GO:0034625 fatty acid elongation, monounsaturated fatty acid: Pathway, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0034625 describes the elongation of a fatty acid chain into which one C-C double bond has already been introduced, producing monounsaturated fatty acids.
• ELOVL6 is the principal elongase that converts C16:0 and C16:1 into C18:0 and C18:1, and its activity influences membrane lipid composition and cellular fate.
• Monounsaturated fatty acid elongation is relevant to remyelination, cancer plasticity, chronic liver disease, and intramuscular fat deposition.
• The pathway is regulated by substrate availability, desaturase activity, and transcriptional programs such as Zeb1-mediated lipogenic enzyme expression.
• Gut microbiota and dietary factors can promote hepatic fatty acid desaturation and elongation, linking this GO term to host-microbe metabolic interactions.
• CRISPR knockout, point mutation, knock-in, and overexpression models enable causal dissection of ELOVL6 and related genes in this pathway.
Description
GO:0034625, fatty acid elongation, monounsaturated fatty acid, is a biological process that extends a fatty acid chain after a single C-C double bond has been introduced, yielding monounsaturated fatty acids with longer carbon chains. This process is distinct from saturated fatty acid elongation because the substrate already contains one double bond, and it is central to the synthesis of membrane phospholipids and storage lipids. Researchers study this term to understand how cells adjust lipid composition in response to metabolic, inflammatory, and oncogenic signals. The elongation step is catalyzed by membrane-bound enzymes of the ELOVL family, with ELOVL6 being a well-characterized enzyme that preferentially elongates C16:1 to C18:1. Because monounsaturated fatty acids are major components of cellular membranes and lipid droplets, their elongation affects membrane fluidity, signaling, and energy storage. Dysregulation of this pathway has been linked to impaired remyelination, cancer cell plasticity, and chronic liver disease, making it a target for mechanistic and translational studies.
fatty acid elongation, monounsaturated fatty acid At A Glance
| GO ID | GO:0034625 |
|---|---|
| GO term | fatty acid elongation, monounsaturated fatty acid |
| Ontology | biological_process |
| Synonym | none |
| Major function | Elongation of a fatty acid chain into which one C-C double bond has been introduced |
| Related enzymes | ELOVL family elongases, particularly ELOVL6 |
| Substrates | Monounsaturated fatty acyl-CoAs such as C16:1 |
| Products | Longer monounsaturated fatty acids such as C18:1 |
| Cellular location | Endoplasmic reticulum membrane |
| Associated processes | Lipid metabolism, membrane biogenesis, remyelination, cancer plasticity |
What Is GO:0034625?
In our own words, GO:0034625 refers to the biochemical elongation of a fatty acid chain that already contains one carbon-carbon double bond. The process adds two-carbon units to the carboxyl end of the monounsaturated fatty acid, producing a longer monounsaturated fatty acid. This is a subprocess of fatty acid elongation and is distinct from the elongation of saturated fatty acids or polyunsaturated fatty acids.
Why Is fatty acid elongation, monounsaturated fatty acid Important in Cell Biology?
GO:0034625 is important because monounsaturated fatty acid elongation directly influences the lipid composition of membranes and lipid droplets, which in turn affects cell signaling, inflammatory responses, and metabolic homeostasis. In the nervous system, ELOVL6-mediated elongation of monounsaturated fatty acids hampers remyelination by promoting inflammatory foam cell formation during demyelination. In cancer, alternative desaturation and elongation pathways increase cancer cell plasticity and affect ferroptosis sensitivity. In chronic liver disease, alterations in fatty acid elongation contribute to lipid remodeling and disease progression. In agriculture, the pathway is linked to intramuscular fat content in beef cattle. Thus, understanding this process has broad implications for neuroscience, oncology, hepatology, and animal science.
• Regulates membrane lipid composition and fluidity through production of longer monounsaturated fatty acids.
• Modulates inflammatory foam cell formation and remyelination in demyelinating diseases.
• Supports cancer cell plasticity by providing monounsaturated fatty acids for membrane synthesis.
• Contributes to lipid alterations in chronic liver disease and liver cancer.
• Influences ferroptosis sensitivity by altering phospholipid composition.
• Affects intramuscular fat content and meat quality traits in beef cattle.
• Is modulated by gut microbiota, linking host metabolism to microbial signals.
• Provides targets for CRISPR-based functional studies of ELOVL6 and related genes.
• Plays a role in triglyceride cycling and stored fatty acid modification.
• Has structural and functional parallels in plant ELO-like elongases.
What Happens During fatty acid elongation, monounsaturated fatty acid?
Substrate generation and desaturation
In simple terms: First, the cell makes a fatty acid with one double bond.
The process begins with the availability of a monounsaturated fatty acyl-CoA substrate, such as C16:1. This substrate can be generated by desaturases acting on saturated fatty acids, and alternative desaturation pathways can increase cancer cell plasticity by producing monounsaturated fatty acids. In the liver, gut microbiota promotes fatty acid desaturation and elongation, indicating that microbial signals can influence substrate supply. Triglyceride cycling also enables modification of stored fatty acids, potentially providing substrates for elongation.
Condensation and reduction steps
In simple terms: The elongase enzyme adds two carbons to the fatty acid chain.
ELOVL6 catalyzes the elongation of C16:1 to C18:1 through a series of reactions that add two carbon units to the carboxyl end of the monounsaturated fatty acid. This elongation activity is part of the fatty acid elongation cycle, which involves condensation, reduction, dehydration, and another reduction. The enzyme's preference for monounsaturated substrates distinguishes this process from saturated fatty acid elongation. Structural and functional analysis of plant ELO-like elongases has provided insights into the catalytic mechanism of these enzymes.
Product incorporation into lipids
In simple terms: The longer monounsaturated fatty acid is then used to build membrane and storage lipids.
The elongated monounsaturated fatty acids, such as C18:1, are incorporated into phospholipids, triglycerides, and other complex lipids. In demyelinating conditions, ELOVL6-mediated elongation promotes the formation of inflammatory foam cells, which impairs remyelination. In cancer cells, altered lipogenic enzyme expression and phospholipid composition affect ferroptosis sensitivity, highlighting the impact of elongation products on cell death pathways. Triglyceride cycling enables modification of stored fatty acids, further linking elongation to lipid storage dynamics.
Regulation by transcriptional programs
In simple terms: The cell controls this process by turning elongase genes on or off.
Transcription factors such as Zeb1 regulate lipogenic enzyme expression, including genes involved in fatty acid elongation, thereby influencing phospholipid composition and ferroptosis sensitivity in cancer cells. In chronic liver disease, lipid alterations include changes in fatty acid elongation, suggesting that disease-specific transcriptional programs modulate this pathway. In beef cattle, transcriptome and metabolome analyses reveal regulatory mechanisms of intramuscular fat content that involve fatty acid elongation. These examples show that GO:0034625 is subject to both cell-intrinsic and systemic regulation.
Key Genes Involved in GO:0034625 fatty acid elongation, monounsaturated fatty acid
The following genes and proteins are experimentally implicated in monounsaturated fatty acid elongation, based on the verified literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| ELOVL6 | Elongase that converts C16:1 to C18:1 | Key enzyme in monounsaturated fatty acid elongation; knockout impairs remyelination |
| SCD | Desaturase that introduces double bonds | Provides monounsaturated substrates for elongation; alternative desaturation pathways in cancer |
| ZEB1 | Transcription factor regulating lipogenic enzymes | Modulates fatty acid elongation and ferroptosis sensitivity |
| ELOVL1 | Elongase for saturated and monounsaturated fatty acids | May contribute to monounsaturated fatty acid elongation in specific tissues |
| ELOVL3 | Elongase involved in lipid metabolism | Potential role in monounsaturated fatty acid elongation |
| ELOVL5 | Elongase for polyunsaturated fatty acids | Can also elongate monounsaturated fatty acids in some contexts |
| ELOVL7 | Elongase with broad substrate specificity | May participate in monounsaturated fatty acid elongation |
| ACSL | Acyl-CoA synthetase | Activates fatty acids for elongation |
| DGAT | Diacylglycerol acyltransferase | Incorporates elongated fatty acids into triglycerides |
| ATGL | Adipose triglyceride lipase | Mobilizes stored fatty acids for elongation |
| HSL | Hormone-sensitive lipase | Contributes to triglyceride cycling and fatty acid release |
| PPARα | Nuclear receptor regulating lipid metabolism | May influence expression of elongation enzymes |
| SREBP1 | Transcription factor for lipogenic genes | Regulates elongase expression |
| FASN | Fatty acid synthase | Provides saturated fatty acid precursors for desaturation and elongation |
| SCD1 | Stearoyl-CoA desaturase 1 | Generates monounsaturated fatty acids for elongation |
| ELOVL2 | Elongase for polyunsaturated fatty acids | May have overlapping functions with ELOVL6 |
| ELOVL4 | Elongase for very long-chain fatty acids | Potential role in monounsaturated fatty acid elongation |
| GPAT | Glycerol-3-phosphate acyltransferase | Links elongated fatty acids to phospholipid synthesis |
How Is fatty acid elongation, monounsaturated fatty acid Regulated?
The process of monounsaturated fatty acid elongation is regulated at multiple levels. Substrate availability, determined by desaturase activity and triglyceride cycling, directly affects flux through the pathway. Transcriptional regulation by factors such as Zeb1 modulates the expression of lipogenic enzymes, including elongases, thereby influencing phospholipid composition and ferroptosis sensitivity. In the liver, gut microbiota promotes fatty acid desaturation and elongation, indicating that microbial metabolites can regulate this process. In chronic liver disease, alterations in lipid metabolism include changes in fatty acid elongation, suggesting that disease-associated signaling pathways impact this pathway. Additionally, in beef cattle, transcriptome and metabolome analyses reveal regulatory mechanisms of intramuscular fat content that involve fatty acid elongation.
fatty acid elongation, monounsaturated fatty acid and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| ELOVL6 | Demyelination and remyelination failure | Knockout mouse or oligodendrocyte-specific KO |
| ZEB1 | Cancer ferroptosis sensitivity | Cancer cell lines with Zeb1 knockout or overexpression |
| SCD | Cancer plasticity | Tumor models with SCD inhibition |
| ELOVL6 | Chronic liver disease | Liver-specific knockout or overexpression in mice |
| ELOVL6 | Intramuscular fat content | Beef cattle primary cells or CRISPR-edited models |
Demyelinating diseases
ELOVL6-mediated fatty acid elongation hampers remyelination by promoting inflammatory foam cell formation during demyelination. This suggests that inhibiting monounsaturated fatty acid elongation could be a therapeutic strategy to enhance remyelination in diseases such as multiple sclerosis.
Cancer
Alternative fatty acid desaturation pathways increase cancer plasticity, and Zeb1 regulates lipogenic enzyme expression and phospholipid composition to affect ferroptosis sensitivity. Monounsaturated fatty acid elongation contributes to the lipid repertoire that supports cancer cell survival and adaptation.
Chronic liver disease and liver cancer
Lipid alterations in chronic liver disease and liver cancer include changes in fatty acid elongation, which may contribute to disease progression and serve as biomarkers or therapeutic targets.
Metabolic and agricultural traits
In beef cattle, transcriptome and metabolome analyses reveal that fatty acid elongation is involved in regulating intramuscular fat content, a trait of economic importance. This highlights the broader relevance of this pathway beyond human disease.
From fatty acid elongation, monounsaturated fatty acid-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does ELOVL6 loss impair monounsaturated fatty acid elongation? | ELOVL6 knockout cell line or mouse |
| Does a point mutation in ELOVL6 alter substrate specificity? | CRISPR point mutation knock-in |
| Can tagged ELOVL6 reveal its subcellular localization? | Knock-in of fluorescent or epitope tag |
| Does ELOVL6 overexpression increase C18:1 levels? | Stable overexpression cell line |
| Which genes regulate monounsaturated fatty acid elongation? | CRISPR library screening |
| How does Zeb1 regulate lipogenic enzymes? | Zeb1 knockout or overexpression with lipidomics |
How to Study the fatty acid elongation, monounsaturated fatty acid Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Lipidomics (LC-MS) | Fatty acid species and elongation products | Quantify C16:1 to C18:1 conversion |
| RNA-seq | Gene expression changes | Identify regulators of elongation |
| Metabolomics | Metabolite levels | Link elongation to metabolic pathways |
| CRISPR knockout screening | Gene essentiality for elongation | Discover novel regulators |
| Enzyme activity assay | Elongase catalytic activity | Measure ELOVL6 function |
| Western blot | Protein expression | Validate knockout or overexpression |
| Immunofluorescence | Subcellular localization | Determine ER localization of elongases |
| Triglyceride cycling assay | Fatty acid storage and release | Study stored fatty acid modification |
Lipidomics and mass spectrometry
Lipidomics using mass spectrometry is essential to quantify monounsaturated fatty acid species and their elongation products. This approach has been used to show that ELOVL6 elongation produces C18:1 and affects membrane composition.
Transcriptomics and metabolomics
RNA-seq and metabolomics reveal regulatory mechanisms of fatty acid elongation. In beef cattle, integrated transcriptome and metabolome analysis identified pathways linked to intramuscular fat content. Similar approaches can be applied to human cells to identify regulators of GO:0034625.
CRISPR screening and functional genomics
CRISPR knockout screens can identify genes required for monounsaturated fatty acid elongation. Such screens have been used to uncover regulators of ferroptosis sensitivity and lipogenic enzyme expression.
Enzyme activity assays
In vitro elongase assays using radiolabeled or fluorescent substrates measure the catalytic activity of ELOVL enzymes. Structural and functional analysis of plant ELO-like elongases provides a framework for understanding eukaryotic elongase mechanisms.
How CRISPR Can Be Used to Study GO:0034625 fatty acid elongation, monounsaturated fatty acid
Knockout
CRISPR knockout of ELOVL6 or other elongases can abolish monounsaturated fatty acid elongation, leading to altered lipid composition and cellular phenotypes. For example, ELOVL6 knockout impairs remyelination by reducing inflammatory foam cell formation.
Point Mutation
Point mutations can be introduced into the catalytic domain of ELOVL6 to dissect substrate specificity and catalytic mechanism. Such models help determine which residues are essential for elongating monounsaturated fatty acids.
Knock-in
Knock-in of tags or reporters into the endogenous ELOVL6 locus allows real-time tracking of enzyme expression and localization. This approach can reveal dynamic regulation of monounsaturated fatty acid elongation in living cells.
Overexpression
Overexpression of ELOVL6 or other elongases increases flux through the monounsaturated fatty acid elongation pathway, enabling studies of lipid accumulation and downstream signaling. This has been used to show that ELOVL6 promotes foam cell formation.
How EDITGENE Supports fatty acid elongation, monounsaturated fatty acid Research
Researchers studying fatty acid elongation, monounsaturated fatty acid-related genes often need to determine whether a candidate gene is causally involved in the pathway or merely correlated with lipid changes. EDITGENE provides CRISPR-based services to establish causality through precise genome editing.
Contact EDITGENE today to design your custom CRISPR model for fatty acid elongation, monounsaturated fatty acid research.
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ELOVL5 Knockout HEK293 Cell Line | EDJ-KQ3092 | Human | 60481 | Details Get a Quote |
| ELOVL4 Knockout HEK293 Cell Line | EDJ-KQ3151 | Human | 6785 | Details Get a Quote |
| ELOVL3 Knockout HEK293 Cell Line | EDJ-KQ9839 | Human | 83401 | Details Get a Quote |
| ELOVL2 Knockout HEK293 Cell Line | EDJ-KQ11923 | Human | 54898 | Details Get a Quote |
| ELOVL1 Knockout HEK293 Cell Line | EDJ-KQ13277 | Human | 64834 | Details Get a Quote |
| ELOVL6 Knockout HEK293 Cell Line | EDJ-KQ13278 | Human | 79071 | Details Get a Quote |
| ELOVL7 Knockout HEK293 Cell Line | EDJ-KQ13280 | Human | 79993 | Details Get a Quote |
| ELOVL4 Knockout HeLa Cell Line | EDJ-KQ23165 | Human | 6785 | Details Get a Quote |
| ELOVL7 Knockout A-549 Cell Line | EDJ-KQ41475 | Human | 79993 | Details Get a Quote |
| ELOVL5 Knockout A-549 Cell Line | EDJ-KQ24403 | Human | 60481 | Details Get a Quote |
| ELOVL5 Knockout HCT 116 Cell Line | EDJ-KQ24404 | Human | 60481 | Details Get a Quote |
| ELOVL5 Knockout HeLa Cell Line | EDJ-KQ24405 | Human | 60481 | Details Get a Quote |
| ELOVL4 Knockout A-549 Cell Line | EDJ-KQ24550 | Human | 6785 | Details Get a Quote |
| ELOVL3 Knockout A-549 Cell Line | EDJ-KQ36686 | Human | 83401 | Details Get a Quote |
| ELOVL3 Knockout HCT 116 Cell Line | EDJ-KQ36687 | Human | 83401 | Details Get a Quote |
Displaying Records 1 To 15 Of 28 Records
Frequently Asked Questions About fatty acid elongation, monounsaturated fatty acid
What is GO:0034625?
GO:0034625 is the Gene Ontology term for fatty acid elongation, monounsaturated fatty acid, the process of elongating a fatty acid chain that already contains one C-C double bond.
What genes are involved in fatty acid elongation, monounsaturated fatty acid?
Key genes include ELOVL6, SCD, ZEB1, and other ELOVL family members, as well as genes involved in triglyceride cycling.
Which enzyme catalyzes monounsaturated fatty acid elongation?
ELOVL6 is a principal enzyme that catalyzes the elongation of C16:1 to C18:1, a monounsaturated fatty acid.
How is monounsaturated fatty acid elongation regulated?
It is regulated by substrate availability, desaturase activity, transcriptional programs such as Zeb1, and gut microbiota signals.
What diseases are associated with monounsaturated fatty acid elongation?
It is associated with demyelinating diseases, cancer, chronic liver disease, and metabolic traits in livestock.
How can I study monounsaturated fatty acid elongation using CRISPR?
CRISPR knockout, point mutation, knock-in, and overexpression models allow causal interrogation of genes like ELOVL6 in this pathway.
What methods measure monounsaturated fatty acid elongation?
Lipidomics, enzyme activity assays, RNA-seq, and metabolomics are commonly used to measure this process.
Does ELOVL6 affect remyelination?
Yes, ELOVL6-mediated elongation hampers remyelination by promoting inflammatory foam cell formation during demyelination.
Is monounsaturated fatty acid elongation important in cancer?
Yes, it contributes to cancer cell plasticity and ferroptosis sensitivity through altered lipid composition.
Can gut microbiota influence monounsaturated fatty acid elongation?
Yes, gut microbiota promotes hepatic fatty acid desaturation and elongation in mice.
Conclusion
GO:0034625, fatty acid elongation, monounsaturated fatty acid, is a fundamental lipid metabolic process with far-reaching implications for cell membrane biology, inflammation, cancer, and metabolic disease. The enzyme ELOVL6 and its regulators are central to this pathway, and their dysfunction contributes to remyelination failure, cancer progression, and liver disease. CRISPR-based models provide powerful tools to dissect the causal roles of specific genes in this process. Continued research into this pathway will likely yield new therapeutic strategies and biomarkers for a range of human diseases.
References
- 1. Garcia Corrales AV et al.. 2023. Fatty acid elongation by ELOVL6 hampers remyelination by promoting inflammatory foam cell formation during demyelination.. Proc Natl Acad Sci U S A 120(37):e2301030120 PMID: 37669365
- 2. Paul B et al.. 2022. Lipid alterations in chronic liver disease and liver cancer.. JHEP Rep 4(6):100479 PMID: 35469167
- 3. Schwab A et al.. 2024. Zeb1 mediates EMT/plasticity-associated ferroptosis sensitivity in cancer cells by regulating lipogenic enzyme expression and phospholipid composition.. Nat Cell Biol 26(9):1470-1481 PMID: 39009641
- 4. Vriens K et al.. 2019. Evidence for an alternative fatty acid desaturation pathway increasing cancer plasticity.. Nature 566(7744):403-406 PMID: 30728499
- 5. Yu H et al.. 2024. Comprehensive Analysis of Transcriptome and Metabolome Reveals Regulatory Mechanism of Intramuscular Fat Content in Beef Cattle.. J Agric Food Chem 72(6):2911-2924 PMID: 38303491
- 6. Wunderling K et al.. 2023. Triglyceride cycling enables modification of stored fatty acids.. Nat Metab 5(4):699-709 PMID: 37012495
- 7. Meesapyodsuk D et al.. 2024. Structural and functional analysis of plant ELO-like elongase for fatty acid elongation.. Plant Mol Biol 114(5):90 PMID: 39172265
- 8. Kindt A et al.. 2018. The gut microbiota promotes hepatic fatty acid desaturation and elongation in mice.. Nat Commun 9(1):3760 PMID: 30218046
