Adipic Acid
Adipic acid is a dicarboxylic acid, characterized by the presence of two carboxyl functional groups. While primarily recognized for its extensive use in industrial applications, particularly in the synthesis of nylon, it also functions as an endogenous metabolite within the human body.
Biological Basis
Section titled “Biological Basis”Within biological systems, adipic acid serves as an intermediate compound in several metabolic pathways. It can be formed through the omega-oxidation of fatty acids, a process that may become more active under certain physiological conditions, such as impaired beta-oxidation. Additionally, adipic acid can be generated from the catabolism of specific amino acids, including lysine. Its presence in human plasma and urine reflects ongoing metabolic activity. The comprehensive of endogenous metabolites, including adipic acid, in bodily fluids is a key aspect of metabolomics studies, which aim to provide a functional readout of an individual’s physiological state.[1]
Clinical Relevance
Section titled “Clinical Relevance”The assessment of adipic acid levels carries clinical importance, particularly as a potential biomarker for certain metabolic disorders. Elevated concentrations of adipic acid in urine, for instance, can be indicative of inborn errors of metabolism affecting fatty acid oxidation, such as Medium-chain acyl-CoA dehydrogenase deficiency (MCADD), where the body’s ability to break down medium-chain fatty acids is compromised. Such measurements are often incorporated into newborn screening programs. Beyond diagnostic applications, adipic acid levels can be influenced by dietary intake, the composition of the gut microbiota, and overall metabolic health. Research utilizing genome-wide association studies (GWAS) to analyze metabolite profiles, including adipic acid, helps in identifying genetic variants that influence the homeostasis of various biomolecules, thereby offering new perspectives on disease mechanisms.[1]
Social Importance
Section titled “Social Importance”Accurate and interpretation of adipic acid levels, especially when integrated with genetic information, significantly advance the understanding of individual metabolic health. This knowledge can contribute to the development of personalized medicine strategies, enable the early detection of metabolic conditions, and support the creation of targeted therapeutic interventions. By establishing connections between genetic variants and metabolite profiles, research in this field provides a comprehensive view of the human body’s physiological state, with broad implications for public health, disease prevention, and the formulation of new treatment approaches.[1]
Methodological and Statistical Considerations
Section titled “Methodological and Statistical Considerations”Studies often face limitations due to sample size, which can restrict the statistical power to detect genetic effects, especially for variants with modest contributions to the adipic acid phenotype.[2] While meta-analyses combine data across cohorts to increase power, individual study designs and varying demographics can introduce heterogeneity that complicates interpretation.[3]The inability to consistently replicate all findings, where SNP replication can be equivocal, highlights the need for larger, more diverse datasets to confirm associations and prevent potential effect-size inflation.[4]Methodological differences in assays used across studies, along with varying demographic profiles, can lead to discrepancies in measured adipic acid levels, affecting comparability.[3] Furthermore, the reliance on genotype imputation, while enhancing coverage, introduces a degree of uncertainty, particularly in regions with a lack of high-quality imputation, which may impact the accuracy of identified genetic associations.[3] These factors necessitate careful consideration when interpreting the strength and consistency of reported genetic signals.
Generalizability and Phenotype Definition
Section titled “Generalizability and Phenotype Definition”A significant limitation arises from the predominant reliance on cohorts of European ancestry, including specific groups like those from Sardinia, Finland, and Sweden.[5] The exclusion of individuals of non-European ancestry from analyses restricts the generalizability of findings, as genetic architecture and allele frequencies can vary substantially across different populations.[6] This lack of diversity means that the identified genetic variants may not be equally relevant or impactful in other ethnic groups, limiting the broader applicability of the research.
The accurate and consistent definition of adipic acid levels as a phenotype presents challenges. Factors such as fasting status prior to blood collection and the use of medications (e.g., lipid-lowering therapies, which were often exclusions) can significantly influence metabolite concentrations.[4] Averaging measurements across multiple examinations or relying on potentially imprecise assays introduces variability, which can obscure true genetic effects or lead to inconsistent associations, necessitating rigorous standardization protocols for future studies.[2]
Environmental and Gene-Environment Interactions
Section titled “Environmental and Gene-Environment Interactions”The influence of environmental factors on adipic acid levels and their interaction with genetic predispositions represents a substantial, often unexplored, limitation. Genetic variants can influence phenotypes in a context-specific manner, with their effects modulated by various environmental influences, such as diet or lifestyle, which are frequently not investigated in detail.[2]For example, specific dietary components could significantly alter adipic acid metabolism, potentially masking or modifying genetic associations.
Despite identifying numerous genetic loci, a considerable portion of the variance in complex traits like adipic acid levels remains unexplained, pointing to the concept of missing heritability.[4] The current research often does not undertake comprehensive investigations of gene-environment interactions, leaving significant gaps in understanding the full biological mechanisms and the interplay between genetic and environmental factors.[2]Addressing these complex interactions is crucial for a complete understanding of adipic acid metabolism and its clinical implications.
Variants
Section titled “Variants”Genetic variations play a crucial role in influencing an individual’s metabolic profile, including levels of various metabolites like adipic acid. The variants discussed here are associated with genes involved in fundamental cellular processes, energy metabolism, and epigenetic regulation, all of which can indirectly or directly impact metabolic pathways. While adipic acid is a dicarboxylic acid often associated with fatty acid oxidation, the genes linked to these single nucleotide polymorphisms (SNPs) highlight broader metabolic connections.
Several variants are associated with genes or pseudogenes involved in gene expression and cellular signaling. For example, rs10970184 is linked to CARM1P1, a pseudogene of CARM1(Coactivator-associated arginine methyltransferase 1), which plays a significant role in chromatin remodeling and regulating the expression of metabolic genes.[7] Similarly, rs1486618 is found near THAP12P9, another pseudogene, whose active counterpart, THAP12, is involved in DNA binding and transcriptional control, impacting overall cellular function and energy balance.[1] The variant rs11196730 is associated with AFAP1L2(Actin Filament Associated Protein 1 Like 2), a gene crucial for cytoskeletal organization and intracellular signaling. These basic cellular mechanisms are essential for how cells respond to nutrient availability and regulate metabolic pathways, potentially influencing the production or breakdown of metabolites like adipic acid.
Other variants are associated with enzymes or transport proteins that directly or indirectly influence metabolic processes. The rs12623145 variant is linked to DPP10 (Dipeptidyl Peptidase 10), a member of a family of enzymes that process peptides. While DPP10itself may not be a primary metabolic enzyme, the broader dipeptidyl peptidase family is known to affect hormone signaling and nutrient processing, which are central to metabolic regulation and can influence traits like diabetes.[8] Another variant, rs6779362 , is associated with MELTF(Melanotransferrin), an iron-binding protein. Iron metabolism is fundamental to mitochondrial function and energy production, as iron is a critical component of many enzymes in the electron transport chain, thereby affecting the efficiency of fatty acid oxidation and potentially adipic acid levels.[9] Variants impacting mitochondrial function and epigenetic regulation can have profound effects on metabolism. For instance, rs11657766 is located near COX10-DT, a divergent transcript associated with COX10 (Cytochrome c oxidase assembly factor 10). COX10 is vital for assembling cytochrome c oxidase, a key enzyme in the mitochondrial respiratory chain that is essential for cellular energy production. Impaired mitochondrial function due to variations in COX10or its regulatory elements could directly affect fatty acid oxidation, a pathway relevant to adipic acid levels.[1] The variant rs10975861 is linked to KDM4C(Lysine Demethylase 4C), a histone demethylase involved in epigenetic regulation of gene expression. Epigenetic mechanisms are known to control the expression of genes involved in adipogenesis, insulin sensitivity, and lipid metabolism, which are all interconnected with the production of various metabolites.[7] Finally, rs1465549 is associated with GLULP5 and LINC02459. GLULP5 is a pseudogene of GLUL(Glutamine synthetase), an enzyme central to nitrogen and amino acid metabolism, which also plays a role in energy homeostasis.LINC02459is a long non-coding RNA, often involved in regulating gene expression, and its variations could influence metabolic pathways that affect adipic acid concentrations or related adiposity traits.[10]
Key Variants
Section titled “Key Variants”Biochemical Profiling and Metabolic Assessment
Section titled “Biochemical Profiling and Metabolic Assessment”Diagnosis involving metabolic traits often commences with comprehensive biochemical profiling, which aims to identify specific “biochemical phenotypes” within an individual’s “metabolite profiles in human serum”.[1]These profiles are generated through various laboratory techniques, providing a snapshot of metabolic status and aiding in the identification of disruptions. For instance, methods such as spectrophotometry are utilized for measuring liver enzymes like γ-glutamyl aminotransferase, while colorimetric assays are employed for bilirubin, and ELISA kits for plasma adiponectin and resistin.[11]Similarly, enzymatic-colorimetric methods are common for assessing serum uric acid, and glucose dehydrogenase methods for blood glucose.[12] Such detailed biochemical assessments are crucial for diagnosing conditions related to “fatty acid metabolism,” where specific metabolic markers can indicate underlying disorders.[13] The correlation of these biochemical phenotypes with known conditions, such as “medium-chain acyl-CoA dehydrogenase deficiency,” allows clinicians to identify metabolic dysregulation through the detection of characteristic metabolite patterns.[14] The accuracy of these assays is maintained through standardized protocols and quality control measures, ensuring reliable diagnostic data.
Genetic and Molecular Diagnostics
Section titled “Genetic and Molecular Diagnostics”Genetic testing plays a pivotal role in confirming metabolic disorders and understanding their underlying molecular basis. Genome-wide association studies (GWAS) are instrumental in identifying common genetic variants in specific genomic regions that influence various traits and disease risks.[15] For instance, in the context of “medium-chain acyl-CoA dehydrogenase deficiency,” the correlation between specific ACADM genotypes and observed biochemical phenotypes is a key diagnostic approach, providing definitive genetic confirmation of the condition.[14] Molecular markers identified through these genetic analyses complement biochemical findings by revealing genetic predispositions or direct genetic causes of metabolic imbalances. This integrated approach allows for a precise diagnosis, distinguishing between phenotypically similar conditions and guiding personalized management strategies. The consistent nominal associations of SNPs with multiple related traits further enhance the utility of genetic information in diagnosing complex metabolic conditions.
Screening and Clinical Evaluation
Section titled “Screening and Clinical Evaluation”Population-based screening methods are essential for the early detection of metabolic disorders, particularly in vulnerable populations. A notable example is “newborn screening for medium-chain acyl-CoA dehydrogenase deficiency,” which relies on the identification of specific “biochemical phenotypes” in infants.[14] Such early screening programs are critical for prompt diagnosis and intervention, significantly improving patient outcomes by preventing severe clinical manifestations before symptoms appear.
While detailed physical examination findings for specific metabolic conditions are not extensively described, a thorough clinical evaluation remains fundamental. This involves gathering a comprehensive patient history, assessing symptoms, and performing a physical examination to guide the selection and interpretation of specialized laboratory and genetic tests. The integration of clinical findings with objective biochemical and genetic evidence is paramount for accurate diagnosis, allowing clinicians to differentiate the condition from other similar presentations and formulate an effective treatment plan.
Regulation of Fatty Acid and Lipid Metabolism
Section titled “Regulation of Fatty Acid and Lipid Metabolism”The human body intricately regulates the synthesis, breakdown, and modification of fatty acids and lipids to maintain cellular function and energy balance. Key enzymes, such as the fatty acid delta-5 desaturase encoded by the FADS1 gene, are crucial for producing long-chain polyunsaturated fatty acids from essential precursors like linoleic acid.[1] These metabolic pathways are fundamental for the production of various lipid classes, including phospholipids, which are vital components of cell membranes.[16] Disruptions in these processes, such as deficiencies in medium-chain acyl-CoA dehydrogenase (ACADM), can impair the efficient breakdown of fatty acids, leading to observable biochemical phenotypes.[14] Comprehensive of endogenous metabolites, known as metabolomics, provides a functional readout of the physiological state, revealing how these intricate pathways are operating within the body.[1]
Genetic Determinants of Lipid Homeostasis
Section titled “Genetic Determinants of Lipid Homeostasis”Genetic variations play a significant role in influencing an individual’s lipid profile and overall metabolic health. Genome-wide association studies (GWAS) have identified numerous genetic loci and specific genes that impact circulating levels of various lipids, including high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), and triglycerides.[6] For example, variants near the HMGCR gene, which encodes 3-hydroxy-3-methylglutaryl-CoA reductase, a rate-limiting enzyme in cholesterol synthesis, have been associated with LDL-cholesterol levels and can affect the alternative splicing of its exon 13.[17] Similarly, the APOC3gene, involved in triglyceride metabolism, has been found to harbor null mutations that lead to a favorable plasma lipid profile due to diminished very low-density lipoprotein (VLDL) fractional catabolic rates.[18] Other genes, such as LIPC (hepatic lipase) and MLXIPL(MLX interacting protein like), also contribute to the genetic architecture of lipid levels, with variations affecting their expression or function and consequently influencing triglyceride and other lipid concentrations.[6], [19]
Systemic Lipid Dynamics and Health Implications
Section titled “Systemic Lipid Dynamics and Health Implications”The intricate balance of lipid metabolism at the cellular and molecular levels has profound systemic consequences, affecting various tissues and organs, particularly the liver and adipose tissue. Dysregulation in these pathways can lead to homeostatic disruptions that manifest as clinical conditions such as dyslipidemia, non-alcoholic fatty liver disease (NAFLD), and an increased risk of cardiovascular disease.[6] For instance, elevated serum levels and hepatic mRNA expression of GPLD1 (glycosylphosphatidylinositol specific phospholipase D1), an enzyme that releases GPI-anchored proteins from cell membranes, have been reported in NAFLD.[3]Beyond lipids, the overall metabolic state of an individual is reflected in various biomarkers, including liver enzymes like gamma-glutamyl aminotransferase and alkaline phosphatase, and hormones such as adiponectin and resistin, which are often measured to assess metabolic health and disease risk.[8], [11]These systemic markers provide valuable insights into the complex interplay between genetic predispositions, environmental factors, and the overall physiological state that influences circulating adipic acid levels and related metabolic profiles.
Metabolic Pathways and Lipid Homeostasis
Section titled “Metabolic Pathways and Lipid Homeostasis”The levels of metabolites like adipic acid are intricately linked to core metabolic pathways, particularly those involved in lipid and energy metabolism. Comprehensive analysis of endogenous metabolites, known as metabolomics, aims to provide a functional readout of the physiological state, revealing how genetic variants influence the homeostasis of key lipids, carbohydrates, or amino acids.[1] Fatty acid metabolism is a crucial component, where enzyme clusters like FADS1 and FADS2play a significant role in determining the composition of fatty acids, including polyunsaturated fatty acids like arachidonic acid, in phospholipids.[1] These enzymes are essential for the synthesis of long-chain poly-unsaturated fatty acids from essential fatty acids, demonstrating the flux control within these pathways.[1] Beyond fatty acid synthesis, catabolic processes are equally vital, as exemplified by medium-chain acyl-CoA dehydrogenase deficiency, which highlights the importance of acyl-CoA dehydrogenases in breaking down fatty acids.[1] Furthermore, the mevalonate pathway, regulated by enzymes like 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), controls cholesterol biosynthesis, a fundamental aspect of lipid metabolism.[20] The efficiency of these enzymatic reactions and the balance between biosynthesis and catabolism are critical determinants of metabolite concentrations, shaping the overall lipid profile and influencing cellular energy status.[1]
Genetic and Post-Translational Regulation
Section titled “Genetic and Post-Translational Regulation”The cellular levels of enzymes and transporters that govern metabolite concentrations are tightly controlled through various regulatory mechanisms, including gene regulation and post-translational modifications. For instance, the adiponutringene, which influences lipid metabolism, is regulated by insulin and glucose in human adipose tissue, and variations in this gene can impact its expression and associate with conditions like obesity.[3]Genetic variants can also exert their effects by altering pre-mRNA splicing, as seen with common single nucleotide polymorphisms (SNPs) inHMGCR that affect the alternative splicing of exon 13, consequently influencing LDL-cholesterol levels.[17] Beyond transcriptional and splicing control, proteins undergo modifications that regulate their activity and stability. The degradation rate of enzymes like 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) is influenced by its oligomerization state, suggesting a form of post-translational regulation.[21] Additionally, allosteric control mechanisms, where molecules bind to an enzyme at a site other than the active site to alter its activity, contribute to metabolic regulation, ensuring that pathway flux responds dynamically to cellular needs and substrate availability.[22]
Signaling and Intercellular Communication
Section titled “Signaling and Intercellular Communication”Metabolite levels are also influenced by complex signaling pathways that mediate cellular responses to external cues and internal states. Receptor activation, such as the interaction of proteins with the thyroid hormone receptor, can depend on the presence or absence of specific hormones, initiating cascades that regulate gene expression and metabolic processes.[23] Intracellular signaling cascades involve proteins like Pleckstrin, which associates with plasma membranes and induces membrane projections, a process requiring phosphorylation and its NH2-terminal PH domain, highlighting the role of protein modification in signal transduction.[24] These signaling events often converge on transcription factors, which then regulate the expression of genes involved in metabolic pathways. For example, the regulation of the adiponutringene by insulin and glucose implies the involvement of such cascades that modulate transcription factor activity.[3] Furthermore, feedback loops are integral to maintaining metabolic balance; for instance, the regulation of the mevalonate pathway by cholesterol levels serves as a classic example of how end-products can modulate earlier steps in their own synthesis, preventing overproduction and maintaining homeostasis.[20]
Pathway Interconnections and Systemic Impact
Section titled “Pathway Interconnections and Systemic Impact”Metabolic pathways do not operate in isolation but are highly interconnected, forming complex networks that exhibit emergent properties critical for systemic physiological function. The field of metabolomics, by measuring comprehensive metabolite profiles, helps to uncover these network interactions and pathway crosstalk, demonstrating how genetic variants can impact the homeostasis of various key biomolecules.[1] Analyzing ratios of metabolite concentrations, such as direct substrates and products of an enzymatic reaction, can significantly reduce data variation and reveal the efficiency of specific enzymatic steps, providing insights into pathway flux and control.[1]This systems-level integration highlights how alterations in one pathway can ripple through the entire metabolic network, influencing distant processes. For example, the interplay between lipid metabolism and glucose/insulin signaling, as evidenced by the regulation of theadiponutrin gene, illustrates how these pathways communicate to maintain systemic energy balance.[3] The collective effect of these interacting pathways contributes to the overall metabolic phenotype, which serves as a functional readout of the human body’s physiological state.[1]
Dysregulation in Disease States
Section titled “Dysregulation in Disease States”Dysregulation of these intricate metabolic and signaling pathways is frequently implicated in various disease states, leading to altered metabolite profiles. For example, glycosylphosphatidylinositol-specific phospholipase D has been observed in nonalcoholic fatty liver disease, indicating a specific enzymatic dysregulation contributing to hepatic lipid accumulation.[25] Similarly, dyslipidemia, characterized by abnormal lipid concentrations, is influenced by common genetic variants at multiple loci, highlighting the polygenic nature of metabolic disorders.[9]Understanding these pathway dysregulations can identify potential therapeutic targets and mechanisms for disease intervention. For instance, theHMGCR enzyme, central to cholesterol synthesis, is a well-established target for lipid-lowering therapies.[17] Genetic studies linking variants in genes like SLC2A9 (also known as GLUT9) to serum uric acid levels demonstrate how specific transporters contribute to metabolic disorders like gout and metabolic syndrome.[1]These insights into the molecular underpinnings of disease-relevant mechanisms are crucial for developing targeted treatments and understanding compensatory responses within the body.[1]
Frequently Asked Questions About Adipic Acid
Section titled “Frequently Asked Questions About Adipic Acid”These questions address the most important and specific aspects of adipic acid based on current genetic research.
1. Can eating certain foods impact my adipic acid numbers?
Section titled “1. Can eating certain foods impact my adipic acid numbers?”Yes, what you eat can definitely influence your adipic acid levels. While adipic acid is produced naturally in your body, your dietary intake can affect the metabolic pathways that produce or break it down, leading to changes in its concentration.
2. Why would a newborn screening check my baby’s adipic acid?
Section titled “2. Why would a newborn screening check my baby’s adipic acid?”Newborn screening often checks adipic acid as a vital marker for specific metabolic disorders. Elevated levels can indicate conditions like Medium-chain acyl-CoA dehydrogenase deficiency (MCADD), where the body struggles to break down fats, making early detection crucial for intervention.
3. Could my body’s fat breakdown issues raise my adipic acid?
Section titled “3. Could my body’s fat breakdown issues raise my adipic acid?”Yes, if your body has difficulty breaking down fatty acids through its usual pathways, such as impaired beta-oxidation, it might activate alternative metabolic routes. These alternative pathways can lead to an increase in adipic acid production, causing higher levels.
4. Does my gut bacteria influence my adipic acid levels?
Section titled “4. Does my gut bacteria influence my adipic acid levels?”Absolutely, the composition of your gut microbiota can play a role in your adipic acid levels. Your gut bacteria interact with many metabolic processes, and their specific balance can influence how your body produces or processes various metabolites, including adipic acid.
5. Could my family history explain my adipic acid levels?
Section titled “5. Could my family history explain my adipic acid levels?”Yes, genetics play a significant role in determining your adipic acid levels. Research has identified specific genetic variants that influence how your body metabolizes this compound, meaning tendencies for certain levels can be inherited through your family.
6. What would a personal adipic acid test tell me about my health?
Section titled “6. What would a personal adipic acid test tell me about my health?”A personal adipic acid test could offer valuable insights into your metabolic health. It can serve as a biomarker, potentially indicating underlying metabolic disorders or providing a functional readout of your body’s current physiological state, which can inform personalized health strategies.
7. Does my ancestry affect what’s ‘normal’ for my adipic acid?
Section titled “7. Does my ancestry affect what’s ‘normal’ for my adipic acid?”Yes, it’s possible. Much of the research on genetic influences on metabolites like adipic acid has focused on populations of European ancestry. Genetic architecture and allele frequencies can vary significantly across different ethnic groups, meaning what’s considered a ‘normal’ range might differ for you based on your ancestry.
8. Could my current medications change my adipic acid test?
Section titled “8. Could my current medications change my adipic acid test?”Yes, certain medications can significantly influence your adipic acid levels. For instance, some lipid-lowering therapies have been shown to affect metabolite concentrations. It’s always important to inform your doctor about any medications you are taking when interpreting test results.
9. Does fasting matter for my adipic acid test results?
Section titled “9. Does fasting matter for my adipic acid test results?”Yes, fasting status prior to blood collection can definitely influence your adipic acid concentrations. To ensure the most accurate and comparable results, rigorous standardization protocols, including fasting, are often necessary for these types of metabolic measurements.
10. Could adipic acid levels show something about my overall health?
Section titled “10. Could adipic acid levels show something about my overall health?”Yes, adipic acid levels are considered a reflection of ongoing metabolic activity and overall metabolic health. As part of metabolomics studies, measuring endogenous metabolites like adipic acid provides a functional readout of your physiological state, offering clues about your body’s internal processes.
This FAQ was automatically generated based on current genetic research and may be updated as new information becomes available.
Disclaimer: This information is for educational purposes only and should not be used as a substitute for professional medical advice. Always consult with a healthcare provider for personalized medical guidance.
References
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[12] Li, S. et al. “The GLUT9 gene is associated with serum uric acid levels in Sardinia and Chianti cohorts.”PLoS Genet (2007).
[13] Caspi, A., et al. “Moderation of breastfeeding effects on the IQ by genetic variation in fatty acid metabolism.” Proc Natl Acad Sci U S A, vol. 104, 2007, pp. 18860–18865.
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[15] Dehghan, A., et al. “Association of three genetic loci with uric acid concentration and risk of gout: a genome-wide association study.”Lancet, vol. 372, 2008, pp. 1823-1831.
[16] Vance, J. E. “Membrane lipid biosynthesis.” Encyclopedia of Life Sciences, John Wiley & Sons, Ltd, 2001.
[17] Burkhardt, R. et al. “Common SNPs in HMGCR in micronesians and whites associated with LDL-cholesterol levels affect alternative splicing of exon13.” Arterioscler Thromb Vasc Biol (2008).
[18] Pollin, T. I., et al. “A null mutation in human APOC3 confers a favorable plasma lipid profile and apparent cardioprotection.” Science, 2008.
[19] Kooner, J. S., et al. “Genome-wide scan identifies variation in MLXIPL associated with plasma triglycerides.” Nature Genetics, 2008.
[20] Goldstein, J.L. et al. “Regulation of the mevalonate pathway.” Nature (1990).
[21] Cheng, H.H. et al. “Oligomerization state influences the degradation rate of 3-hydroxy-3-methylglutaryl-CoA reductase.” J Biol Chem (1999).
[22] Istvan, E.S. et al. “Crystal structure of the catalytic portion of human HMG-CoA reductase: insights into regulation of activity and catalysis.” Embo J (2000).
[23] Lee, J.W. et al. “Two classes of proteins dependent on either the presence or absence of thyroid hormone for interaction with the thyroid hormone receptor.”Mol. Endocrinol. (1995).
[24] Ma, A.D. et al. “Pleckstrin associates with plasma membranes and induces the formation of membrane projections: requirements for phosphorylation and the NH2-terminal PH domain.” J Cell Biol (1997).
[25] Chalasani, N. et al. “Glycosylphosphatidylinositol-specific phospholipase d in nonalcoholic Fatty liver disease: A preliminary study.”J. Clin. Endocrinol. Metab. (2006).