Fatty Acid Synthesis
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- Where does de novo fatty acid synthesis occur?
- cytoplasm
- Where does elongation of existing fatty acids take place?
- mitochondria
- Where does desaturation of fatty acids occur?
- endoplasmic reticulum
- How does the Acetyl-CoA needed for fatty acid synthesis get from the mitochondria where it is formed to the cytoplasm?
- Acetyl CoA can't cross the mitochondrial membrane, but citrate can. Citrate is broken down into Acetyl-CoA and OAA by citrate lyase.
- What is the rate limiting step in de novo fatty acid synthesis?
- The conversion of Acetyl-CoA to malonyl CoA by Acetyl CoA carboxylase using 1 ATP, CO2 and a biotin cofactor.
- What reducing cofactor is used in de novo fatty acid synthesis? How is it's levels maintained in the cytoplasm?
- NADPH, Citrate -> OAA -> malate -> pyruvate + NADPH
- What inhibits Acetyl CoA carboxylase?
- palmitoyl CoA, phosphorylation by cAMP mediated protein kinases
- What stimulates Acetyl CoA carboxylase?
- citrate
- What is the effect of glucagon on fatty acid synthesis?
- inhibits fatty acid synthesis
- What is the effect of glucagon on beta oxidation? How?
- stimulates beta oxidation because it inhibits the formation of malonyl CoA which inhibits the carnitine palmitoyl transferase 1 needed for beta oxidation
- What enzymes are part of Fatty acid Synthetase complex (FAS)?
- acetyl transferase, malonyl transferase, beta-ketoacyl synthetase, beta-ketoacyl reductase, dehydratase, enoyl reductase
- What enzyme transfers acetyl CoA to the FAS complex?
- acetyl transferase
- What enzyme transfers malonyl CoA to the ACP-sulfhydryl on the FAS complex?
- malonyl transferase
- What is an ACP?
- acyl carrier protein
- What does beta-ketoacyl synthetase do?
- transfers the acetyl group on FAS to the alpha carbon of malonyl CoA on ACP displacing CO2
- What does beta-ketoacyl reductase do? What cofactor does it use?
- reduces the beta carbon producing beta hydroxybutyryl-S-ACP and oxidizing NADPH to NADP+
- What enzyme creates a double bond between the alpha and beta carbons of beta hydroxybutyryl-S-ACP?
- dehydratase
- What enzyme reduces the carbon double bond created by the dehydratase enzyme in fatty acid synthesis? Does it require a cofactor?
- Enoyl reductase, oxidizes NADPH to NADP+
- What is the last step in de novo fatty acid synthesis? What enzyme catalyzes it?
- a transferase shifts the newly formed acyl from the Sulfhydryl of ACP to the sulfhydryl of FAS, freeing it to accept another malonyl CoA molecule and continue elongation
- What is the longest fatty acid carbon chain that can be created by de novo fatty acid synthesis?
- Palmitic Acid (16:0)
- What does deacylase do?
- it removes the newly synthesised fatty acid from FAS so that FAS can be reused to synthesize more FAs
- How many CO2 are consumed to synthesize palmitic acid by de novo fatty acid synthesis?
- 7 CO2 (one for every malonyl CoA formed and added to the growing fatty acid)
- How many NADPH are consumed per malonyl CoA added to the fatty acid chain?
- 2 NADPH
- Which step of de novo fatty acid synthesis requires ATP?
- the formation of malonyl CoA from acetyl CoA via acetyl CoA carboxylase
- Name three pathways that generate NADPH.
- pentose phosphate pathway, isocitrate dehydrogenase, malic enzyme (malate -> pyruvate)
- Why does C75 Cerulenin drug inhibit hunger?
- it inhibits the fatty acid synthetase complex, thereby causing a buildup of malonyl CoA qhich either inhibits neuropeptide Y or other neuropeptides that stimulate hunger sensation in the brain
- fatty acid elongation in the mitochondria uses what precursor and adds what compound to it?
- starts with palmityl CoA and adds acetyl CoA
- Name the four enzymes involved in fatty acid elongation in order.
- thiolase, dehydrogenase, hydratase, dehydrogenase (reverse of beta oxidation pathway)
- the dehydrogenases in fatty acid elongation use what cofactor?
- NADPH (it gets oxidized)
- fatty acid elongation in the ER uses which compound as the 2 carbon donor?
- malonyl CoA
- What reaction does thiolase catalyze in fatty acid elongation?
- The transfer of palmitoyl CoA onto the alpha carbon of acetyl CoA.
- Under what conditions does fatty acid elongation occur?
- in the fed state
- why are linoleic and linolenic acids essential?
- because the mixed function oxidase used in the desaturation of fatty acids in the ER cannot add a double bond beyond the 9-10 carbons of fatty acids
- what enzyme adds double bonds to saturated fatty acids in the ER?
- mixed-function oxidase called desaturase
- does desaturase use a cofactor? which one?
- it oxidizes NADPH to NADP+
- what kind of double bond does desaturase create?
- cis
- what is the precursor of arachidonic acid?
- linoleic acid
- what is the precursor of docosahexaenoic acid?
- linolenic acid
- what pathway uses arachidonic acid as a substrate?
- prostaglandin synthesis
- what is docosahexaenoic acid used for?
- neuronal synapses and retinal photoreceptors