Long fatty acyl CoA synthetase
Encyclopedia
The Long chain fatty acyl-CoA synthetase enzyme
is a member of the ligase
family that activates the breakdown of complex fatty acids. Long chain fatty acyl-CoA synthetase plays a crucial role in intermediary metabolism
by catalyzing the formation of fatty acyl-CoA
by a two-step process proceeding through an adenylated
intermediate. It is an enzyme present in all organisms from bacteria to humans. It catalyzes the pre-step reaction for β-oxidation of fatty acids or can be incorporated in phospholipids.
Long chain fatty acyl-CoA synthetase, LC-FACS, plays a role in the physiological regulation of various cellular functions via the production of long chain fatty acyl-CoA esters, which reportedly have affected protein
transport, enzyme activation, protein acylation, cell signaling
, and transcriptional regulation. The formation of fatty acyl-CoA is catalyzed in two steps: a stable intermediate of fatty acyl-AMP molecule and then the product is formed—fatty acid acyl-CoA molecule.
Fatty acyl CoA synthetase catalyzes the activation of a long fatty acid chain to a fatty acyl CoA, requiring the energy of 1 ATP
to AMP
and pyrophosphate
. This step uses 2 "ATP equivalents" because pyrophosphate is cleaved into 2 molecules of inorganic phosphate, breaking a high-energy phosphate bond
.
In step one, ATP
and a long chain fatty acid
enter the enzyme’s active site
. Within the active site the negatively charged oxygen on the fatty acid attacks the alpha phosphate on ATP, forming an ATP-long chain fatty acid intermediate. (Step 1, Figure 3) In the second step, Pyrophosphate
(PPi) leaves, resulting in an AMP-long chain fatty acid molecule within the enzyme’s active site
. (Step 2, Figure 3) Coenzyme A
now enters the enzyme and another intermediate is formed which consists of AMP-long chain fatty acid-Coenzyme A. (Step 3, Figure 3) At the end of this mechanism two products are released, AMP and acyl coa synthetase. (Step 4, Figure 3)
Acyl CoA is formed from long chain fatty acids through an acyl substitution. In an ATP dependent reaction, the fatty acid carboxylate is converted to a thioester
. The final products of this reaction are acyl-CoA
, pyrophosphate
(PPi) and AMP
.
sequence similarity between the members of this superfamily. The enzymes in the family consist of a large N-terminal and a small C-terminal domain, with the catalytic site positioned between the two domains. Substrate binding may affect the relative positions of the C- and N-terminal domains. The C-terminal domain of LC-FACS is assumed to be in an open conformation when a substrate is absent and in a closed conformation when a substrate
is bound. The accessibility of the active site to solvent is reduced when the C- and N-terminal domains approach one another.
The structure-function relationship between LC-FACS and the formation and processing of the acyl-AMP intermediate was still unclear. A domain swapped dimer is formed by LC-FACS, with monomer
interacting at the N-terminal domains. A large electrostatically positive concave is located at the back of the structure in the central valley of the homodimer. Asp15 forms an intermolecular salt bridge with Arg176 in the dimer interactions. An intermolecular hydrogen bond is formed between the main chain carbonyl
group of Glu16and the side chain of Arg199. At the interface, Glu175 forms an intermolecular salt bridge with Arg199. The L motif, a six-amino acid peptide linker, connects the large N-terminal domain and a small C-terminal domain of each LC-FACS monomer. The N-terminal domain is composed of two subdomains: a distorted antiparallel β-barrel and two β-sheets surrounded by α-helices forming an αβαβα sandwich. The small C-terminal globular domain consists of two-stranded β-sheet and a three-stranded antiparallel β-sheet flanked by three α-helices.
between Asp15 of sequence A and Arg176 of sequence B. Figure 4 shows this salt bridge between these two amino acids. The yellow line between Asp15 and Arg176 shows the salt bridge present.
. AMP-PNP, a nonhydrolyzable ATP analogue, bound to LC-FACS results in the closed conformation with the C- and N-terminal domains directly interacting. In crystal structures, AMP-PNP is bound in a crevasse of each monomer at the interface between the N- and C-terminal domains. The closed conformation of the C-terminal domain is retained with myristroyl-AMP. Three residues in the C-terminal domain, Glu443, Glu475, and Lys527, interact noncovalently with L motif residues and the N-terminal domain to stabilize the closed conformation. There are two types of open conformations in the C-terminal domains of the uncomplexed structure. The C- and N-terminal domains do not interact directly for both monomers of the dimer. An extensive hydrogen bond network is used by the AMP moiety of the bound ATP molecule to hold the C- and N-terminal domains together.
of each monomer
. A large β-sheet and an α-helix cluster surround the tunnel which extends from the concave cavity in the central valley to the site of ATP-binding. There are two distinct paths in the large central pathway of the tunnel in the complex structure, which includes the “ATP path” and the “center path,” separated by the indole ring of Trp234 in the G motif. There is also another branch of the central pathway known as the “dead and branch.” The indole ring of Trp234 closes the fatty acid-binding tunnel in the uncomplexed structure. It opens up once AMP-PNP binds through hydrogen bond formation between β-phosphate and the nitrogen on the ring of Trp234. During this time, the closed conformation is adopted by the mobile C-terminal domain. There is a shift in the flexible loop of the G motif in the closed structures of LC-FACS, resulting in a wider dead end branch compared to the uncomplexed forms.
The ATP binding site is connected to an ATP path that is a hydrophobic channel in the fatty acid-binding tunnel. The fatty acid enters through the center path extending from the interface of the dimer along β-strand 13 to the ATP path. The connection between the two paths is blocked by the indole ring of Trp234 in the absence of ATP. Water molecules fill the center path in the AMP-PNP and myristoyl-AMP complex structures and through the entrance of the center path, they connect to the bulk solvent regions. The basic residues from each monomer, Lys219, Arg296, Arg297, Arg321, Lys350, and Lys 354, cause the entrance of the center path to generate a positive electrostatic potential. The dead end branch contains residues 235-243 and extends from the fatty acid-binding tunnel to α-helix h. The bottom of the dead end branch consists of a hydrophilic environment from the water molecules and polar side chains.
After searching 1v26 in Entrez, the location of the 5 domains was shown and was used to create figure 6 and 7. The ribbons colors in figure 6 correspond to the colors of the figure 7.
Free fatty acids inhibits the de novo fatty acid synthesis and appears to be dependent on the formation of long chain fatty acyl-CoAs. Studies have shown that long chain fatty acyl-CoAs inhibit ACC and FAS via feedback inhibition. Long chain fatty acyl-CoA’s inhibitory effect on the fatty acid synthesis may be a result of its regulation of lipogenic enzymes in a feedback manner through gene transcription suppression.
Long-chain fatty-acid-CoA ligase in cells catalytically synthesizes long chain fatty acyl-CoAs. Long-chain fatty-acid-CoA ligase may be involved in an important role in the suppression of fatty acid synthesis and it has been reported that it played a part in fatty acid synthesis inhibition. It was recently found that vitamin D3 upregulates FACL3, which forms long-chain fatty acid synthesis through the use of myristic acid
, eicosapentaenoic acid
(EPA), and arachidonic acid
as substrates, in expression and activity levels. FACL3 contributes to vitamin D3 growth inhibitory effect in human prostate cancer LNCaP cells. A current study reports that the feedback inhibition of FAS expression by long chain fatty acyl-CoAs causes the downregulation of FAS mRNA by vitamin D3.
, is the build up of long chain fatty acids in the brain and adrenal cortex, because of the decreased activity of long chain fatty acyl coa synthetase. The oxidation of the long chain fatty acids normally occurs in the peroxisome where the long chain fatty acyl coa synthetase is found. Long chain fatty acids enter the peroxisome via a transporter protein, ALDP, which creates a gate in the membrane of the peroxisome
. In ALD the gene for this peroximal membrane transporter, ALDP, is defective, preventing long chain fatty acids from entering the peroxisome.
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
is a member of the ligase
Ligase
In biochemistry, ligase is an enzyme that can catalyse the joining of two large molecules by forming a new chemical bond, usually with accompanying hydrolysis of a small chemical group dependent to one of the larger molecules...
family that activates the breakdown of complex fatty acids. Long chain fatty acyl-CoA synthetase plays a crucial role in intermediary metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
by catalyzing the formation of fatty acyl-CoA
Acyl-CoA
Acyl-CoA is a group of coenzymes involved in the metabolism of fatty acids. It is a temporary compound formed when coenzyme A attaches to the end of a long-chain fatty acid inside living cells. The compound undergoes beta oxidation, forming one or more molecules of acetyl-CoA...
by a two-step process proceeding through an adenylated
Adenylation
Adenylylation is a posttranslational modification that can occur to molecules such as tyrosine residues. Adenylylation involves a phosphodiester bond between a hydroxyl group of the molecule undergoing adenylylation and the phosphate group of the adenosine monophosphate nucleotide Adenylylation is...
intermediate. It is an enzyme present in all organisms from bacteria to humans. It catalyzes the pre-step reaction for β-oxidation of fatty acids or can be incorporated in phospholipids.
Long chain fatty acyl-CoA synthetase, LC-FACS, plays a role in the physiological regulation of various cellular functions via the production of long chain fatty acyl-CoA esters, which reportedly have affected protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
transport, enzyme activation, protein acylation, cell signaling
Cell signaling
Cell signaling is part of a complex system of communication that governs basic cellular activities and coordinates cell actions. The ability of cells to perceive and correctly respond to their microenvironment is the basis of development, tissue repair, and immunity as well as normal tissue...
, and transcriptional regulation. The formation of fatty acyl-CoA is catalyzed in two steps: a stable intermediate of fatty acyl-AMP molecule and then the product is formed—fatty acid acyl-CoA molecule.
Fatty acyl CoA synthetase catalyzes the activation of a long fatty acid chain to a fatty acyl CoA, requiring the energy of 1 ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
to AMP
Adenosine monophosphate
Adenosine monophosphate , also known as 5'-adenylic acid, is a nucleotide that is used as a monomer in RNA. It is an ester of phosphoric acid and the nucleoside adenosine. AMP consists of a phosphate group, the sugar ribose, and the nucleobase adenine...
and pyrophosphate
Pyrophosphate
In chemistry, the anion, the salts, and the esters of pyrophosphoric acid are called pyrophosphates. Any salt or ester containing two phosphate groups is called a diphosphate. As a food additive, diphosphates are known as E450.- Chemistry :...
. This step uses 2 "ATP equivalents" because pyrophosphate is cleaved into 2 molecules of inorganic phosphate, breaking a high-energy phosphate bond
Chemical bond
A chemical bond is an attraction between atoms that allows the formation of chemical substances that contain two or more atoms. The bond is caused by the electromagnetic force attraction between opposite charges, either between electrons and nuclei, or as the result of a dipole attraction...
.
Mechanism and active site
The mechanism for Long Chain Fatty Acyl-CoA Synthetase is a “bi uni uni bi ping-pong” mechanism. The uni and bi prefixes refer to the number of substrates that enter the enzyme and the number of products that leave the enzyme; bi describes a situation where two substrates enter the enzyme at the same. Ping-pong signifies that a product is released before another substrate can bind to the enzyme.In step one, ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
and a long chain fatty acid
Fatty acid
In chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from...
enter the enzyme’s active site
Active site
In biology the active site is part of an enzyme where substrates bind and undergo a chemical reaction. The majority of enzymes are proteins but RNA enzymes called ribozymes also exist. The active site of an enzyme is usually found in a cleft or pocket that is lined by amino acid residues that...
. Within the active site the negatively charged oxygen on the fatty acid attacks the alpha phosphate on ATP, forming an ATP-long chain fatty acid intermediate. (Step 1, Figure 3) In the second step, Pyrophosphate
Pyrophosphate
In chemistry, the anion, the salts, and the esters of pyrophosphoric acid are called pyrophosphates. Any salt or ester containing two phosphate groups is called a diphosphate. As a food additive, diphosphates are known as E450.- Chemistry :...
(PPi) leaves, resulting in an AMP-long chain fatty acid molecule within the enzyme’s active site
Active site
In biology the active site is part of an enzyme where substrates bind and undergo a chemical reaction. The majority of enzymes are proteins but RNA enzymes called ribozymes also exist. The active site of an enzyme is usually found in a cleft or pocket that is lined by amino acid residues that...
. (Step 2, Figure 3) Coenzyme A
Coenzyme A
Coenzyme A is a coenzyme, notable for its role in the synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle. All sequenced genomes encode enzymes that use coenzyme A as a substrate, and around 4% of cellular enzymes use it as a substrate...
now enters the enzyme and another intermediate is formed which consists of AMP-long chain fatty acid-Coenzyme A. (Step 3, Figure 3) At the end of this mechanism two products are released, AMP and acyl coa synthetase. (Step 4, Figure 3)
Acyl CoA is formed from long chain fatty acids through an acyl substitution. In an ATP dependent reaction, the fatty acid carboxylate is converted to a thioester
Thioester
Thioesters are compounds with the functional group C-S-CO-C. They are the product of esterification between a carboxylic acid and a thiol. Thioesters are widespread in biochemistry, the best-known derivative being acetyl-CoA.-Synthesis:...
. The final products of this reaction are acyl-CoA
Acyl-CoA
Acyl-CoA is a group of coenzymes involved in the metabolism of fatty acids. It is a temporary compound formed when coenzyme A attaches to the end of a long-chain fatty acid inside living cells. The compound undergoes beta oxidation, forming one or more molecules of acetyl-CoA...
, pyrophosphate
Pyrophosphate
In chemistry, the anion, the salts, and the esters of pyrophosphoric acid are called pyrophosphates. Any salt or ester containing two phosphate groups is called a diphosphate. As a food additive, diphosphates are known as E450.- Chemistry :...
(PPi) and AMP
Adenosine monophosphate
Adenosine monophosphate , also known as 5'-adenylic acid, is a nucleotide that is used as a monomer in RNA. It is an ester of phosphoric acid and the nucleoside adenosine. AMP consists of a phosphate group, the sugar ribose, and the nucleobase adenine...
.
Structure
There are several highly conserved areas and a 20-30% amino acidAmino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
sequence similarity between the members of this superfamily. The enzymes in the family consist of a large N-terminal and a small C-terminal domain, with the catalytic site positioned between the two domains. Substrate binding may affect the relative positions of the C- and N-terminal domains. The C-terminal domain of LC-FACS is assumed to be in an open conformation when a substrate is absent and in a closed conformation when a substrate
Substrate (biochemistry)
In biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate. In the case of a single substrate, the substrate binds with the enzyme active site, and an enzyme-substrate complex is formed. The substrate is transformed into one or...
is bound. The accessibility of the active site to solvent is reduced when the C- and N-terminal domains approach one another.
The structure-function relationship between LC-FACS and the formation and processing of the acyl-AMP intermediate was still unclear. A domain swapped dimer is formed by LC-FACS, with monomer
Monomer
A monomer is an atom or a small molecule that may bind chemically to other monomers to form a polymer; the term "monomeric protein" may also be used to describe one of the proteins making up a multiprotein complex...
interacting at the N-terminal domains. A large electrostatically positive concave is located at the back of the structure in the central valley of the homodimer. Asp15 forms an intermolecular salt bridge with Arg176 in the dimer interactions. An intermolecular hydrogen bond is formed between the main chain carbonyl
Carbonyl
In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups....
group of Glu16and the side chain of Arg199. At the interface, Glu175 forms an intermolecular salt bridge with Arg199. The L motif, a six-amino acid peptide linker, connects the large N-terminal domain and a small C-terminal domain of each LC-FACS monomer. The N-terminal domain is composed of two subdomains: a distorted antiparallel β-barrel and two β-sheets surrounded by α-helices forming an αβαβα sandwich. The small C-terminal globular domain consists of two-stranded β-sheet and a three-stranded antiparallel β-sheet flanked by three α-helices.
Dimer interaction
The dimerization of LC-FACS is stabilized through a salt bridgeSalt bridge
A salt bridge, in chemistry, is a laboratory device used to connect the oxidation and reduction half-cells of a galvanic cell , a type of electrochemical cell...
between Asp15 of sequence A and Arg176 of sequence B. Figure 4 shows this salt bridge between these two amino acids. The yellow line between Asp15 and Arg176 shows the salt bridge present.
ATP binding to the C-terminal domain
The conformations of the C-teriminal domain of the LC-FACS structures are dependent on the presence of a ligandLigand
In coordination chemistry, a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from...
. AMP-PNP, a nonhydrolyzable ATP analogue, bound to LC-FACS results in the closed conformation with the C- and N-terminal domains directly interacting. In crystal structures, AMP-PNP is bound in a crevasse of each monomer at the interface between the N- and C-terminal domains. The closed conformation of the C-terminal domain is retained with myristroyl-AMP. Three residues in the C-terminal domain, Glu443, Glu475, and Lys527, interact noncovalently with L motif residues and the N-terminal domain to stabilize the closed conformation. There are two types of open conformations in the C-terminal domains of the uncomplexed structure. The C- and N-terminal domains do not interact directly for both monomers of the dimer. An extensive hydrogen bond network is used by the AMP moiety of the bound ATP molecule to hold the C- and N-terminal domains together.
Fatty acid-binding tunnel
Bulkier long chain fatty acids are bound by a fatty acid-binding tunnel that is located in the N-terminal domainProtein domain
A protein domain is a part of protein sequence and structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded. Many proteins consist of several structural...
of each monomer
Monomer
A monomer is an atom or a small molecule that may bind chemically to other monomers to form a polymer; the term "monomeric protein" may also be used to describe one of the proteins making up a multiprotein complex...
. A large β-sheet and an α-helix cluster surround the tunnel which extends from the concave cavity in the central valley to the site of ATP-binding. There are two distinct paths in the large central pathway of the tunnel in the complex structure, which includes the “ATP path” and the “center path,” separated by the indole ring of Trp234 in the G motif. There is also another branch of the central pathway known as the “dead and branch.” The indole ring of Trp234 closes the fatty acid-binding tunnel in the uncomplexed structure. It opens up once AMP-PNP binds through hydrogen bond formation between β-phosphate and the nitrogen on the ring of Trp234. During this time, the closed conformation is adopted by the mobile C-terminal domain. There is a shift in the flexible loop of the G motif in the closed structures of LC-FACS, resulting in a wider dead end branch compared to the uncomplexed forms.
The ATP binding site is connected to an ATP path that is a hydrophobic channel in the fatty acid-binding tunnel. The fatty acid enters through the center path extending from the interface of the dimer along β-strand 13 to the ATP path. The connection between the two paths is blocked by the indole ring of Trp234 in the absence of ATP. Water molecules fill the center path in the AMP-PNP and myristoyl-AMP complex structures and through the entrance of the center path, they connect to the bulk solvent regions. The basic residues from each monomer, Lys219, Arg296, Arg297, Arg321, Lys350, and Lys 354, cause the entrance of the center path to generate a positive electrostatic potential. The dead end branch contains residues 235-243 and extends from the fatty acid-binding tunnel to α-helix h. The bottom of the dead end branch consists of a hydrophilic environment from the water molecules and polar side chains.
Domains
The domains founds in Long chain fatty acyl CoA synthetase are shown both in the enzyme view (figure 6) and sequence view (figure 7). LC-FACS has five domains.After searching 1v26 in Entrez, the location of the 5 domains was shown and was used to create figure 6 and 7. The ribbons colors in figure 6 correspond to the colors of the figure 7.
Inhibition by long chain fatty acyl-CoAs
A long term and short term regulation controls fatty acid synthesis. Long term fatty acid synthesis regulation is dependent on the rate of acetyl-CoA carboxylase (ACC) synthesis, the rate-limiting enzyme and first enzyme of the fatty acid synthesis, and fatty acid synthase (FAS), the second and major enzyme of the fatty acid synthesis. Cellular fatty acyl-CoA is involved in the short term regulation, but there is not a full understanding of the mechanisms.Free fatty acids inhibits the de novo fatty acid synthesis and appears to be dependent on the formation of long chain fatty acyl-CoAs. Studies have shown that long chain fatty acyl-CoAs inhibit ACC and FAS via feedback inhibition. Long chain fatty acyl-CoA’s inhibitory effect on the fatty acid synthesis may be a result of its regulation of lipogenic enzymes in a feedback manner through gene transcription suppression.
Long-chain fatty-acid-CoA ligase in cells catalytically synthesizes long chain fatty acyl-CoAs. Long-chain fatty-acid-CoA ligase may be involved in an important role in the suppression of fatty acid synthesis and it has been reported that it played a part in fatty acid synthesis inhibition. It was recently found that vitamin D3 upregulates FACL3, which forms long-chain fatty acid synthesis through the use of myristic acid
Myristic acid
Myristic acid, also called tetradecanoic acid, is a common saturated fatty acid with the molecular formula CH312COOH. A myristate is a salt or ester of myristic acid....
, eicosapentaenoic acid
Eicosapentaenoic acid
Eicosapentaenoic acid is an omega-3 fatty acid. In physiological literature, it is given the name 20:5. It also has the trivial name timnodonic acid...
(EPA), and arachidonic acid
Arachidonic acid
Arachidonic acid is a polyunsaturated omega-6 fatty acid 20:4.It is the counterpart to the saturated arachidic acid found in peanut oil, Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6).It is the counterpart to the saturated arachidic acid found in peanut oil,...
as substrates, in expression and activity levels. FACL3 contributes to vitamin D3 growth inhibitory effect in human prostate cancer LNCaP cells. A current study reports that the feedback inhibition of FAS expression by long chain fatty acyl-CoAs causes the downregulation of FAS mRNA by vitamin D3.
Diseases
Adrenoleukodystrophy (ALD)Adrenoleukodystrophy
Adrenoleukodystrophy is a rare, inherited disorder that leads to progressive brain damage, failure of the adrenal glands and eventually death. ALD is a disease in a group of genetic disorders called leukodystrophies, whose chief feature is damage to myelin...
, is the build up of long chain fatty acids in the brain and adrenal cortex, because of the decreased activity of long chain fatty acyl coa synthetase. The oxidation of the long chain fatty acids normally occurs in the peroxisome where the long chain fatty acyl coa synthetase is found. Long chain fatty acids enter the peroxisome via a transporter protein, ALDP, which creates a gate in the membrane of the peroxisome
Peroxisome
Peroxisomes are organelles found in virtually all eukaryotic cells. They are involved in the catabolism of very long chain fatty acids, branched chain fatty acids, D-amino acids, polyamines, and biosynthesis of plasmalogens, etherphospholipids critical for the normal function of mammalian brains...
. In ALD the gene for this peroximal membrane transporter, ALDP, is defective, preventing long chain fatty acids from entering the peroxisome.
Examples
Human genes encoding long-chain-fatty-acid—CoA ligase enzymes include:- ACSL1ACSL1Long-chain-fatty-acid—CoA ligase 1 is an enzyme that in humans is encoded by the ACSL1 gene.-Further reading:...
- ACSL3ACSL3Long-chain-fatty-acid—CoA ligase 3 is an enzyme that in humans is encoded by the ACSL3 gene.-Further reading:...
- ACSL4ACSL4Long-chain-fatty-acid—CoA ligase 4 is an enzyme that in humans is encoded by the ACSL4 gene.-Further reading:...
- ACSL5ACSL5Long-chain-fatty-acid—CoA ligase 5 is an enzyme that in humans is encoded by the ACSL5 gene.-Further reading:...
- ACSL6ACSL6Acyl-CoA synthetase long-chain family member 6 is an enzyme that in humans is encoded by the ACSL6 gene. Long-chain acyl-CoA synthetases such as ACSL6, catalyze the formation of acyl-CoA from fatty acids, ATP, and CoA....
- SLC27A2SLC27A2Very long-chain acyl-CoA synthetase is an enzyme that in humans is encoded by the SLC27A2 gene.-Further reading:...
See also
- Fatty acyl-CoA synthaseFatty-acyl-CoA synthaseIn enzymology, a fatty-acyl-CoA synthase is an enzyme that catalyzes the chemical reactionThe 5 substrates of this enzyme are acetyl-CoA, malonyl-CoA, NADH, NADPH, and H+, whereas its 5 products are long-chain-acyl-CoA, CoA, CO2, NAD+, and NADP+....
- Triacsin CTriacsin CTriacsin C is a potent inhibitor of long fatty acyl CoA synthetase. It blocks β-cell apoptosis, induced by fatty acids in a rat model of obesity...
- an inhibitor of Fatty acyl CoA synthetase