GO:0008152 metabolic process: Biochemical Pathways, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0008152 metabolic process describes the biochemical pathways by which a living organism transforms chemical substances, encompassing both anabolism (biosynthetic processes) and catabolism (catabolic processes).
• Metabolic processes include the transformation of small molecules as well as macromolecular processes such as DNA repair and replication, protein synthesis and degradation.
• Metabolic reprogramming is a hallmark of the tumor microenvironment in liver cancer, where altered metabolic pathways support cancer cell proliferation and survival.
• Species-specific metabolic reprogramming occurs in human and mouse microglia during inflammatory pathway induction, highlighting the importance of model system choice.
• Plasma membrane electron transport is a metabolic process deserving of renewed interest, linking redox biology to cellular metabolism.
• Urea metabolism represents a critical metabolic process for nitrogen disposal, with implications for liver and kidney function.
Description
Metabolic process (GO:0008152) is a fundamental biological process that encompasses the biochemical pathways by which a living organism transforms chemical substances. This includes anabolism, the biosynthetic process, and catabolism, the catabolic process, covering both small molecule transformations and macromolecular processes such as DNA repair and replication, protein synthesis and degradation. Understanding metabolic process is essential for researchers because dysregulation of these pathways underlies numerous human diseases, including cancer, metabolic disorders, and neurodegenerative conditions [1, 2]. For example, metabolic reprogramming in the tumor microenvironment of liver cancer supports cancer cell proliferation and survival, making metabolic pathways attractive therapeutic targets. Similarly, species-specific metabolic reprogramming in human and mouse microglia during inflammatory pathway induction underscores the importance of model system selection in metabolic research. Plasma membrane electron transport, a metabolic process deserving of renewed interest, further illustrates the broad scope of metabolic activities that impact cellular function. Urea metabolism, a critical metabolic process for nitrogen disposal, is essential for liver and kidney function. Given the breadth and complexity of metabolic processes, researchers require robust experimental models and methods to dissect the roles of specific genes and pathways. This article provides a comprehensive overview of GO:0008152 metabolic process, including its definition, key genes, regulatory mechanisms, disease associations, and research methodologies, with a focus on CRISPR-based approaches for functional genomics.
metabolic process At A Glance
| GO ID | GO:0008152 |
|---|---|
| GO term | metabolic process |
| Ontology | biological_process |
| Synonym | metabolism |
| Major function | Transformation of chemical substances through anabolic and catabolic pathways |
| Scope | Includes small molecule transformations and macromolecular processes such as DNA repair, replication, protein synthesis, and degradation |
| Related diseases | Cancer, metabolic disorders, neurodegenerative diseases, inflammatory conditions |
| Research methods | CRISPR knockout, point mutation, knock-in, overexpression, metabolic profiling, CRISPR library screening |
What Is GO:0008152?
According to the Gene Ontology, GO:0008152 metabolic process is defined as a cellular process consisting of the biochemical pathways by which a living organism transforms chemical substances. This includes anabolism (biosynthetic process) and catabolism (catabolic process). Metabolic processes include the transformation of small molecules, as well as macromolecular processes such as DNA repair and replication, protein synthesis and degradation. The synonym for this term is metabolism.
Why Is metabolic process Important in Cell Biology?
Metabolic process (GO:0008152) is critically important because it governs the biochemical transformations that sustain life, and its dysregulation is a central feature of many human diseases, including cancer, metabolic disorders, and inflammatory conditions [1, 2]. For instance, metabolic reprogramming in the tumor microenvironment of liver cancer supports cancer cell proliferation and survival, making metabolic pathways key therapeutic targets. Species-specific metabolic reprogramming in human and mouse microglia during inflammatory pathway induction further highlights the need to understand metabolic processes in a context-dependent manner. Plasma membrane electron transport, a metabolic process deserving of renewed interest, links redox biology to cellular metabolism and has implications for cancer and aging. Urea metabolism is essential for nitrogen disposal, and its dysfunction leads to hyperammonemia and related disorders. Thus, studying metabolic processes is fundamental to understanding disease mechanisms and developing effective interventions.
• Metabolic process (GO:0008152) encompasses all biochemical pathways that transform chemical substances, including anabolism and catabolism.
• Dysregulation of metabolic processes is a hallmark of cancer, as seen in metabolic reprogramming in the tumor microenvironment of liver cancer.
• Species-specific metabolic reprogramming in human and mouse microglia during inflammatory pathway induction affects neuroinflammation and neurodegeneration.
• Plasma membrane electron transport is a metabolic process that modulates cellular redox state and has been linked to cancer and aging.
• Urea metabolism is critical for nitrogen disposal, and its impairment causes hyperammonemia and liver/kidney disorders.
• S-acylation regulates SQSTM1/p62-mediated selective autophagy, linking metabolic processes to protein degradation and cellular quality control.
• GLUT4 exocytosis is a metabolic process that regulates glucose uptake, with implications for diabetes and insulin resistance.
• Biodegradation of neonicotinoid insecticides by microorganisms involves metabolic processes and metabolic enzymes, relevant for environmental toxicology.
• Metabolic regulation of dendritic cell differentiation affects immune responses and tolerance.
• Understanding metabolic processes enables the development of targeted therapies for metabolic diseases, cancer, and inflammatory disorders [1, 2, 8].
What Happens During metabolic process?
Anabolism (Biosynthetic Processes)
In simple terms: Anabolism is the building-up part of metabolism, where cells use energy to make complex molecules from simpler ones.
Anabolism encompasses the biosynthetic pathways that construct complex molecules from simpler precursors, consuming energy in the form of ATP and reducing equivalents. This includes the synthesis of macromolecules such as proteins, nucleic acids, carbohydrates, and lipids. For example, protein synthesis is a macromolecular metabolic process that translates genetic information into functional polypeptides. Anabolic pathways are tightly regulated to meet cellular demands for growth and proliferation, and their dysregulation contributes to diseases such as cancer, where biosynthetic processes are upregulated to support rapid cell division.
Catabolism (Catabolic Processes)
In simple terms: Catabolism is the breaking-down part of metabolism, where cells degrade complex molecules to release energy and simple building blocks.
Catabolism involves the degradation of complex molecules into simpler ones, releasing energy that is captured as ATP or reducing equivalents. This includes processes such as glycolysis, fatty acid oxidation, and protein degradation. For instance, selective autophagy mediated by SQSTM1/p62 is a catabolic process that degrades damaged proteins and organelles, and its regulation by S-acylation highlights the interplay between post-translational modifications and metabolic degradation. Catabolic pathways are essential for recycling cellular components and maintaining energy homeostasis, and their dysfunction is linked to neurodegenerative diseases and metabolic disorders.
Small Molecule Transformations
In simple terms: Small molecule transformations are the chemical reactions that convert simple compounds like sugars, amino acids, and lipids into other molecules the cell needs.
Metabolic processes include the transformation of small molecules, such as glucose, amino acids, nucleotides, and lipids. These transformations are catalyzed by enzymes and are organized into interconnected pathways. For example, urea metabolism converts ammonia to urea for excretion, a critical process for nitrogen disposal. GLUT4 exocytosis regulates glucose uptake, a key step in glucose metabolism. The biodegradation of neonicotinoid insecticides by microorganisms involves metabolic enzymes that transform these xenobiotics into metabolites, which is relevant for environmental toxicology. Small molecule transformations are essential for energy production, biosynthesis, and detoxification.
Macromolecular Processes
In simple terms: Macromolecular processes are the metabolic activities that manage large molecules like DNA, RNA, and proteins, including their synthesis and breakdown.
Metabolic processes also encompass macromolecular processes such as DNA repair and replication, protein synthesis, and degradation. These processes are vital for maintaining genomic integrity and proteostasis. For example, DNA repair is a metabolic process that corrects damage to DNA, and its impairment leads to mutations and cancer. Protein synthesis and degradation are balanced to maintain cellular function, and their dysregulation is implicated in cancer and neurodegeneration [1, 5]. The metabolic regulation of dendritic cell differentiation further illustrates how macromolecular processes influence immune cell fate.
Metabolic Reprogramming in Disease
In simple terms: Metabolic reprogramming is when cells change their metabolic pathways to support disease, such as cancer growth or inflammation.
Metabolic reprogramming is a hallmark of many diseases, where cells alter their metabolic pathways to support pathological states. In the tumor microenvironment of liver cancer, metabolic reprogramming supports cancer cell proliferation and survival. Species-specific metabolic reprogramming in human and mouse microglia during inflammatory pathway induction highlights the importance of context in metabolic studies. Plasma membrane electron transport is a metabolic process that modulates cellular redox and has been linked to cancer and aging. Understanding these reprogramming events can reveal therapeutic vulnerabilities.
Key Genes Involved in GO:0008152 metabolic process
The following table lists key genes and proteins involved in metabolic process (GO:0008152), along with their major roles and research relevance.
| Gene | Major Role | Research Relevance |
|---|---|---|
| SQSTM1 | Selective autophagy receptor regulated by S-acylation | Links metabolic degradation to protein quality control |
| GLUT4 | Insulin-responsive glucose transporter | Regulates glucose uptake and metabolism |
| mTOR | Central regulator of cell growth and metabolism | Coordinates anabolic and catabolic pathways |
| HIF1A | Hypoxia-inducible factor 1-alpha | Drives metabolic reprogramming in cancer |
| MYC | Oncogenic transcription factor | Promotes biosynthetic metabolism in cancer |
| TP53 | Tumor suppressor | Regulates metabolic pathways in response to stress |
| AMPK | Energy sensor kinase | Activates catabolic pathways during energy stress |
| PGC1A | Transcriptional coactivator | Regulates mitochondrial biogenesis and metabolism |
| CPT1A | Carnitine palmitoyltransferase 1A | Rate-limiting enzyme for fatty acid oxidation |
| LDHA | Lactate dehydrogenase A | Catalyzes conversion of pyruvate to lactate in glycolysis |
| PKM | Pyruvate kinase M | Regulates glycolytic flux and biosynthetic metabolism |
| G6PD | Glucose-6-phosphate dehydrogenase | Rate-limiting enzyme of pentose phosphate pathway |
| ACACA | Acetyl-CoA carboxylase alpha | Regulates fatty acid synthesis |
| FASN | Fatty acid synthase | Catalyzes fatty acid synthesis |
| CPS1 | Carbamoyl phosphate synthetase 1 | Rate-limiting enzyme of urea cycle |
| OTC | Ornithine transcarbamylase | Urea cycle enzyme |
| ASS1 | Argininosuccinate synthase 1 | Urea cycle enzyme |
How Is metabolic process Regulated?
Metabolic process (GO:0008152) is regulated at multiple levels, including transcriptional, post-translational, and allosteric mechanisms. Central regulators such as mTOR coordinate anabolic and catabolic pathways in response to nutrient availability and growth signals. AMPK acts as an energy sensor that activates catabolic pathways when cellular energy is low. Hypoxia-inducible factor 1-alpha (HIF1A) drives metabolic reprogramming under hypoxic conditions, promoting glycolysis and angiogenesis in cancer. Post-translational modifications, such as S-acylation, regulate selective autophagy mediated by SQSTM1/p62, linking metabolic degradation to cellular stress responses. Species-specific differences in metabolic regulation, as observed in human and mouse microglia during inflammatory pathway induction, highlight the importance of context in studying metabolic processes. Additionally, metabolic regulation of dendritic cell differentiation demonstrates how metabolic pathways influence immune cell fate.
metabolic process and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| HIF1A | Liver cancer metabolic reprogramming | Knockout in liver cancer cell lines |
| SQSTM1 | Neurodegeneration and autophagy dysfunction | Point mutation knock-in in neuronal cells |
| CPS1 | Urea cycle disorder and hyperammonemia | Knockout in hepatocytes |
| GLUT4 | Type 2 diabetes and insulin resistance | Overexpression in adipocytes |
| mTOR | Cancer and metabolic disorders | Knockout in cancer cell lines |
Metabolic Reprogramming in Cancer
Metabolic reprogramming is a hallmark of cancer, enabling tumor cells to meet the biosynthetic and energetic demands of rapid proliferation. In liver cancer, the tumor microenvironment undergoes metabolic reprogramming that supports cancer cell survival and immune evasion. Key pathways such as glycolysis, glutaminolysis, and fatty acid synthesis are upregulated, often driven by oncogenes like MYC and HIF1A. Targeting these metabolic alterations is a promising therapeutic strategy, and CRISPR-based models can help identify metabolic vulnerabilities.
Metabolic Dysregulation in Neuroinflammation and Neurodegeneration
Metabolic processes in microglia are critical for brain homeostasis, and their dysregulation contributes to neuroinflammation and neurodegeneration. Species-specific metabolic reprogramming in human and mouse microglia during inflammatory pathway induction has been observed, which may affect the translation of findings from mouse models to human diseases. Understanding these metabolic differences is essential for developing effective therapies for neurodegenerative conditions.
Urea Cycle Disorders and Hyperammonemia
Urea metabolism is a critical metabolic process for nitrogen disposal, and its impairment leads to hyperammonemia and related disorders. Deficiencies in urea cycle enzymes such as CPS1, OTC, and ASS1 cause inherited metabolic diseases that can be life-threatening. Research into urea cycle regulation and its metabolic integration is important for developing treatments for these disorders.
Metabolic Regulation of Immune Responses
Metabolic processes regulate immune cell differentiation and function. For example, metabolic regulation of dendritic cell differentiation affects immune responses and tolerance. Dysregulation of these metabolic pathways can contribute to autoimmune diseases and cancer immune evasion. Studying metabolic processes in immune cells can reveal new targets for immunotherapy.
From metabolic process-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X regulate metabolic flux in cancer cells? | CRISPR knockout in cancer cell lines followed by metabolic profiling |
| Does a specific point mutation in gene Y alter enzyme activity? | CRISPR point mutation knock-in in isogenic cell lines |
| Does overexpression of gene Z promote metabolic reprogramming? | CRISPR overexpression in primary cells |
| How does a tagged metabolic enzyme localize in live cells? | CRISPR knock-in of fluorescent tag |
| Which metabolic genes are essential for immune cell differentiation? | CRISPR library screening in primary immune cells |
| Does a species-specific metabolic difference affect drug response? | CRISPR knockout in human and mouse microglia |
How to Study the metabolic process Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Metabolic profiling (LC-MS) | Metabolite abundance and isotopic labeling | Assessing metabolic reprogramming in cancer |
| CRISPR library screening | Gene essentiality for metabolic phenotypes | Identifying metabolic vulnerabilities [1, 8] |
| Proteomics | Protein abundance and modifications | Studying regulation of metabolic enzymes |
| Live-cell imaging | Metabolite dynamics and localization | Visualizing glucose uptake and metabolism |
| RNA-seq | Transcriptional changes in metabolic genes | Analyzing metabolic gene expression |
| Seahorse assay | Oxygen consumption and extracellular acidification | Measuring oxidative phosphorylation and glycolysis |
| Western blot | Protein expression and phosphorylation | Validating metabolic pathway activation |
| Immunofluorescence | Protein localization and interactions | Studying metabolic enzyme localization |
Metabolic Profiling and Flux Analysis
Metabolic profiling using mass spectrometry or nuclear magnetic resonance (NMR) allows researchers to measure metabolite levels and isotopic labeling to assess metabolic flux. These methods are essential for understanding how genetic perturbations affect metabolic pathways. For example, metabolic profiling of liver cancer cells can reveal reprogramming events in the tumor microenvironment.
CRISPR Screening for Metabolic Genes
CRISPR library screening enables unbiased identification of genes required for metabolic processes. Pooled knockout screens can be combined with metabolic selection or sorting to discover metabolic vulnerabilities in cancer or immune cells [1, 8]. This approach is powerful for identifying novel regulators of metabolic pathways.
Proteomics and Post-Translational Modification Analysis
Proteomics can quantify protein abundance and post-translational modifications that regulate metabolic enzymes. For instance, S-acylation of SQSTM1/p62 regulates selective autophagy, and proteomic methods can identify such modifications. These techniques are crucial for understanding metabolic regulation at the protein level.
Imaging and Live-Cell Metabolic Sensors
Genetically encoded fluorescent sensors can monitor metabolites such as ATP, NADH, and glucose in live cells. These imaging approaches provide spatial and temporal resolution of metabolic processes. For example, GLUT4 exocytosis can be visualized using tagged transporters.
How CRISPR Can Be Used to Study GO:0008152 metabolic process
Knockout
CRISPR knockout is used to completely ablate a gene of interest to study its role in metabolic processes. For example, knocking out HIF1A in liver cancer cells can reveal its contribution to metabolic reprogramming. Knockout models are essential for determining whether a gene is required for a specific metabolic pathway.
Point Mutation
CRISPR point mutation knock-in allows the introduction of specific amino acid changes to study enzyme activity or post-translational modification sites. For instance, mutating the S-acylation site of SQSTM1/p62 can reveal its role in selective autophagy. This approach is valuable for dissecting molecular mechanisms of metabolic enzymes.
Knock-in
CRISPR knock-in can insert tags, reporters, or humanized sequences into endogenous loci. Tagging metabolic enzymes with fluorescent proteins enables live-cell imaging of their localization and dynamics. Knock-in of disease-associated mutations can model metabolic disorders.
Overexpression
CRISPR overexpression (e.g., via CRISPRa) can increase the expression of metabolic genes to study gain-of-function effects. Overexpressing GLUT4 in adipocytes can enhance glucose uptake and provide insights into insulin resistance. This approach complements knockout studies.
How EDITGENE Supports metabolic process Research
Researchers studying metabolic process-related genes often need to determine whether a candidate gene is causally involved in a specific metabolic pathway or disease phenotype. EDITGENE provides a comprehensive suite of CRISPR-based services to enable precise genetic modifications in cell models, facilitating functional studies of metabolic genes.
Contact EDITGENE today to design your custom CRISPR model for metabolic process research.
Frequently Asked Questions About metabolic process
What is GO:0008152 metabolic process?
GO:0008152 metabolic process is a Gene Ontology term defined as the biochemical pathways by which a living organism transforms chemical substances, including anabolism and catabolism, covering small molecules and macromolecular processes such as DNA repair, replication, protein synthesis, and degradation.
What genes are involved in metabolic process?
Key genes involved in metabolic process include SQSTM1, GLUT4, mTOR, HIF1A, MYC, TP53, AMPK, PGC1A, CPT1A, LDHA, PKM, G6PD, ACACA, FASN, CPS1, OTC, and ASS1, among many others [1, 4, 5, 6].
How is metabolic process regulated?
Metabolic process is regulated by central kinases such as mTOR and AMPK, transcription factors like HIF1A and MYC, and post-translational modifications such as S-acylation, which control anabolic and catabolic pathways in response to nutrient and energy status [1, 5].
What diseases are associated with metabolic process dysfunction?
Dysregulation of metabolic processes is associated with cancer, neuroinflammation, neurodegeneration, urea cycle disorders, hyperammonemia, diabetes, and immune disorders [1, 2, 4, 8].
How can CRISPR be used to study metabolic process?
CRISPR can be used to create knockout, point mutation, knock-in, and overexpression cell models to dissect the roles of specific genes in metabolic pathways, and CRISPR library screening can identify novel metabolic regulators [1, 5, 6, 8].
What is metabolic reprogramming in cancer?
Metabolic reprogramming in cancer refers to the alteration of metabolic pathways in tumor cells and the tumor microenvironment to support proliferation and survival, often driven by oncogenes like HIF1A and MYC.
What is the role of urea metabolism?
Urea metabolism is a critical metabolic process for nitrogen disposal, converting toxic ammonia to urea for excretion, and its impairment leads to hyperammonemia and urea cycle disorders.
How does S-acylation regulate metabolism?
S-acylation regulates SQSTM1/p62-mediated selective autophagy, a catabolic process that degrades damaged proteins and organelles, linking post-translational modifications to metabolic degradation.
What is GLUT4 exocytosis?
GLUT4 exocytosis is a metabolic process that translocates glucose transporter type 4 to the cell membrane in response to insulin, facilitating glucose uptake and regulating glucose metabolism.
What methods are used to study metabolic process?
Common methods include metabolic profiling, CRISPR screening, proteomics, live-cell imaging, RNA-seq, Seahorse assays, Western blot, and immunofluorescence [1, 2, 5, 6].
Conclusion
Metabolic process (GO:0008152) is a foundational biological process that encompasses all biochemical transformations in living organisms, from small molecule metabolism to macromolecular synthesis and degradation. Its dysregulation is central to many human diseases, including cancer, neuroinflammation, and metabolic disorders [1, 2, 4]. Advances in CRISPR-based gene editing and screening technologies have revolutionized the study of metabolic processes, enabling precise functional interrogation of metabolic genes in relevant cell models [1, 5, 6, 8]. EDITGENE provides comprehensive CRISPR services to support researchers in dissecting metabolic pathways and developing novel therapeutic strategies.
References
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- 2. Sabogal-Guáqueta AM et al.. 2023. Species-specific metabolic reprogramming in human and mouse microglia during inflammatory pathway induction.. Nat Commun 14(1):6454 PMID: 37833292
- 3. Morré DJ et al.. 2004. Plasma membrane electron transport. A metabolic process deserving of renewed interest.. Biofactors 20(4):183-7 PMID: 15706054
- 4. Wang H et al.. 2014. Urea.. Subcell Biochem 73:7-29 PMID: 25298336
- 5. Huang X et al.. 2024. S-acylation regulates SQSTM1/p62-mediated selective autophagy.. Autophagy 20(6):1467-1469 PMID: 38124295
- 6. Stöckli J et al.. 2011. GLUT4 exocytosis.. J Cell Sci 124(Pt 24):4147-59 PMID: 22247191
- 7. Zhao YX et al.. 2025. Biodegradation of Neonicotinoid Insecticides Thiacloprid and Thiamethoxam by Microorganisms: Metabolic Process, Metabolic Enzymes and Toxicity Assessments of their Metabolites.. Curr Microbiol 82(8):347 PMID: 40555881
- 8. He Z et al.. 2019. Metabolic Regulation of Dendritic Cell Differentiation.. Front Immunol 10:410 PMID: 30930893
