GO:0005324 long-chain fatty acid transmembrane transporter activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0005324 describes the molecular function that enables the transfer of long-chain fatty acids (13 to 22 carbons) across a membrane [1,2].
• Key protein families include SLC27 (FATP1-6), CD36, and fatty acyl-CoA synthetases (ACSLs) that facilitate uptake and activation [2,6,7,8].
• CD36 (SR-B2) acts as a master regulator of cellular fatty acid homeostasis, influencing signaling and metabolic pathways.
• Dysregulation of long-chain fatty acid transport is linked to metabolic dysfunction-associated steatohepatitis (MASH), ferroptosis, and cancer [1,7].
• Protein S-acylation, a reversible lipid modification, depends on long-chain fatty acid metabolism and affects protein trafficking and function.
• L-carnitine is essential for mitochondrial long-chain fatty acid transport, highlighting the importance of this activity in energy metabolism.
Description
Long-chain fatty acid transmembrane transporter activity (GO:0005324) is a molecular function that enables the movement of fatty acids with aliphatic tails of 13 to 22 carbons across biological membranes [1,2]. This process is fundamental for cellular lipid uptake, energy production, and membrane synthesis. Researchers study this activity to understand how cells acquire fatty acids from the environment and how defects contribute to metabolic diseases [7,8]. The transport of long-chain fatty acids is not merely passive diffusion; it often requires specific membrane proteins and accessory enzymes that facilitate and regulate the process [2,6]. For example, fatty acyl-CoA synthetases such as FadD in Escherichia coli are required for the transmembrane movement and activation of exogenous long-chain fatty acids. In eukaryotes, proteins like CD36 and the SLC27 family (FATPs) are critical for fatty acid uptake and homeostasis [7,8]. Understanding GO:0005324 is therefore essential for dissecting lipid metabolism, signaling, and disease mechanisms.
long-chain fatty acid transmembrane transporter activity At A Glance
| GO ID | GO:0005324 |
|---|---|
| GO term | long-chain fatty acid transmembrane transporter activity |
| Ontology | molecular_function |
| Synonym | long-chain fatty acid transporter activity |
| Major function | Enables the transfer of long-chain fatty acids (13-22 carbons) across membranes |
| Related proteins | SLC27 family (FATP1-6), CD36, ACSL family, FadD |
| Associated processes | Fatty acid uptake, lipid homeostasis, energy metabolism, ferroptosis regulation |
| Disease relevance | MASH, cancer, metabolic disorders, ferroptosis-related pathologies |
What Is GO:0005324?
GO:0005324, long-chain fatty acid transmembrane transporter activity, is defined as the molecular function that enables the transfer of a long-chain fatty acid from one side of a membrane to the other. A long-chain fatty acid has an aliphatic tail containing 13 to 22 carbons. This activity is distinct from simple diffusion because it often involves specific transporter proteins that facilitate the movement of these hydrophobic molecules across lipid bilayers [1,2].
Why Is long-chain fatty acid transmembrane transporter activity Important in Cell Biology?
Long-chain fatty acid transmembrane transporter activity is crucial for maintaining cellular lipid homeostasis, providing substrates for energy production, membrane biogenesis, and signaling molecules. Dysregulation of this activity is implicated in a wide range of diseases, including metabolic dysfunction-associated steatohepatitis (MASH), cancer, and ferroptosis [1,7]. For instance, FATP5 deficiency alleviates MASH by remodeling hepatic lipid composition to suppress ferroptosis. Moreover, the SLC27 family of long-chain fatty acid transporters is emerging as a key player in human cancers, influencing tumor growth and progression. Therefore, understanding the molecular mechanisms and regulation of GO:0005324 is essential for developing therapeutic strategies targeting lipid metabolism.
• Provides essential fatty acids for energy production and membrane synthesis [2,4].
• Regulates cellular lipid homeostasis and signaling.
• Involved in the pathogenesis of metabolic diseases such as MASH.
• Plays a role in cancer development and progression through SLC27 transporters.
• Modulates ferroptosis, a form of regulated cell death, by affecting lipid composition.
• Required for protein S-acylation, a post-translational modification affecting protein function.
• Facilitates fatty acid uptake in plants and microorganisms, impacting agriculture and infection [5,6].
• Target for therapeutic intervention in obesity, diabetes, and cardiovascular diseases.
• Essential for mitochondrial fatty acid oxidation via carnitine shuttle.
• Influences immune cell function and inflammation through lipid signaling.
Mechanism, Genes and Research Methods
Biological Process: What Happens During long-chain fatty acid transmembrane transporter activity?
In simple terms: Long-chain fatty acids are moved across cell membranes with the help of specific proteins.
The biological process of long-chain fatty acid transmembrane transport involves the recognition, binding, and translocation of fatty acids across the lipid bilayer. In bacteria, fatty acyl-CoA synthetases such as FadD are required for the transmembrane movement and activation of exogenous long-chain fatty acids. In eukaryotes, this process is mediated by membrane proteins like CD36 and the SLC27 family (FATPs), which facilitate uptake into cells [7,8]. Once inside, fatty acids are activated to acyl-CoAs by ACSL enzymes and directed to various metabolic pathways, including beta-oxidation and lipid synthesis. This process is tightly regulated to maintain lipid homeostasis and respond to metabolic demands.
Cellular Component: Structure and Composition of long-chain fatty acid transmembrane transporter activity
In simple terms: The proteins that transport long-chain fatty acids are located in cell membranes and have specific structures.
The cellular components involved in long-chain fatty acid transmembrane transport include integral membrane proteins such as CD36, a scavenger receptor, and the SLC27 family of fatty acid transport proteins (FATP1-6) [7,8]. These proteins are embedded in the plasma membrane and possibly other organelle membranes. CD36 is a heavily glycosylated protein with two transmembrane domains and a large extracellular loop, facilitating fatty acid binding and uptake. SLC27 members are predicted to have multiple transmembrane domains and are expressed in various tissues, including liver, muscle, and adipose tissue. Additionally, fatty acyl-CoA synthetases like ACSL1 are associated with the membrane and may form complexes with transporters to channel fatty acids into metabolism.
Molecular Function: Molecular Mechanism of long-chain fatty acid transmembrane transporter activity
In simple terms: These transporter proteins bind long-chain fatty acids and help them cross the membrane.
The molecular mechanism of long-chain fatty acid transmembrane transport involves substrate binding, conformational changes, and release. CD36 binds long-chain fatty acids with high affinity and facilitates their diffusion across the membrane, possibly through a channel-like mechanism. SLC27 family members (FATPs) are thought to function as both transporters and enzymes, coupling fatty acid transport with acyl-CoA synthesis. In E. coli, FadD, a fatty acyl-CoA synthetase, is required for the transmembrane movement of exogenous long-chain fatty acids, indicating that activation is coupled to transport. The ATP/AMP signature motif of FadD is essential for enzyme activity and fatty acid transport. These mechanisms ensure efficient uptake and metabolic channeling of fatty acids.
Regulation of long-chain fatty acid transmembrane transporter activity
In simple terms: The activity of these transporters is controlled by various signals and conditions.
Long-chain fatty acid transmembrane transporter activity is regulated at multiple levels, including gene expression, post-translational modifications, and protein trafficking. CD36 expression is regulated by transcription factors such as PPARs and is subject to post-translational modifications, including palmitoylation and ubiquitination. Protein S-acylation, a reversible lipid modification, can affect the localization and function of transporters and signaling proteins. Hormones like insulin and leptin modulate fatty acid uptake by altering transporter localization. In addition, the availability of L-carnitine, which is required for mitochondrial long-chain fatty acid transport, influences overall fatty acid oxidation. Dysregulation of these regulatory mechanisms contributes to metabolic diseases [1,7].
Key Genes Involved in GO:0005324 long-chain fatty acid transmembrane transporter activity
The following genes and proteins are key players in long-chain fatty acid transmembrane transporter activity and related processes.
| Gene | Major Role | Research Relevance |
|---|---|---|
| CD36 | Master regulator of cellular fatty acid homeostasis; facilitates uptake of long-chain fatty acids | Implicated in metabolic diseases, cancer, and inflammation |
| SLC27A1 (FATP1) | Long-chain fatty acid transport protein; enhances fatty acid uptake and activation | Linked to obesity, insulin resistance, and cancer |
| SLC27A2 (FATP2) | Very long-chain acyl-CoA synthetase; involved in fatty acid transport and activation | Role in hepatic lipid metabolism and cancer |
| SLC27A3 (FATP3) | Fatty acid transport protein; may function in specific tissues | Emerging target in cancer and metabolic disorders |
| SLC27A4 (FATP4) | Major fatty acid transport protein in intestine; involved in lipid absorption | Associated with metabolic syndrome and cancer |
| SLC27A5 (FATP5) | Liver-specific fatty acid transport protein; involved in bile acid metabolism | Deficiency alleviates MASH via ferroptosis suppression |
| SLC27A6 (FATP6) | Heart-specific fatty acid transport protein; facilitates cardiac fatty acid uptake | Potential role in cardiac lipid metabolism |
| ACSL1 | Long-chain acyl-CoA synthetase 1; activates fatty acids for metabolism | Facilitates fatty acid uptake in yeast and mammals |
| ACSL2 | Long-chain acyl-CoA synthetase 2; involved in lipid synthesis | Plant and mammalian lipid metabolism |
| ACSL3 | Long-chain acyl-CoA synthetase 3; associated with lipid droplets | Role in cancer and lipid storage |
| FadD | Fatty acyl-CoA synthetase in E. coli; required for fatty acid transport and activation | Model for bacterial fatty acid uptake |
| LACS1 | Long-chain acyl-CoA synthetase 1 in Arabidopsis; facilitates fatty acid uptake | Plant lipid metabolism and stress responses |
| LACS2 | Long-chain acyl-CoA synthetase 2 in Arabidopsis; involved in cuticle formation | Plant development and defense |
| LACS3 | Long-chain acyl-CoA synthetase 3 in Arabidopsis; facilitates fatty acid uptake | Plant lipid metabolism |
| CPT1A | Carnitine palmitoyltransferase 1A; mitochondrial long-chain fatty acid transport | Requires L-carnitine for fatty acid oxidation |
| CPT2 | Carnitine palmitoyltransferase 2; inner mitochondrial membrane transport | Defects cause fatty acid oxidation disorders |
| SLC25A20 | Carnitine-acylcarnitine translocase; mitochondrial fatty acid transport | Mutations cause carnitine-acylcarnitine translocase deficiency |
How Is long-chain fatty acid transmembrane transporter activity Regulated?
Long-chain fatty acid transmembrane transporter activity is regulated at transcriptional, post-transcriptional, and post-translational levels. CD36 expression is controlled by nuclear receptors such as PPARγ and is modulated by insulin and leptin signaling. Protein S-acylation, a reversible lipid modification, can regulate the trafficking and function of CD36 and other membrane proteins. The SLC27 family members are regulated by metabolic status and hormones, affecting their localization and activity. Additionally, the availability of L-carnitine, which is required for mitochondrial long-chain fatty acid transport, influences overall fatty acid oxidation. Dysregulation of these regulatory pathways contributes to metabolic diseases such as MASH and cancer [1,7].
long-chain fatty acid transmembrane transporter activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| SLC27A5 (FATP5) | MASH, ferroptosis | Liver-specific knockout mouse, CRISPR KO in HepG2 cells |
| CD36 | Metabolic syndrome, atherosclerosis, cancer | CD36 knockout mice, overexpression in cell lines |
| SLC27A4 (FATP4) | Metabolic syndrome, intestinal lipid absorption | Intestinal-specific KO, organoids |
| ACSL1 | Insulin resistance, hepatic steatosis | Liver-specific KO, CRISPR KO in hepatocytes |
| CPT1A | Carnitine palmitoyltransferase I deficiency | Patient-derived fibroblasts, knock-in mouse models |
Metabolic Dysfunction-Associated Steatohepatitis (MASH)
FATP5 (SLC27A5) deficiency alleviates MASH by remodeling hepatic lipid composition to suppress ferroptosis. This highlights the critical role of long-chain fatty acid transport in liver disease pathogenesis. Dysregulated fatty acid uptake contributes to lipid accumulation, lipotoxicity, and inflammation in MASH.
Cancer
The SLC27 family of long-chain fatty acid transporters is implicated in human cancers, where they support tumor growth by supplying fatty acids for energy and membrane synthesis. CD36 also plays a role in cancer progression, mediating fatty acid uptake in tumor cells and influencing metastasis. Targeting these transporters is a potential therapeutic strategy.
Ferroptosis and Oxidative Stress
Long-chain fatty acid transport affects cellular lipid composition and susceptibility to ferroptosis, an iron-dependent form of cell death. FATP5 deficiency suppresses ferroptosis by altering hepatic lipid composition, suggesting that modulating fatty acid transport can influence oxidative stress and cell survival.
Cardiovascular and Metabolic Disorders
CD36 is a master regulator of fatty acid homeostasis and is involved in atherosclerosis, insulin resistance, and obesity. SLC27A6 (FATP6) is highly expressed in the heart and may contribute to cardiac lipid metabolism and disease. L-carnitine deficiency impairs mitochondrial long-chain fatty acid transport, leading to cardiomyopathy and metabolic decompensation.
From long-chain fatty acid transmembrane transporter activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of SLC27A5 affect hepatic lipid composition and ferroptosis? | Liver-specific SLC27A5 knockout mouse |
| What is the role of CD36 in fatty acid uptake in cancer cells? | CD36 knockout cancer cell lines (e.g., CRISPR-Cas9) |
| How does FATP4 contribute to intestinal fatty acid absorption? | Intestinal epithelial cell-specific FATP4 knockout mouse |
| Can point mutations in ACSL1 alter fatty acid transport activity? | CRISPR knock-in of point mutations in ACSL1 in cell lines |
| What is the effect of SLC27A1 overexpression on lipid accumulation? | Overexpression of SLC27A1 in adipocytes or hepatocytes |
| How does L-carnitine availability regulate mitochondrial fatty acid transport? | CPT1A knockout or knockdown cells supplemented with L-carnitine |
How to Study the long-chain fatty acid transmembrane transporter activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| CRISPR knockout screen | Genes required for fatty acid uptake | Identify novel transporters in cancer cells |
| Fluorescent fatty acid uptake assay | Rate of long-chain fatty acid transport | Assess CD36 or SLC27 function |
| Lipidomics (LC-MS) | Cellular lipid composition | Evaluate changes in lipid species upon transporter modulation |
| Metabolomics | Acyl-carnitine levels, fatty acid oxidation | Assess mitochondrial fatty acid transport |
| Proximity labeling (BioID) | Protein interactors of transporters | Map transport complex components |
| Co-immunoprecipitation | Physical interactions between proteins | Study ACSL-transporter complexes |
| RNA-seq | Gene expression changes | Identify transcriptional regulation of transporters |
| Western blot | Protein expression and modification | Validate knockout or overexpression |
CRISPR-Cas9 Knockout Screens
Genome-wide CRISPR knockout screens can identify genes required for long-chain fatty acid transmembrane transport. For example, knocking out SLC27 family members or CD36 can reveal their contribution to fatty acid uptake and cellular lipid levels [7,8]. These screens are typically performed in cell lines with a fluorescent fatty acid analog, followed by flow cytometry or sequencing to identify enriched sgRNAs.
Fluorescent Fatty Acid Uptake Assays
Fluorescently labeled long-chain fatty acids (e.g., BODIPY-palmitate) are used to measure transport activity in live cells. This method allows quantification of uptake kinetics and can be combined with CRISPR knockout or overexpression to study specific genes. It is widely used to assess the role of CD36 and SLC27 transporters [7,8].
Lipidomics and Metabolomics
Mass spectrometry-based lipidomics can profile cellular lipid composition to assess the impact of altered long-chain fatty acid transport. For instance, FATP5 deficiency remodels hepatic lipid composition, which can be detected by lipidomic analysis. Metabolomics can also measure acyl-carnitine levels to assess mitochondrial fatty acid oxidation.
Protein-Protein Interaction and Proximity Labeling
Proximity labeling techniques such as BioID or APEX can identify proteins interacting with long-chain fatty acid transporters like CD36 or FATPs. These methods help elucidate the transport complex and regulatory partners. Co-immunoprecipitation and mass spectrometry are also used to study interactions with ACSL enzymes.
How CRISPR Can Be Used to Study GO:0005324 long-chain fatty acid transmembrane transporter activity
Knockout
CRISPR-Cas9 knockout of genes encoding long-chain fatty acid transporters (e.g., SLC27A5, CD36) is used to study their role in fatty acid uptake and metabolism. For example, SLC27A5 knockout in liver cells can model MASH and ferroptosis resistance. Knockout of CD36 in cancer cell lines reduces fatty acid uptake and affects proliferation.
Point Mutation
Point mutations can be introduced into transporter genes to dissect functional domains. For instance, mutations in the ATP/AMP signature motif of FadD abolish fatty acid transport and enzyme activity. CRISPR knock-in of such mutations in mammalian cells can reveal critical residues for transport.
Knock-in
Knock-in of tagged versions of transporters (e.g., GFP or HA) allows visualization and biochemical analysis. This approach can be used to study the localization and trafficking of CD36 or SLC27 proteins. Knock-in of disease-associated mutations can model human disorders.
Overexpression
Overexpression of long-chain fatty acid transporters (e.g., SLC27A1, CD36) in cell lines increases fatty acid uptake and lipid accumulation, providing a gain-of-function model [7,8]. This is useful for studying the consequences of enhanced transport in metabolic diseases and cancer.
How EDITGENE Supports long-chain fatty acid transmembrane transporter activity Research
Researchers studying long-chain fatty acid transmembrane transporter activity-related genes often need to determine whether a candidate gene is causally involved in fatty acid uptake, lipid metabolism, or disease pathogenesis. EDITGENE provides comprehensive CRISPR gene editing services to create knockout, point-mutation, knock-in, and overexpression cell models, as well as CRISPR library screening and bioinformatics support, enabling precise functional studies of GO:0005324-related genes.
Contact EDITGENE today to design your custom CRISPR model for long-chain fatty acid transmembrane transporter activity research.
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FABP3 Knockout HEK293 Cell Line | EDJ-KQ1119 | Human | 2170 | Details Get a Quote |
| SLC2A1 Knockout HEK293 Cell Line | EDC08016 | Human | 6513 | Details Get a Quote |
| CD36 Knockout HEK293 Cell Line | EDJ-KQ1885 | Human | 948 | Details Get a Quote |
| ABCD3 Knockout HEK293 Cell Line | EDJ-KQ1905 | Human | 5825 | Details Get a Quote |
| UCP2 Knockout HEK293 Cell Line | EDJ-KQ2339 | Human | 7351 | Details Get a Quote |
| FABP1 Knockout HEK293 Cell Line | EDJ-KQ3052 | Human | 2168 | Details Get a Quote |
| SLC27A4 Knockout HEK293 Cell Line | EDJ-KQ3094 | Human | 10999 | Details Get a Quote |
| SLC27A1 Knockout HEK293 Cell Line | EDJ-KQ3543 | Human | 376497 | Details Get a Quote |
| FABP2 Knockout HEK293 Cell Line | EDJ-KQ3670 | Human | 2169 | Details Get a Quote |
| ABCD1 Knockout HEK293 Cell Line | EDC90269 | Human | 215 | Details Get a Quote |
| ABCD2 Knockout HEK293 Cell Line | EDJ-KQ4046 | Human | 225 | Details Get a Quote |
| ABCD4 Knockout HEK293 Cell Line | EDJ-KQ5612 | Human | 5826 | Details Get a Quote |
| SLC27A2 Knockout HEK293 Cell Line | EDJ-KQ6607 | Human | 11001 | Details Get a Quote |
| SLC27A5 Knockout HEK293 Cell Line | EDJ-KQ7238 | Human | 10998 | Details Get a Quote |
| SLC27A6 Knockout HEK293 Cell Line | EDJ-KQ8943 | Human | 28965 | Details Get a Quote |
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Frequently Asked Questions About long-chain fatty acid transmembrane transporter activity
What is long-chain fatty acid transmembrane transporter activity?
It is a molecular function (GO:0005324) that enables the transfer of long-chain fatty acids (13-22 carbons) across a membrane, often mediated by specific transporter proteins [1,2].
What genes are involved in long-chain fatty acid transmembrane transport?
Key genes include CD36, SLC27A1-6 (FATP1-6), ACSL1-3, and FadD in bacteria [2,6,7,8].
How is long-chain fatty acid transport regulated?
It is regulated by transcription factors (e.g., PPARs), post-translational modifications (e.g., S-acylation), and hormones like insulin [3,8].
What diseases are associated with defects in long-chain fatty acid transport?
Diseases include MASH, cancer, cardiovascular disorders, and ferroptosis-related pathologies [1,4,7,8].
What is the role of CD36 in fatty acid transport?
CD36 is a master regulator of cellular fatty acid homeostasis, facilitating uptake of long-chain fatty acids and influencing signaling and metabolism.
How can I study long-chain fatty acid transmembrane transporter activity?
Use fluorescent fatty acid uptake assays, CRISPR knockout screens, lipidomics, and metabolomics [1,7,8].
What is the SLC27 family?
SLC27 (solute carrier 27) family members, also known as FATPs, are long-chain fatty acid transport proteins involved in uptake and activation.
What is the role of ACSL enzymes in fatty acid transport?
ACSL enzymes activate long-chain fatty acids to acyl-CoAs, facilitating their transport and metabolism.
How does FATP5 deficiency affect MASH?
FATP5 deficiency alleviates MASH by remodeling hepatic lipid composition to suppress ferroptosis.
Can CRISPR be used to study long-chain fatty acid transporters?
Yes, CRISPR knockout, knock-in, and overexpression models are powerful tools to dissect gene function in fatty acid transport [1,7,8].
Conclusion
Long-chain fatty acid transmembrane transporter activity (GO:0005324) is a fundamental molecular function with critical roles in lipid metabolism, energy homeostasis, and disease. Key transporters such as CD36 and the SLC27 family, along with activating enzymes like ACSLs, orchestrate the uptake and utilization of long-chain fatty acids. Dysregulation of this activity contributes to MASH, cancer, and metabolic disorders, making it a promising therapeutic target. Advanced CRISPR-based models and screening technologies are essential for unraveling the complex regulation and function of these transporters. EDITGENE provides comprehensive services to support research on GO:0005324 and related pathways.
References
- 1. Liu Y et al.. 2025. FATP5 deficiency alleviates MASH via remodeling hepatic lipid composition to suppress ferroptosis.. Free Radic Biol Med 240:170-182 PMID: 40840619
- 2. Weimar JD et al.. 2002. Functional role of fatty acyl-coenzyme A synthetase in the transmembrane movement and activation of exogenous long-chain fatty acids. Amino acid residues within the ATP/AMP signature motif of Escherichia coli FadD are required for enzyme activity and fatty acid transport.. J Biol Chem 277(33):29369-76 PMID: 12034706
- 3. Chamberlain LH et al.. 2015. The physiology of protein S-acylation.. Physiol Rev 95(2):341-76 PMID: 25834228
- 4. Adeva-Andany MM et al.. 2017. Significance of l-carnitine for human health.. IUBMB Life 69(8):578-594 PMID: 28653367
- 6. Pulsifer IP et al.. 2012. Arabidopsis long-chain acyl-CoA synthetase 1 (LACS1), LACS2, and LACS3 facilitate fatty acid uptake in yeast.. Plant Physiol Biochem 51:31-9 PMID: 22153237
- 7. Xu Z et al.. 2026. SLC27, solute carrier 27 family, a long-chain fatty acid membrane transporters, in human cancers.. Front Cell Dev Biol 14:1839021 PMID: 42440857
- 8. Glatz JFC et al.. 2022. CD36 (SR-B2) as master regulator of cellular fatty acid homeostasis.. Curr Opin Lipidol 33(2):103-111 PMID: 35125400
