GO:0019752 carboxylic acid metabolic process: Pathway, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0019752 (carboxylic acid metabolic process) describes all chemical reactions and pathways involving carboxylic acids, organic acids with one or more carboxyl (COOH) groups or carboxylate anions (COO-).
• Carboxylic acid reductases (CARs) are key enzymes that convert carboxylic acids to aldehydes, a reaction exploited in metabolic engineering for producing fuels and chemicals [1,2].
• Carboxylic acid transporters are critical for uptake and efflux of these metabolites, and in Candida species they contribute to pathogenesis and drug resistance.
• Metabolic activation of carboxylic acids can generate reactive intermediates that cause toxicity, a major consideration in drug metabolism and safety.
• Hydroxy-carboxylic acid receptors (e.g., HCA1/GPR81, HCA2/GPR109A) mediate signaling effects of lactate, beta-hydroxybutyrate, and other carboxylic acids in metabolism.
• Emerging environmental contaminants such as hexafluoropropylene oxide trimer carboxylic acid (HFPO-TA) interact with biological systems, highlighting the need to study carboxylic acid metabolism in toxicology.
Description
Carboxylic acid metabolic process (GO:0019752) encompasses the chemical reactions and pathways involving carboxylic acids, which are organic acids containing one or more carboxyl (COOH) groups or their anions (COO-). This broad ontological term captures essential biochemical transformations that range from central carbon metabolism to the synthesis and degradation of fatty acids, amino acids, and secondary metabolites. Carboxylic acids are ubiquitous in living systems, serving as metabolic intermediates, signaling molecules, and building blocks for macromolecules. The importance of this process is underscored by the diversity of enzymes that act on carboxylic acids, including carboxylic acid reductases (CARs) that catalyze the ATP- and NADPH-dependent reduction of carboxylic acids to aldehydes [1,2]. These enzymes are of significant interest in metabolic engineering for the sustainable production of fuels and chemicals. Moreover, carboxylic acid transporters mediate the movement of these compounds across cellular membranes, a process critical for nutrient acquisition and pathogenesis in organisms such as Candida albicans. In humans, carboxylic acids participate in drug metabolism, where metabolic activation can lead to toxic intermediates, and they act as signaling molecules through receptors like HCA1 and HCA2. Understanding the regulation and mechanisms of carboxylic acid metabolic process is therefore fundamental to biochemistry, pharmacology, and biotechnology.
carboxylic acid metabolic process At A Glance
| GO ID | GO:0019752 |
|---|---|
| GO term | carboxylic acid metabolic process |
| Ontology | biological_process |
| Synonym | carboxylic acid metabolism |
| Definition | The chemical reactions and pathways involving carboxylic acids, any organic acid containing one or more carboxyl (COOH) groups or anions (COO-). |
| Major function | Metabolism of carboxylic acids, including their synthesis, degradation, and interconversion. |
| Related enzymes | Carboxylic acid reductases (CARs), oxidoreductases, transferases, hydrolases, lyases, isomerases, ligases. |
| Related transporters | Carboxylic acid transporters (e.g., in Candida species). |
| Signaling receptors | Hydroxy-carboxylic acid receptors (HCA1, HCA2, HCA3). |
| Key pathways | Fatty acid metabolism, amino acid metabolism, TCA cycle, drug metabolism. |
What Is GO:0019752?
According to the Gene Ontology, carboxylic acid metabolic process (GO:0019752) is defined as the chemical reactions and pathways involving carboxylic acids, any organic acid containing one or more carboxyl (COOH) groups or anions (COO-). This term is a broad biological process category that includes both the synthesis (anabolism) and breakdown (catabolism) of carboxylic acids, as well as their interconversion and conjugation. It covers metabolic steps such as decarboxylation, reduction, oxidation, and transport-mediated processes that involve carboxylic acid substrates or products. The synonym carboxylic acid metabolism is used interchangeably.
Why Is carboxylic acid metabolic process Important in Cell Biology?
Carboxylic acid metabolic process is fundamental to all living organisms because carboxylic acids are central intermediates in energy production, biosynthesis, and cellular signaling. In biotechnology, carboxylic acid reductases are harnessed to convert renewable carboxylic acids into aldehydes, which are valuable precursors for biofuels and pharmaceuticals [1,2]. In medicine, the metabolic activation of carboxylic acids can produce reactive metabolites that cause toxicity, making this process critical in drug development and safety assessment. Additionally, carboxylic acid transporters in pathogenic fungi like Candida albicans are essential for virulence and represent potential drug targets. Hydroxy-carboxylic acid receptors mediate the effects of metabolites such as lactate and beta-hydroxybutyrate on metabolism and inflammation. Environmental contaminants such as HFPO-TA are carboxylic acids that can disrupt biological systems, underscoring the need for toxicological studies. Thus, understanding carboxylic acid metabolic process has broad implications for health, disease, and industrial applications.
• Central to energy metabolism: carboxylic acids such as pyruvate, citrate, and fatty acids are key intermediates in the TCA cycle and beta-oxidation.
• Biotechnological production: carboxylic acid reductases enable the conversion of carboxylic acids to aldehydes for biofuel and chemical synthesis [1,2].
• Drug metabolism and toxicity: metabolic activation of carboxylic acids can form reactive acyl glucuronides or CoA thioesters, leading to adverse drug reactions.
• Pathogen virulence: carboxylic acid transporters in Candida albicans are required for nutrient acquisition and pathogenesis.
• Signaling roles: hydroxy-carboxylic acid receptors (HCA1-3) mediate metabolic and inflammatory responses to lactate, beta-hydroxybutyrate, and other acids.
• Environmental toxicology: per- and polyfluoroalkyl substances (PFAS) such as HFPO-TA are carboxylic acids that bioaccumulate and may disrupt metabolism.
• Metabolic engineering: CAR enzymes are used to produce aldehydes from fatty acids and other carboxylic acids in microbial cell factories.
• Cancer metabolism: altered carboxylic acid metabolism, including lactate and glutamine pathways, supports tumor growth and survival.
• Neurodegeneration: dysregulated carboxylic acid metabolism, such as in fatty acid oxidation disorders, can affect neuronal function.
• Drug discovery: enzymes and transporters in carboxylic acid metabolism are targets for antibiotics, antifungals, and anticancer agents.
What Happens During carboxylic acid metabolic process?
Carboxylic Acid Reduction by CAR Enzymes
In simple terms: Carboxylic acid reductases (CARs) are enzymes that turn carboxylic acids into aldehydes, a reaction that requires ATP and NADPH.
Carboxylic acid reductases (CARs) catalyze the ATP- and NADPH-dependent reduction of carboxylic acids to their corresponding aldehydes. This reaction proceeds through a two-step mechanism involving the formation of an adenylate intermediate and subsequent reduction by the reductase domain. Structural and mechanistic studies have elucidated the domain architecture of CARs, which typically consist of an adenylation domain, a thiolation domain, and a reductase domain. These enzymes are found in bacteria and fungi and play a role in natural product biosynthesis and catabolism. In metabolic engineering, CARs have been used to convert fatty acids and other carboxylic acids into aldehydes, which can be further transformed into alkanes, alcohols, and other chemicals. The reaction is highly specific for carboxylic acids and requires Mg2+ and ATP. Understanding the mechanism of CARs has enabled protein engineering efforts to improve their activity and substrate range for industrial applications [1,2].
Transport of Carboxylic Acids Across Membranes
In simple terms: Carboxylic acid transporters are proteins that move carboxylic acids into and out of cells.
Carboxylic acids are polar molecules that require specific transporters to cross biological membranes. In Candida species, carboxylic acid transporters are involved in the uptake of nutrients such as lactate, acetate, and pyruvate, which are important carbon sources. These transporters are also implicated in the efflux of antifungal drugs and in the regulation of intracellular pH. Studies have shown that carboxylic acid transporters in Candida albicans contribute to pathogenesis by enabling the fungus to acquire nutrients from host tissues and to survive in acidic environments. The expression of these transporters is regulated in response to carbon source availability and stress conditions. Targeting carboxylic acid transporters could be a strategy to combat fungal infections.
Metabolic Activation and Detoxification of Carboxylic Acids
In simple terms: Some carboxylic acids can be converted by enzymes into reactive forms that may damage cells, so the body has ways to detoxify them.
Metabolic activation of carboxylic acids often involves conjugation with coenzyme A (CoA) to form acyl-CoA thioesters, which can be reactive and disrupt cellular processes. For example, nonsteroidal anti-inflammatory drugs (NSAIDs) containing carboxylic acid groups can form acyl glucuronides that covalently bind to proteins, leading to toxicity. Similarly, valproic acid and other carboxylic acid drugs can undergo beta-oxidation to toxic metabolites. The body defends against these reactive species through conjugation with glutathione, glucuronic acid, or amino acids, and through efflux transporters. Understanding these pathways is crucial for predicting drug-induced liver injury and other adverse effects. Recent studies have also explored the metabolism of hydroxamic acid groups to carboxylic acids, which can occur via oxidation or hydrolysis, affecting drug stability and activity.
Signaling via Hydroxy-Carboxylic Acid Receptors
In simple terms: Certain carboxylic acids like lactate and beta-hydroxybutyrate can act as signals by binding to specific receptors on cells.
Hydroxy-carboxylic acid receptors (HCARs), including HCA1 (GPR81), HCA2 (GPR109A), and HCA3 (GPR109B), are G-protein-coupled receptors that are activated by endogenous carboxylic acids such as lactate, beta-hydroxybutyrate, and 3-hydroxyoctanoate. These receptors mediate diverse metabolic effects, including inhibition of lipolysis in adipocytes, regulation of immune cell function, and modulation of inflammation. For instance, HCA2 activation by beta-hydroxybutyrate or niacin reduces free fatty acid release and has anti-inflammatory effects. HCA1 is activated by lactate and may play a role in exercise-induced metabolic changes. These receptors are considered drug targets for dyslipidemia, atherosclerosis, and inflammatory diseases. Their discovery highlights the signaling roles of carboxylic acids beyond their traditional metabolic functions.
Environmental and Toxicological Aspects of Carboxylic Acids
In simple terms: Some man-made carboxylic acids, like certain PFAS chemicals, can enter the body and interfere with normal biology.
Hexafluoropropylene oxide trimer carboxylic acid (HFPO-TA) is a per- and polyfluoroalkyl substance (PFAS) that is used as a processing aid in fluoropolymer manufacture. It is a carboxylic acid that is highly persistent in the environment and has been detected in human blood. Studies in biological systems have shown that HFPO-TA can accumulate in the liver and affect lipid metabolism, possibly through interactions with peroxisome proliferator-activated receptors (PPARs). Its carboxylic acid moiety allows it to mimic natural fatty acids, disrupting metabolic pathways. Toxicological studies are ongoing to assess its health risks. This example illustrates how carboxylic acid metabolic process can be perturbed by environmental contaminants.
Key Genes Involved in GO:0019752 carboxylic acid metabolic process
The following genes and proteins are key players in carboxylic acid metabolic process, including enzymes, transporters, and receptors that have been characterized in the literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| CAR (various bacterial) | Carboxylic acid reductase; reduces carboxylic acids to aldehydes | Used in metabolic engineering for biofuel and chemical production [1,2] |
| HCA1 (GPR81) | Hydroxy-carboxylic acid receptor 1; activated by lactate | Mediates lactate signaling in adipose tissue and cancer |
| HCA2 (GPR109A) | Hydroxy-carboxylic acid receptor 2; activated by beta-hydroxybutyrate and niacin | Target for dyslipidemia and inflammation |
| HCA3 (GPR109B) | Hydroxy-carboxylic acid receptor 3; activated by 3-hydroxyoctanoate | Involved in immune regulation |
| Candida carboxylic acid transporters | Uptake and efflux of carboxylic acids | Virulence factors in Candida infections |
| UGT (UDP-glucuronosyltransferases) | Conjugation of carboxylic acids with glucuronic acid | Drug metabolism and detoxification |
| ACSM (acyl-CoA synthetases) | Activation of carboxylic acids to acyl-CoA thioesters | Metabolic activation and toxicity |
| CYP450 (various) | Oxidation of carboxylic acids | Drug metabolism and activation |
| ALDH (aldehyde dehydrogenases) | Oxidation of aldehydes to carboxylic acids | Detoxification and metabolism |
| ADH (alcohol dehydrogenases) | Reduction of aldehydes to alcohols or oxidation of alcohols to carboxylic acids | Metabolic pathways |
| PPARs (peroxisome proliferator-activated receptors) | Regulation of lipid metabolism genes | Target of PFAS carboxylic acids |
| MCT (monocarboxylate transporters) | Transport of lactate, pyruvate, and other carboxylic acids | Cancer metabolism and drug transport |
| FATP (fatty acid transport proteins) | Uptake of long-chain fatty acids | Metabolic disorders |
| ACAD (acyl-CoA dehydrogenases) | Beta-oxidation of fatty acids | Fatty acid oxidation disorders |
| CPT1 (carnitine palmitoyltransferase 1) | Transport of fatty acyl-CoA into mitochondria | Regulation of fatty acid oxidation |
| PDH (pyruvate dehydrogenase) | Conversion of pyruvate to acetyl-CoA | Central carbon metabolism |
| CS (citrate synthase) | Condensation of oxaloacetate and acetyl-CoA to citrate | TCA cycle |
| GLS (glutaminase) | Conversion of glutamine to glutamate | Cancer metabolism |
How Is carboxylic acid metabolic process Regulated?
Carboxylic acid metabolic process is regulated at multiple levels, including transcriptional control of genes encoding enzymes and transporters, post-translational modifications, and allosteric regulation by metabolites. For example, the expression of carboxylic acid transporters in Candida albicans is induced by the presence of specific carbon sources and regulated by stress-responsive transcription factors. In mammalian cells, hydroxy-carboxylic acid receptors are regulated by ligand availability and desensitization mechanisms. The activity of carboxylic acid reductases (CARs) is controlled by the availability of ATP and NADPH, and their expression can be engineered for optimal production in metabolic engineering [1,2]. Additionally, metabolic activation of carboxylic acids by acyl-CoA synthetases is regulated by the expression and activity of these enzymes, which can be induced by xenobiotics. Overall, the regulation of carboxylic acid metabolism ensures metabolic homeostasis and adaptation to environmental changes.
carboxylic acid metabolic process and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| HCA2 (GPR109A) | Dyslipidemia, inflammation | Knockout mouse, overexpression in adipocytes |
| Candida carboxylic acid transporters | Candidiasis, antifungal resistance | Candida albicans knockout strains, infection models |
| UGT1A1 | Drug-induced hyperbilirubinemia | Hepatocyte knock-in of UGT1A1 variants |
| MCAD | Medium-chain acyl-CoA dehydrogenase deficiency | MCAD knockout mouse, patient-derived fibroblasts |
| PPAR alpha | PFAS-induced hepatotoxicity | PPAR alpha knockout mouse, reporter assays |
Carboxylic Acid Metabolism in Cancer
Altered carboxylic acid metabolism is a hallmark of cancer. Cancer cells often exhibit increased glycolysis leading to lactate production, which is exported by monocarboxylate transporters (MCTs) and can signal through HCA1 to promote angiogenesis and immune evasion. Glutamine metabolism, which involves the conversion of glutamine to glutamate (a carboxylic acid) and then to alpha-ketoglutarate, supports biosynthetic needs and redox balance in cancer cells. Targeting these pathways, such as with glutaminase inhibitors, is an active area of cancer therapy. Additionally, fatty acid oxidation provides energy for cancer cells under metabolic stress. Thus, carboxylic acid metabolic process is deeply intertwined with cancer biology.
Carboxylic Acid Metabolism in Infectious Diseases
In pathogenic fungi such as Candida albicans, carboxylic acid transporters are essential for nutrient acquisition and virulence. These transporters enable the fungus to utilize lactate, acetate, and other carboxylic acids present in host niches, and they also contribute to drug resistance by effluxing azole antifungals. Therefore, inhibiting these transporters could be a novel antifungal strategy. In bacteria, carboxylic acid metabolism is also important for pathogenesis and survival in host environments. For example, Mycobacterium tuberculosis utilizes carboxylic acids as carbon sources during infection. Understanding these pathways may lead to new antimicrobial targets.
Carboxylic Acid Metabolism in Drug Toxicity
Many drugs contain carboxylic acid groups, and their metabolism can lead to reactive metabolites that cause toxicity. For instance, NSAIDs like diclofenac and ibuprofen form acyl glucuronides that can covalently modify proteins, leading to hepatotoxicity and hypersensitivity reactions. Valproic acid, an anticonvulsant, undergoes beta-oxidation and can produce toxic metabolites that contribute to hepatotoxicity and teratogenicity. The formation of acyl-CoA thioesters from carboxylic acid drugs can disrupt mitochondrial fatty acid oxidation, leading to steatosis and lactic acidosis. Understanding the metabolic activation of carboxylic acids is therefore critical in drug development to avoid adverse effects. Recent research has also focused on the metabolism of hydroxamic acid groups to carboxylic acids, which can affect drug stability and activity.
Carboxylic Acid Metabolism in Metabolic Disorders
Inherited deficiencies in enzymes involved in carboxylic acid metabolism can cause metabolic disorders. For example, medium-chain acyl-CoA dehydrogenase (MCAD) deficiency impairs fatty acid beta-oxidation, leading to accumulation of medium-chain carboxylic acids and episodes of hypoglycemia and coma. Similarly, defects in branched-chain amino acid metabolism, such as maple syrup urine disease, result in elevated levels of branched-chain keto acids (carboxylic acids) that are neurotoxic. These disorders highlight the importance of carboxylic acid metabolic process for normal physiology. Therapeutic strategies include dietary restriction and supplementation with carnitine to facilitate excretion of toxic acyl-CoA intermediates.
From carboxylic acid metabolic process-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of CAR enzyme affect carboxylic acid reduction in vivo? | Knockout of CAR gene in bacterial or yeast host |
| What is the effect of a point mutation in HCA2 on ligand binding? | Point mutation knock-in in cell lines (e.g., HEK293) |
| Can overexpression of a carboxylic acid transporter increase uptake? | Overexpression of transporter in Candida albicans or mammalian cells |
| How does a disease-associated variant in a metabolic enzyme alter flux? | Knock-in of mutant allele in patient-derived iPSCs |
| What is the subcellular localization of a carboxylic acid enzyme? | Tagged knock-in with fluorescent protein (e.g., GFP) |
| Which genes are essential for carboxylic acid metabolism in cancer? | CRISPR library screening in cancer cell lines |
How to Study the carboxylic acid metabolic process Process
| Method | What It Measures | Typical Application |
|---|---|---|
| LC-MS metabolomics | Levels of carboxylic acids and intermediates | Profiling metabolic changes in cells or tissues |
| 13C flux analysis | Metabolic flux through carboxylic acid pathways | Cancer metabolism, metabolic engineering |
| Enzyme activity assay | Catalytic activity of CARs or other enzymes | Characterization of wild-type and mutant enzymes |
| CRISPR knockout screen | Genes essential for growth on carboxylic acids | Identification of novel transporters or enzymes |
| Crystal structure | 3D structure of enzymes or transporters | Mechanistic studies and drug design |
| ITC/SPR | Binding affinity of carboxylic acids to proteins | Receptor-ligand interaction studies |
| Transport assay | Uptake or efflux of carboxylic acids | Characterization of transporters in Candida or mammalian cells |
| RNA-seq | Expression of genes in carboxylic acid metabolism | Transcriptional regulation studies |
Metabolomics and Flux Analysis
Metabolomics using mass spectrometry (LC-MS or GC-MS) is a powerful approach to profile carboxylic acids and their intermediates in biological samples. Targeted metabolomics can quantify specific carboxylic acids such as lactate, pyruvate, citrate, and fatty acids. Stable isotope-resolved metabolomics (SIRM) with 13C-labeled substrates allows tracing of metabolic fluxes through carboxylic acid pathways, revealing how cancer cells or engineered microbes utilize these compounds [1,5]. These methods are essential for understanding the dynamics of carboxylic acid metabolism in health and disease.
Enzyme Activity Assays
In vitro enzyme assays are used to measure the activity of carboxylic acid-metabolizing enzymes such as carboxylic acid reductases (CARs). These assays typically monitor the consumption of NADPH or ATP spectrophotometrically or the formation of aldehyde products using colorimetric or chromatographic methods [1,2]. For transporters, uptake assays with radiolabeled or fluorescent carboxylic acids can measure transport kinetics. Such assays are crucial for characterizing enzyme kinetics, substrate specificity, and the effects of inhibitors or mutations.
Genetic and CRISPR Screens
CRISPR-Cas9 knockout screens have been used to identify genes required for carboxylic acid metabolism and transport. For example, genome-wide screens in Candida albicans or cancer cells can reveal transporters or enzymes essential for growth on carboxylic acids as sole carbon sources. Similarly, CRISPR interference (CRISPRi) or activation (CRISPRa) can modulate gene expression to study metabolic pathways. These functional genomics approaches are powerful for discovering new players in carboxylic acid metabolic process.
Structural Biology and Biophysics
X-ray crystallography and cryo-electron microscopy have provided insights into the structure of carboxylic acid reductases and transporters, revealing their catalytic mechanisms and substrate binding sites. Isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR) can measure binding affinities of carboxylic acids to receptors or enzymes. These biophysical methods complement functional studies and aid in drug design targeting carboxylic acid metabolism [2,5].
How CRISPR Can Be Used to Study GO:0019752 carboxylic acid metabolic process
Knockout
CRISPR-Cas9 knockout is used to completely ablate genes involved in carboxylic acid metabolic process, such as carboxylic acid reductases, transporters, or receptors. For example, knocking out a carboxylic acid transporter in Candida albicans can reveal its role in nutrient uptake and virulence. In cancer cell lines, knockout of HCA1 or MCTs can assess their contribution to lactate signaling and tumor growth. Knockout models are essential for determining the necessity of a gene in a specific metabolic pathway.
Point Mutation
CRISPR-mediated point mutations (e.g., via homology-directed repair) allow the introduction of specific amino acid substitutions to study structure-function relationships. For instance, mutating the catalytic residues of a carboxylic acid reductase can confirm their role in catalysis. Similarly, point mutations in HCA2 that affect ligand binding can be introduced to understand receptor activation. These models are valuable for dissecting molecular mechanisms without completely eliminating protein expression.
Knock-in
Knock-in of reporter genes or tags (e.g., GFP, FLAG) at endogenous loci enables visualization and purification of proteins involved in carboxylic acid metabolism. For example, tagging a carboxylic acid transporter with GFP allows tracking its localization and dynamics in live cells. Knock-in of disease-associated variants (e.g., in UGT1A1) can model drug metabolism phenotypes. This approach preserves endogenous regulation and provides physiological relevance.
Overexpression
CRISPR activation (CRISPRa) or traditional overexpression via lentiviral vectors can increase the expression of genes in carboxylic acid metabolism. Overexpressing a carboxylic acid reductase in a microbial host can enhance production of aldehydes for industrial applications. In mammalian cells, overexpression of HCA2 can amplify signaling responses to beta-hydroxybutyrate. Overexpression models are useful for gain-of-function studies and biotechnological applications.
How EDITGENE Supports carboxylic acid metabolic process Research
Researchers studying carboxylic acid metabolic process-related genes often need to determine whether a candidate gene is causally involved in a specific metabolic pathway, disease, or biotechnological trait. This requires precise genetic manipulation, which can be achieved through CRISPR-based knockout, point mutation, knock-in, or overexpression. EDITGENE provides comprehensive services to generate these models efficiently and reliably, enabling mechanistic studies and target validation.
Contact EDITGENE today to design your custom CRISPR model for carboxylic acid metabolic process research.
Frequently Asked Questions About carboxylic acid metabolic process
What is carboxylic acid metabolic process?
Carboxylic acid metabolic process (GO:0019752) is the set of chemical reactions and pathways involving carboxylic acids, which are organic acids containing one or more carboxyl (COOH) groups or their anions (COO-). This includes their synthesis, breakdown, and interconversion [1,4].
What genes are involved in carboxylic acid metabolic process?
Genes encoding carboxylic acid reductases (CARs), hydroxy-carboxylic acid receptors (HCA1, HCA2, HCA3), carboxylic acid transporters, acyl-CoA synthetases, UDP-glucuronosyltransferases, and various oxidoreductases are involved [1,2,3,4,5].
How is carboxylic acid metabolic process regulated?
It is regulated at transcriptional, post-translational, and allosteric levels. For example, carboxylic acid transporters in Candida are induced by carbon source availability, and CAR activity depends on ATP and NADPH [1,3].
What diseases are associated with defects in carboxylic acid metabolism?
Defects can cause metabolic disorders such as medium-chain acyl-CoA dehydrogenase deficiency, drug-induced toxicity, and may contribute to cancer and infectious diseases [3,4,5].
What is the role of carboxylic acid reductases in biotechnology?
Carboxylic acid reductases (CARs) convert carboxylic acids to aldehydes, which are valuable for producing biofuels, pharmaceuticals, and other chemicals in engineered microbes [1,2].
How can I study carboxylic acid metabolic process in the lab?
Common methods include metabolomics (LC-MS), enzyme activity assays, CRISPR knockout screens, and structural biology. These approaches allow profiling of metabolites, measuring enzyme kinetics, and identifying essential genes [1,2,3].
What are hydroxy-carboxylic acid receptors?
HCA1 (GPR81), HCA2 (GPR109A), and HCA3 (GPR109B) are G-protein-coupled receptors activated by endogenous carboxylic acids like lactate and beta-hydroxybutyrate, mediating metabolic and inflammatory effects.
Why is carboxylic acid metabolism important in drug development?
Many drugs contain carboxylic acid groups, and their metabolism can produce reactive metabolites that cause toxicity. Understanding these pathways helps predict and mitigate adverse drug reactions [4,6].
What is the connection between carboxylic acid metabolism and cancer?
Cancer cells often rely on altered carboxylic acid metabolism, such as increased lactate production and glutamine utilization, to support growth and survival. Targeting these pathways is a therapeutic strategy.
How does EDITGENE support research on carboxylic acid metabolic process?
EDITGENE provides CRISPR knockout, point mutation, knock-in, overexpression cell models, and CRISPR library screening services to study genes involved in carboxylic acid metabolism, enabling mechanistic and target validation studies.
Conclusion
Carboxylic acid metabolic process (GO:0019752) is a fundamental biological process that encompasses the metabolism of carboxylic acids, which are central to energy production, biosynthesis, and signaling. From microbial metabolic engineering to human disease, understanding the enzymes, transporters, and receptors involved is crucial. The integration of CRISPR-based genetic models with metabolomics and structural biology continues to advance our knowledge of this pathway. EDITGENE offers a comprehensive suite of services to facilitate research in this field, helping scientists uncover new insights and develop novel therapeutics.
References
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- 2. Gahloth D et al.. 2020. Carboxylic acid reductase: Structure and mechanism.. J Biotechnol 307:107-113 PMID: 31689469
- 3. Alves R et al.. 2020. Carboxylic Acid Transporters in Candida Pathogenesis.. mBio 11(3) PMID: 32398310
- 4. Skonberg C et al.. 2008. Metabolic activation of carboxylic acids.. Expert Opin Drug Metab Toxicol 4(4):425-38 PMID: 18433345
- 5. Offermanns S. 2017. Hydroxy-Carboxylic Acid Receptor Actions in Metabolism.. Trends Endocrinol Metab 28(3):227-236 PMID: 28087125
- 6. Huang X et al.. 2025. Mechanism of hydroxamic acid group metabolism to carboxylic acid: Oxidation versus hydrolysis.. Drug Metab Dispos 53(10):100151 PMID: 40974980
- 8. Yang B et al.. 2025. Hexafluoropropylene Oxide Trimer Carboxylic Acid in Biological Systems.. Basic Clin Pharmacol Toxicol 137(5):e70117 PMID: 41014205
