Fatty acid metabolism Flashcards
(19 cards)
How is fat mobilised from adipose tissue? (hormones, enzymes)
Mobilisation of Fat (TAGs) from Adipose Tissue
TAG = Triacylglycerol (a fat molecule made of 3 fatty acids + 1 glycerol).
Hormones (like glucagon, epinephrine, and cortisol) trigger lipolysis – fat breakdown.
Hormone-Sensitive Lipase (HSL) breaks down TAG into:
3 Free Fatty Acids (FFA) – go into the blood (bound to albumin).
1 Glycerol – goes to the liver for gluconeogenesis or glycolysis.
How are fatty acids activated?
Free fatty acids (FFA) must be activated before being burned for energy.
This happens in the cytoplasm:
Fatty Acyl-CoA Synthetase (FACS) catalyzes:
FFA + CoA + ATP → Fatty acyl-CoA (activated) + AMP + PPi
Thioester bond is formed (high energy).
Hydrolysis of pyrophosphate (PPi) makes this step irreversible.
What is beta-oxidation: how are fatty acids burned? (enzymes, steps, what does each round yield)
Occurs in the mitochondria and breaks fatty acids into acetyl-CoA, which goes into the TCA cycle.
Enzymes & Steps (for saturated even-chain FA):
Acyl-CoA Dehydrogenase – introduces a double bond at the β-carbon.
Enoyl-CoA Hydratase – adds water across the double bond (only L-isomer).
L-3-Hydroxyacyl-CoA Dehydrogenase – oxidizes OH to a keto group.
Beta-Ketothiolase – splits the ketoacyl into acetyl-CoA + shortened FA.
🔸Each round yields:
1 NADH
1 FADH₂
1 Acetyl-CoA
🔸Complete oxidation of palmitate (C16) → ~129 ATP!
What are the 2 special cases in fatty acid oxidation?
- unsaturated fatty acids
- odd chain fatty acids
How is unsaturated fatty acids special?
Need 2 additional enzymes to handle double bonds (not listed, but involve isomerases and reductases).
How are odd chain fatty acids special and what are the 3 enzymes used?
Final product is Propionyl-CoA, not acetyl-CoA.
Converted to Succinyl-CoA (enters TCA):
Propionyl-CoA Carboxylase (biotin)
Methylmalonyl-CoA Epimerase
Methylmalonyl-CoA Mutase (uses Vitamin B12)
Why can’t fats make glucose?
The link reaction (pyruvate → acetyl-CoA) is irreversible, so fats can’t contribute to net glucose.
How can ketones be used as an alternative fuel? (main types, used by?)
Produced in liver mitochondria from excess acetyl-CoA (when carbs are low, e.g., fasting).
Main types: Acetoacetate, Beta-hydroxybutyrate, Acetone
Used by:
Brain (especially during starvation – up to 75% of its energy)
Other tissues when glucose is scarce
What is the main enzyme for breaking down ketones?
Beta-hydroxybutyrate dehydrogenase: converts between acetoacetate and beta-hydroxybutyrate based on NAD+/NADH ratio
Where does fatty acid synthesis occur? What are the 2 key steps?Occurs in cytoplasm (opposite location to oxidation).
Occurs in cytoplasm (opposite location to oxidation).
🔁 Transport:
Acetyl-CoA (made in mitochondria) can’t directly cross into cytoplasm.
A shuttle system involving citrate is used.
🔨 Key Steps:
Acetyl-CoA Carboxylase:
Converts acetyl-CoA → malonyl-CoA
Committed & regulated step
Requires ATP
Fatty Acid Synthase (FAS):
Large enzyme complex with multiple activities on one polypeptide.
Uses Acyl Carrier Protein (ACP) instead of CoA.
What does ACP do?
Carries intermediates (like a mobile arm).
What does acetyl transacylase do?
Attaches acetyl to ACP.
What does malonyl transacylase do?
Attaches malonyl to ACP.
What does Acyl-malonyl ACP condensing enzyme do?
Condensation reaction → forms acetoacetyl-ACP (4C)
Powered by decarboxylation of malonyl group.
What does B-betoacyl ACP reductase do?
Reduces ketone to OH using NADPH
What does 3-Hydroxylacyl ACP dehydratase do?
Removes water (forms double bond)
What does ACP reductase do?
Reduces double bond → saturated chain
Inhibited by triclosan (antibacterial)
Repeats until 16C palmitate is formed
How are lipids transported? What are the 4 types?
Fatty acids (FFAs) → transported bound to serum albumin.
TAGs (from diet or liver) → transported in lipoproteins:
Chylomicrons – from gut
VLDL – from liver
LDL – delivers cholesterol
HDL – reverse cholesterol transport (“good cholesterol”)
