L12 - Fatty acid biosynthesis

Question 1

Fatty acids: why are they synthesised?

Answer 1

• Mammals have essentially an unlimited capacity to store them
• They are significantly better energy stores than glucose

Question 2

Fatty acids: what enzyme builds them up and where does this occur?

Answer 2

FAS - fatty acid synthase, building up occurs while it is attached, she said

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• Occurs in the cytosol in yeast/animal cells (ATP/NADH present here)
• In chloroplast in plant cells (ATP/NADPH is produced in chloroplast)

Question 3

Acetyl-CoA; what is it, where is it typically found, what does it do, and how does it move across membranes?

Answer 3

The molecule that is used to enter the citric acid cycle for energy production

Mitochondria

Key metabolic intermediate:
Either enter the TCA cycle for energy production or fatty acid biosynthesis

To move to the cytosol for fatty acid biosynthesis, it is converted to citrate and moved through a citrate transporter, and then converted back into acetyl-CoA

Question 4

ACC: what is it, what does it do, and what regulation does it have?

Answer 4

Acetyl-CoA carboxylase - an enzyme

Synthesises malonyl-CoA (O⁻O=C-CH₂CO-S-CoA) from acetyl-CoA (CH₃CO-S-CoA) using ATP and HCO₃⁻, H₂O is also produced

Local, global, fine, coarse, etc

Question 5

Fatty acid synthesis: the process

Answer 5

Acetyl-CoA converted to malonyl-CoA by ACC - irreversible ⇒ committed step

Watch leccy

Malonyl group transferred from CoA to FAS
Sequence of reactions (catalysed by the multiple active sites)
Adds 2 carbons onto growing FA chain
Repeated with second malonyl unit etc → FA chain
Each cycle uses 1 ATP (to produce malonyl-CoA) and 2 NADPH
Produces palmitate (16 carbons)

Question 6

Subcellular locations of fatty acid synthesis in animals and yeast cells: what are they and what do they do?

Answer 6

• Cytosol - NADPH production (pentose phosphate pathway), fatty acids synthesis, early isoprenoid/sterol synthesis
• Mitochondria - fatty acid oxidation, fatty acid elongation, ketone body synthesis, and acetyl CoA production
• Endoplasmic reticulum - Fatty acid elongation, fatty acid desaturation, phospholipid synthesis, late sterol synthesis

Question 7

Subcellular locations of fatty acid synthesis plant cells: what are they and what do they do?

Answer 7

• Chloroplast - NADPH production, fatty acids synthesis
• Peroxisome - fatty acid oxidation (little confusing, watch lecture?)
• Mitochondria - no fatty acid oxidation, acetyl CoA production
• Endoplasmic reticulum - fatty acid elongation, fatty acid desaturation, phospholipid synthesis, late sterol synthesis

Question 8

NADPH production

Answer 8

In animal/yeast cells, this occurs in the cytoplasm as a result of the pentose phosphate pathway (learn what this actually is)

In plant cells this occurs in chloroplasts

Question 9

NADPH vs NADH

Answer 9

NADH is mainly involved in catabolic reactions whereas NADPH is involved in anabolic reactions

Question 10

What is the regulatory point of fatty acid synthesis and what types of controls are there?

Answer 10

A-CoA carboxylase:

• Activity (fine control) - covalent modification, allostery, etc
• Quantity (coarse control) - transcription, translation, degradation, etc
• Global control (long-term coarse) - hormones influencing amounts
• Local control (fine) - citrate, AMP, fatty acids control

Question 11

What do insulin, glucagon, and epinephrine do to fat stores?

Answer 11

insulin - store fat (high blood glucose levels)
glucagon - use fat (low blood glucose levels)
epinephrine - use fat (high demand for energy)

Question 12

A-CoA carboxylase: what are its different forms and how is it (in)activated?

Answer 12

Active form - dephosphorylated by phosphatases using H₂O

Partially active form - (explained more in later flashcard)

inactive form - phosphorylated by kinases using ATP

Question 13

PKA: what is it, what is it activated by, and what does it do?

Answer 13

Protein kinase A

• Glucagon/epinephrine via cAMP production
• Low ATP
• High AMP

Inactivates ACC, stopping fatty acid production as the body needs energy to be used, not stored

Question 14

PP2A: what is it, how is it activated, and what does it do?

Answer 14

Protein phosphatase 2A

Insulin - low blood sugar levels

Inactivates ACC, causing fatty acid synthesis to be reduced

Question 15

AMPK: what is it, when is it activated, and what does it do?

Answer 15

AMP kinase

When AMP is high and ATP is low - low-energy

Inactivates ACC, causing fatty acid synthesis to be reduced

Question 16

How does ACC move between inactive and partially active forms?

Answer 16

Citrate - feedforward activation (signals that energy levels are high), polymerisation into longer chains (filament) which activate it

Palmitoyl-CoA - feedback inhibition (signals FA abundance), causes depolymerization into a less active dimer

Question 17

nearpod

Answer 17

leccy

Question 18

Palmitoyl production

Answer 18

Citrate -> Acetyl-CoA
Citrate lyase

Acetyl-CoA -> Malonyl-CoA
Acetyl-CoA carboxylase

Malonyl-CoA-> Palmitoyl-CoA

Question 19

FAS: where is it highly expressed?

Answer 19

FAS highly expressed in breast and prostate cancers

FAS inhibitor causes rapid weight loss

Anti-obesity drug that inhibits FAS also slows tumour growth

Therapeutic target for cancer and obesity

Question 20

Palmitate modification

Answer 20

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