40 Questions
What is the primary function of ELOVL7 in fatty acid metabolism?
To elongate fatty acids through a condensation reaction
What is the byproduct of the condensation reaction in the ELOVL7 mechanism?
CO2
What type of enzymes are involved in the introduction of double bonds in fatty acids?
Acyl-CoA desaturases
What is the role of stearoyl-CoA desaturases (SCDs) in fatty acid metabolism?
To introduce double bonds at C9 of saturated fatty acids
Which fatty acid is a precursor for the synthesis of prostaglandins?
Arachidonic acid (20:4Δ5,8,11,14)
What is the function of fatty acid desaturases (FADS) in fatty acid metabolism?
To work on unsaturated fatty acids
What is the significance of Δ12 and Δ15-desaturases in fatty acid metabolism?
They are involved in the synthesis of omega-6 and omega-3 fatty acids
What is the mode of catalysis in the ELOVL7 mechanism?
Condensation followed by reduction and dehydration
What is the role of ferredoxin in the stearoyl-CoA desaturase reaction?
To donate a single electron to the Fe(II) center
What is the consequence of the reduced charges on the Fe ions in the stearoyl-CoA desaturase reaction?
The loss of the oxide bridging ion and its replacement with dioxygen
What is the role of water in the stearoyl-CoA desaturase reaction?
To coordinate with one of the Fe(II) centers, causing it to donate a single electron
What is the result of the first homolytic addition of the dioxygen molecule to both Fe(II) centers?
The elimination of a hydride ion
What is the function of the hydroxide on the first Fe(IV) center?
To deprotonate the stearoyl-[acyl-carrier protein] substrate
What is the result of the elimination of a hydride ion?
The regeneration of the enzyme
What is the role of the second Fe(IV) center in the stearoyl-CoA desaturase reaction?
To bind the hydroxide that attacks the stearoyl-[acyl-carrier protein] substrate
What is the overall function of the stearoyl-CoA desaturase enzyme?
To desaturate fatty acids
What is the result of the redox reactions involving oxygen, water, and iron centers in the Stearoyl-acyl-carrier protein desaturase mechanism?
Deprotonation of the substrate and formation of a double bond
What is the role of the Ser 92 and His 201 residues in the Malonyl-Palmitoyl Transferase (MPT)/Malonyl-CoA-acyl carrier protein transacylase (MAT) mechanism?
They are involved in an acylation/deacylation of the catalytic serine.
What is the difference between mitochondrial fatty acid synthesis and cytoplasmic fatty acid synthesis in terms of products?
Mitochondrial FAS produces 8:0, while cytoplasmic FAS produces 16:0
What is the role of malonyl-CoA in mitochondrial fatty acid synthesis?
It donates the two carbon units to the growing acyl-ACP chain
What is the function of the yeast enzyme in the fatty acid synthase cycle?
It is involved in the electron transfer reaction.
What is the product of the fatty acid synthase cycle?
16:0-SCoA
What is the purpose of ATP cleavage in mitochondrial fatty acid synthesis?
To drive the condensation process
What is the role of NADPH in the fatty acid synthase cycle?
It is involved in the electron transfer reaction.
What is the structural difference between octanoate and lipoic acid?
Octanoate has a COOH group, while lipoic acid has a SH group
What is the electron transport chain in Stearoyl-acyl-carrier protein desaturase mechanism?
A series of redox reactions involving oxygen, water, and iron centers
What is the function of Malonyl-Palmitoyl Transferase (MPT)/Malonyl-CoA-acyl carrier protein transacylase (MAT)?
It catalyzes the transfer of the acyl group to ACP.
What is the role of ACP in the fatty acid synthase cycle?
It carries the acyl group during the fatty acid elongation.
What is the role of the iron centers in the Stearoyl-acyl-carrier protein desaturase mechanism?
To facilitate the electron transport chain
What is the similarity between the electron transport chain in Stearoyl-acyl-carrier protein desaturase and E. coli ribonucleotide reductase protein R2?
Both have a similar electron transport chain mechanism
What is the product of the enzyme β-ketodehydratase?
b-enoylacyl-ACP
Where does the elongation of fatty acids occur in mammals?
Endoplasmic reticulum
What is the primary function of Stearoyl-CoA Desaturases (SCD1 and SCD2) in fatty acid synthesis?
Desaturation of fatty acids
What is the role of the tightly-bound FMN in the yeast enzyme?
It is involved in the electron transfer reaction.
What is the substrate used for the elongation of fatty acids in mammals?
Malonyl-CoA
Which enzyme is responsible for the synthesis of 16:0 fatty acid in mammals?
Fatty Acid Synthase
What is the role of ELOVL enzymes in fatty acid synthesis?
Elongation of fatty acids
Where does the synthesis of fatty acids occur in mammals?
Cytoplasm
What is the function of Acetyl-CoA Carboxylase in fatty acid synthesis?
Synthesis of malonyl-CoA
What is the byproduct of the elongation reaction in fatty acid synthesis?
CO2
Study Notes
Stearoyl-CoA Desaturase Reaction
- The reaction involves ferredoxin, a small iron-sulfur protein, donating a single electron to one of the Fe(III) centers in the desaturase
- This process is repeated, with ferredoxin donating a second single electron to the second Fe(III) center
- The reduced charges on the Fe ions lead to the loss of the oxide bridging ion (O2-) and its replacement with dioxygen
- Water coordinates to one of the Fe(II)s, causing it to donate a single electron to the dioxygen molecule
- This starts the first of two homolytic additions of the dioxygen molecule to both Fe(II) centers
- The second Fe(II) center also donates a single electron to the dioxygen bridge
Malonyl-Palmitoyl Transferase (MPT)/Malonyl-CoA-Acyl Carrier Protein Transacylase (MAT)
- Found in yeast (MPT) and human (MAT) domains
- Mechanism involves Arg 117, Gln 11, Leu 93, and Ser 92 residues
- Involves acylation/deacylation of the catalytic serine
β-Ketodehydratase Mechanism
- Involves residues Leu 885, Gly 888, Asp 1033, Tyr 1003, and His 1037
- Mechanism involves deprotonation of the stearoyl-[acyl-carrier protein] substrate, initiating the elimination of a hydride ion
- Excess electrons are donated singly to both Fe(IV) centers, regenerating the enzyme
Enoyl Reductase
- Last reaction in the fatty acid synthase cycle
- Yeast enzyme has a tightly-bound FMN involved in electron transfer (reduction) along with NADPH
- NADP+ and NADPH are involved in the electron transfer process
Fatty Acid Elongation and Desaturation
- Elongation occurs in the endoplasmic reticulum of mammals from 16:0 made through fatty acid synthase in the cytoplasm
- Elongation is carried out by a family of ELOngation of Very Long-chain fatty acid enzymes (ELOVLs)
- Desaturation is catalyzed by Stearoyl-CoA Desaturases (SCD1 and SCD2) and Fatty Acid Desaturases (FADS1 and FADS2)
Stearoyl-CoA Desaturase Mechanism
- Introduces a double bond at C9 of saturated fatty acid
- Involves electron transport chain carrying an electron from ferredoxin to one of the iron centers via several residues
- Second electron is then carried to the second iron center
- Redox reactions take place involving oxygen, water, and iron centers, resulting in the deprotonation of the substrate and the formation of a double bond
This quiz covers the mechanism of mammalian fatty acid elongase 7 (ELOVL7) and its interactive 3D model. It explores the condensation, reduction, and dehydration processes involved in fatty acid elongation.
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