenesis?

A: 1) The pentose phosphate pathway (PPP) – oxidative phase.

The malic enzyme reaction (malate → pyruvate).

Flashcard 23 Q: Write the net reaction of the oxidative phase of the pentose phosphate pathway.

A: Glucose-6-phosphate + 2 NADP⁺ + H₂O → Ribulose-5-phosphate + 2 NADPH + 2 H⁺ + CO₂.

Flashcard 24 Q: List the three reactions of the oxidative phase of the PPP, including enzymes and coenzymes.

A: 1) G6P + NADP⁺ → 6-Phosphogluconolactone + NADPH (enzyme: G6PD).

6-Phosphogluconolactone + H₂O → 6-Phosphogluconate (enzyme: gluconolactonase).

6-Phosphogluconate + NADP⁺ → Ribulose-5-P + NADPH + CO₂ (enzyme: 6PGD).

Flashcard 25 Q: What is the rate-limiting enzyme of the pentose phosphate pathway, and how is it regulated?

A: Glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme. It is inhibited by high NADPH/NADP⁺ ratio via feedback inhibition.

Flashcard 26 Q: Write the reaction catalyzed by malic enzyme and explain its role in lipogenesis.

A: Malate + NADP⁺ → Pyruvate + NADPH + CO₂. It provides cytosolic NADPH and is part of the citrate shuttle for acetyl-CoA transport.

Flashcard 27 Q: How is acetyl-CoA transported from the mitochondria to the cytosol for fatty acid synthesis?

A: Via the citrate shuttle: Acetyl-CoA + OAA → Citrate (mitochondria) → citrate exits → cytosolic citrate → Acetyl-CoA + OAA (ATP-citrate lyase). OAA → Malate → Pyruvate (generating NADPH via malic enzyme).

Flashcard 28 Q: Why is fatty acid synthesis considered the reverse of β-oxidation? Give two structural differences.

A: It is essentially the reverse, but differs in:

Location: Cytosol vs. mitochondrial matrix.

Coenzymes: NADPH vs. NAD⁺/FAD.

Carrier: ACP vs. CoA.

Flashcard 29 Q: What is the role of the thioesterase (TE) domain, and what would happen if it were inhibited?

A: The TE domain releases the completed fatty acid (palmitic acid) from ACP. If inhibited, the fatty acid would remain attached to the FAS complex, preventing chain termination and product release.

Flashcard 30 Q: Compare the roles of insulin and glucagon in regulating fatty acid synthesis.

A: Insulin activates fatty acid synthesis by:

Increasing gene expression of lipogenic enzymes.

Activating ACC via dephosphorylation. Glucagon inhibits synthesis by:

Phosphorylating/inactivating ACC (via PKA).

Decreasing malonyl-CoA levels.